Bacillus Calmette-Guérin vaccination, thymic size, and thymic output in healthy newborns

DEFF Research Database (Denmark)

Birk, Nina Marie; Nissen, Thomas Nørrelykke; Zingmark, Vera

2017-01-01

BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size...... to age 3 mo were parent-reported. RESULTS: BCG vaccination did not affect thymic size at age 3 mo, measured as TI. At birth, the number of lymphocytes, CD4+ T cells, CD8+ T cells, and RTEs were positively associated with TI and TWI. Furthermore, a reduced risk of infections up to age 3 mo was associated...... with a large thymic size at birth. CONCLUSION: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity...

Significance of thymic scintigraphy

International Nuclear Information System (INIS)

Baba, Hiromi; Oshiumi, Yoshihiko; Nakayama, Chikashi; Morita, Kazunori; Koga, Ichinari

1978-01-01

Thymic scintigraphy by 67 Ga-citrate and 75 Se-methionine was done on 6 cases of thymoma, and 5 cases of myasthenia gravis. Scan was positive on 5 of 6 cases of thymoma. All patients with malignant thymoma were positive. Among the 7 cases of myasthenia gravis, scintigrams revealed 2 thymomas and 1 hyperplasia on whom no thymic mass suspected. Thymic scintigraphy is useful examination when dealing with myasthenia gravis. (auth.)

Three cases of unresectable locally advanced breast cancer treated with local injection of the new radiosensitization (KORTUC)

International Nuclear Information System (INIS)

Shimbo, Taijyu; Yosikawa, Nobuhiko; Yoshioka, H.; Tanaka, Y.; Yoshida, Ken; Uesugi, Yasuo; Narumi, Yoshifumi; Inomata, Taisuke

2013-01-01

New radiosensitization therapy named Kochi Oxydol-Radiation Therapy for Unresectabe carcinomas (KORTUC) using a new agent containing 0.5% hydrogen peroxide and 0.83% sodium hyaluronate is the world first treatment developed in Japan. The agent was injected into tumor two times per week under ultrasonographic guidance. Unresectable locally advanced breast cancer is radiation resistance. The local control is difficult in a conventional radiation therapy. In 3 cases, KORTUC was enforced safety, and remarkable effects was admitted. (author)

Images in pediatrics: the thymic sail sign and thymic wave sign.

Science.gov (United States)

Alves, Nuno D; Sousa, Marta

2013-01-01

The authors present a radiographic image portraying the "thymic sail sign" and the "thymic wave sign," both normal findings in infant radiographs and present a short description of these signs. These are distinguished from pathologic findings such as the "spinnaker-sail sign" in pneumomediastinum.

A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer.

Science.gov (United States)

Gupta, Arunima; Roy, Somnath; Majumdar, Anup; Hazra, Avijit; Mallik, Chandrani

2014-01-01

Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m(-2) intravenously on day 1 and 5-fluorouracil (1000 mg m(-2) continuous intravenous infusion on days 1-4 starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions.

Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Sudo, Kentaro; Yamaguchi, Taketo; Ishihara, Takeshi; Nakamura, Kazuyoshi; Shirai, Yoshihiko; Nakagawa, Akihiko; Kawakami, Hiroyuki; Uno, Takashi; Ito, Hisao; Saisho, Hiromitsu

2007-01-01

Purpose: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m 2 /day. Results: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m 2 /day, 3 at 70 mg/m 2 /day, and 10 at 80 mg/m 2 /day. Though 1 patient at the final dose level (80 mg/m 2 /day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. Conclusions: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m 2 /day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated

PPARgamma Deficiency Counteracts Thymic Senescence

Directory of Open Access Journals (Sweden)

David Ernszt

2017-11-01

Full Text Available Thymic senescence contributes to increased incidence of infection, cancer and autoimmunity at senior ages. This process manifests as adipose involution. As with other adipose tissues, thymic adipose involution is also controlled by PPARgamma. This is supported by observations reporting that systemic PPARgamma activation accelerates thymic adipose involution. Therefore, we hypothesized that decreased PPARgamma activity could prevent thymic adipose involution, although it may trigger metabolic adverse effects. We have confirmed that both human and murine thymic sections show marked staining for PPARgamma at senior ages. We have also tested the thymic lobes of PPARgamma haplo-insufficient and null mice. Supporting our working hypothesis both adult PPARgamma haplo-insufficient and null mice show delayed thymic senescence by thymus histology, thymocyte mouse T-cell recombination excision circle qPCR and peripheral blood naive T-cell ratio by flow-cytometry. Delayed senescence showed dose–response with respect to PPARgamma deficiency. Functional immune parameters were also evaluated at senior ages in PPARgamma haplo-insufficient mice (null mice do not reach senior ages due to metabolic adverse affects. As expected, sustained and elevated T-cell production conferred oral tolerance and enhanced vaccination efficiency in senior PPARgamma haplo-insufficient, but not in senior wild-type littermates according to ELISA IgG measurements. Of note, humans also show increased oral intolerance issues and decreased protection by vaccines at senior ages. Moreover, PPARgamma haplo-insufficiency also exists in human known as a rare disease (FPLD3 causing metabolic adverse effects, similar to the mouse. When compared to age- and metabolic disorder-matched other patient samples (FPLD2 not affecting PPARgamma activity, FPLD3 patients showed increased human Trec (hTrec values by qPCR (within healthy human range suggesting delayed thymic senescence, in accordance with

Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma

International Nuclear Information System (INIS)

Leung, Henry W. C.; Liu, Chung-Feng; Chan, Agnes L. F.

2016-01-01

Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO’s guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan

Management of unresectable, locally advanced pancreatic adenocarcinoma.

Science.gov (United States)

Salgado, M; Arévalo, S; Hernando, O; Martínez, A; Yaya, R; Hidalgo, M

2018-02-01

The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

Thymic epithelial cells. I. Expression of strong suppressive (veto) activity in mouse thymic epithelial cell cultures

DEFF Research Database (Denmark)

Claesson, Mogens Helweg; Ropke, C

1990-01-01

We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level. It is conclu......We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level...

Computed tomography of thymic abnormalities

Energy Technology Data Exchange (ETDEWEB)

Schnyder, P.; Candardjis, G.

1987-05-01

Computed tomographic examinations of 38 patients with surgically and histologically proven diagnosis were reviewed. Twenty subjects (52%) had an invasive thymoma and 16% an hyperplastic thymus. Myasthenia gravis was present in 6 cases (16%) of thymic abnormalities, four (10,5%) with invasive thymoma and two (5%) with thymic hyperplasia. Graves' disease was also present in one case of thymic hyperplasia. We emphasize the contribution of CT to the diagnosis and the prognosis.

Computed tomography of thymic abnormalities

International Nuclear Information System (INIS)

Schnyder, P.; Candardjis, G.

1987-01-01

Computed tomographic examinations of 38 patients with surgically and histologically proven diagnosis were reviewed. Twenty subjects (52%) had an invasive thymoma and 16% an hyperplastic thymus. Myasthenia gravis was present in 6 cases (16%) of thymic abnormalities, four (10,5%) with invasive thymoma and two (5%) with thymic hyperplasia. Graves' disease was also present in one case of thymic hyperplasia. We emphasize the contribution of CT to the diagnosis and the prognosis. (orig.)

CT differentiation of invasive thymoma and thymic carcinoma

International Nuclear Information System (INIS)

Lee, Eun Jung; Jung, Gyoo Sik; Kim, Seong Min; Huh, Jin Do; Joh, Young Duk; Shin, Mi Jung; Kim, Jung Sik; Suh, Soo Jhi

1998-01-01

In order to determine the differential points between them, we analyzed the CT findings of invasive thymoma and thymic carcinoma. We retrospectively reviewed the CT scans of 14 patients with invasive thymoma and 15 with thymic carcinoma, confirmed by surgery(n=3D19) or percutaneous needle aspiration(n=3D10) between 1988 and 1996. CT findings were evaluated in each group for intrathoracic spread(posterior, direct posterior, and anterolateral), obliteration of the fat plane between the mass and vascular structures, vessel encasement, invasion of adjacent mediastinal structures, pleural implants, mediastinal nodes and distant metastasis. Direct posterior spread was more common in thymic carcinoma than invasive thymoma;it was seen in one case (7%) of invasive thymoma and 12(80%) of thymic carcinoma(p=3D0.00). Posterior spread was seen in six cases (43%) of in vasive thymoma and nine (60%) of thymic carcinoma. Anterolateral spread was seen only in two cases (13%) of thymic carcinoma. Obliteration of the fat plane was seen in nine cases (64%) of invasive thymoma and 14 (93%) of thymic carcinoma, while vessel encasement was seen in two cases (14%) of invasive thymoma and 13(87%) of thymic carcinoma(p=3D0.00). Invasion of adjacent structures was seen in two cases (14%) of invasive thymoma and eight (53%) of thymic carcinoma. Pleural implants were more common in invasive thymoma than thymic carcinoma, being seen in six cases (43%) of the former and one (7%) of the latter(p=3D0.04). Mediastinal lymphadenopathy was seen in three cases (21%) of invasive thymoma and ten (67%) of thymic carcinoma. Distant metastases were observed only in six cases (40%) of thymic carcinoma(p=3D0.02). Although differentiation between invasive thymoma and thymic carcinoma is difficult on the basis of CT findings, there are certain differential points. Thymic carcinomas showed a higher rate of direct posterior intrathoracic spread, vessel encasement, mediastinal nodes and distant metastases than

[Thymic carcinoma involving aortic arch; report of a case].

Science.gov (United States)

Noriyuki, Toshio; Hamamoto, M; Takazawa, Y; Katoh, K; Hashimoto, M; Kuranishi, F; Nakahara, M; Fukuda, T; Ishizaki, Y; Okuda, H; Akimoto, E; Yonehara, S

2009-05-01

Adenocarcinoma of the thymus is a very rare malignant tumor. The standard treatment for advanced thymic carcinoma has not yet been established, and the prognosis is poor. We report a case of thymic carcinoma that involving the aortic arch and the innominate vein. A 78-year-old woman was admitted to our hospital complaining of hoarseness in April 2007. The computed tomography (CT) scan showed an anterior mediastinal tumor contiguous to the aortic arch and the innominate vein with swelling lymphnodes. Microspcopic examinations of specimens obtained by CT-guided needle biopsy revealed poorly differenciated adenocarcinoma. The carcinoembryonic antigen (CEA) level of serum elevated at 54.9 ng/ml. Thymic carcinoma was diagnosed. The chemoradiotherapy [concurrent, carboplatin (CBDCA) + paclitaxel(TXL)-->vinorelbine (NVB), 60 Gy] was performed, but the effect of the therapy was limited. The resection of the tumor with a part of aortic arch and other peripheral tissues was performed in Augast 2007. The postoperative course was uneventful and the CEA level of serum lowered to the normal. She was discharged 30 days after surgery.

Gallium 67 uptake in thymic rebound

International Nuclear Information System (INIS)

Hurst, R.; Sabio, H.; Teates, C.D.

1988-01-01

We have reported a case of localized thymic enlargement and uptake of gallium 67 in a child who had received antineoplastic chemotherapy. The enlarged thymus showed normal histology, a picture consistent with thymic rebound after nonspecific stress. This case further demonstrates the need to consider thymic rebound as a cause of gallium 67 uptake in children with neoplastic diseases

Multidisciplinary management of the locally advanced unresectable non-small cell lung cancer

International Nuclear Information System (INIS)

Cho, Kwan Ho

2004-01-01

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development of distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas

International Nuclear Information System (INIS)

Medina, Jose Antonio; Rueda, Antonio; Sacchetti de Pasos, Antonio; Contreras, Jorge; Cobo, Manuel; Moreno, Paloma; Benavides, Manuel; Villanueva, Asuncion; Alba, Emilio

2006-01-01

Background and purpose: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. Material and methods: A total of 94 patients (median age, 58 years) with UICC stage III (n=19) and IV (n=75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m 2 weekly, for the first 4 weeks. Results: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. Conclusions: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data

Massive thymic hemorrhage and hemothorax occurring in utero.

Science.gov (United States)

Gargano, Giancarlo; Paltrinieri, Anna Lucia; Gallo, Claudio; Di Pancrazio, Luciana; Roversi, Maria Federica; Ferrari, Fabrizio

2015-11-14

Thymic enlargement is a common and physiological finding in children and neonates' X-rays, but it is usually asymptomatic. Occasionally it can cause respiratory distress. In most cases the aetiology of this expansion remains unclear and it is diagnosed as a thymic hyperplasia. True thymic hyperplasia is defined as a gland expansion, both in size and weight, while maintaining normal microscopic architecture. Often it is a diagnosis of exclusion and prognosis is good. Thymic haemorrhage is an unusual condition related to high foetal and neonatal mortality. We report a case of spontaneous massive thymic haemorrhage in a newborn developing at birth acute respiratory distress associated with severe bilateral haemothorax. Thymic enlargement was evident after pleural evacuation and confirmed by radiographic, Computed Tomography (CT) images and Magnetic Resonance Imaging (MRI) sequences. The spontaneous resolution of this enlargement seen with CT scan and MRI sequences suggested a thymic haemorrhage; surgery was not necessary. Thymic haemorrhage should be considered in newborn infants with pleural effusion, mediastinal space enlargement and Respiratory Distress.

Direct costs associated with the disease management of patients with unresectable advanced non-small-cell lung cancer in The Netherlands.

Science.gov (United States)

Pompen, Marjolein; Gok, Murat; Novák, Annoesjka; van Wuijtswinkel, Rob; Biesma, Bonne; Schramel, Franz; Stigt, Jos; Smit, Hans; Postmus, Pieter

2009-04-01

Disease management and costs of treatment of patients with unresectable advanced non-small-cell lung cancer (NSCLC) in The Netherlands are not well known. A retrospective medical chart review was performed by collecting data from the time of diagnosis until the time of death or the end of the evaluation period. In addition to the demographic data, information was collected on the overall management of the patient. Hospital resource utilisation data collected included number of outpatient specialist visits, number and length of hospitalisation, type and number of diagnostic and laboratory procedures, type and number of radiotherapy cycles and detailed information on chemotherapy. To evaluate the economic impact of second-line treatment, a distinction was made between patients who received only best supportive care (BSC, group A) and those who received chemotherapy as a second-line treatment in addition to BSC (group B). The study was performed from the hospital perspective and reports on 2005 costs. Of 102 patients, 74 belonged to group A and 28 to group B. Patient management included a multidisciplinary approach, the extent of which depended on symptoms of the disease and presence of metastases. The average total treatment cost per patient per year of unresectable advanced NSCLC in The Netherlands was euro32,840 in group A and euro31,187 in group B. In both groups, hospitalisation was the major cost driver. In group B second-line chemotherapy was the second largest contributor of the costs. In spite of the difference in numbers of treatment lines provided to patients in groups A and B the total average costs per patient per year were comparable. Overall, the management of unresectable advanced NSCLC appeared to conform with current guidelines in The Netherlands. These patients show high medical resource consumption, with hospitalisation being the main cost driver in both groups. As economic arguments are becoming increasingly important in medical decision making on

Three dimensional-conformal radiotherapy combined with capecitabine chemotherapy for locally advanced (unresectable) rectal cancer

International Nuclear Information System (INIS)

Zhu Yaqun; Tian Ye; Zhang Junning; Wang Bin

2010-01-01

Objective: To evaluate the compliance and efficacy of chemoradiotherapy for locally advanced (unresectable) rectal cancer. Methods: Thirty eight patients with locally advanced (T4 or recurred) rectal cancer received three dimensional-conformal radiotherapy (for 46 ∼ 50Gy/5 weeks and was boosted to the tumor 16 ∼ 18Gy/2 weeks, 2Gy/fraction, 5 days/week) in combination with capecitabine 1 650mg · m -2 · d -1 , day 1-14, every 3 weeks. Results: The overall response rate was 57.9%, with CR 5 (13.2%), PR 17(44.7%), SD 10 (26.3%), PD 6 (15.8%), median survival time, the 1-year overall survival rate and the 2-year overall survival rate were 18 months, 64.43%, 18.78%, respectively. The remission rate of pain and improvement rate of performance status were 100% and 52.8%. Treatment-related toxicity mainly showed at diarrhea, neutrocytopenia and hand-foot syndrome, the incidence of grade 3 toxicity were 15.8%, 15.8%, 7.9%, respectively. there were no grade 4 toxicity and treatment-related death. Conclusion: Combination of three dimensional-conformal radiotherapy with capecitabine is active in advanced rectal cancer, It is a well-tolerated regimen. (authors)

Review of thymic pathology in 30 cats and 36 dogs.

Science.gov (United States)

Day, M J

1997-09-01

Data are presented from 30 cats and 36 dogs in which thymic disease was recognised clinically or on postmortem examination. The diagnoses included thymic lymphoma (19 cats, 12 dogs), thymoma (five cats, 18 dogs), thymic branchial cyst formation or cystic change (one cat, four dogs), thymic hyperplasia (two cats), congenital hypoplasia (one cat, one dog), thymic haemorrhage (one cat, one dog) and thymic amyloidosis (one cat). Thymic lymphoma occurred in younger dogs and cats, and was recorded equally among domestic shorthaired and purebred (especially Siamese) cats. Eight cats with thymic lymphoma were tested for feline leukaemia virus and four were positive. Thymoma occurred more frequently in older cats and dogs, and in Labradors and German shepherd dogs. Thymic tumours were associated with paraneoplastic hypercalcaemia (six dogs), megaoesophagus (two dogs) or interface dermatitis with basement membrane immune complex deposition (one cat). Non-neoplastic thymic diseases were associated with myasthenia gravis (one cat), pemphigus foliaceus (one cat) and superficial necrolytic dermatitis (one cat).

CT findings of thymic tumors

International Nuclear Information System (INIS)

Chung, Ho Son; Lee, Sang Jin; Hwang, Mi Soo; Cho, Kil Ho; Chang, Jae Chun; Park, Bok Hwan

1991-01-01

A CT scan can make accurate diagnoses of most thymic masses by assessing their size, shape, and internal architecture and is especially effective in detecting pleural implants, mediastinal involvement, and pulmonary parenchymal invasion in malignant thymoma. The authors analyzed the CT findings of 10 histologically-proven thymic masses from 1983 to 1990 in Yeungnam University Hospital. There were 10 cases of thymic masses in the anterior mediastinum consisting of 6 benign, 3 invasive thymomas, and one thymolipoma, while myasthenia gravis was associated with 2 cases of benign thymomas and with one case of invasive thymomas. The CT findings of the benign thymomas (6 cases) were well-defined, bordered, round-or oval-shaped masses with a well-preserved fat plane between the thymic mass and mediastinal great vessels, with no evidence of pleural implants and lung parenchymal invasion. The CT findings of the invasive thymomas (3 cases) were irregular, marginated lobular masses with obliteration of the fat plane between the thymic mass and surrounding great vessels, with evidence of local invasion such as extension to A-P window and mass effect to bronchus. Irregular pleural thickening due to pleural metastasis, multiple metastatic lung parenchymal nodules, and multiple mediastinal lymph node enlargement were also seen in the invasive thymomas. One case of thymolipoma showed an approximately 20cm-size, well-defined fat density mass containing internal septations

CT findings of thymic tumors

Energy Technology Data Exchange (ETDEWEB)

Chung, Ho Son; Lee, Sang Jin; Hwang, Mi Soo; Cho, Kil Ho; Chang, Jae Chun; Park, Bok Hwan [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

1991-05-15

A CT scan can make accurate diagnoses of most thymic masses by assessing their size, shape, and internal architecture and is especially effective in detecting pleural implants, mediastinal involvement, and pulmonary parenchymal invasion in malignant thymoma. The authors analyzed the CT findings of 10 histologically-proven thymic masses from 1983 to 1990 in Yeungnam University Hospital. There were 10 cases of thymic masses in the anterior mediastinum consisting of 6 benign, 3 invasive thymomas, and one thymolipoma, while myasthenia gravis was associated with 2 cases of benign thymomas and with one case of invasive thymomas. The CT findings of the benign thymomas (6 cases) were well-defined, bordered, round-or oval-shaped masses with a well-preserved fat plane between the thymic mass and mediastinal great vessels, with no evidence of pleural implants and lung parenchymal invasion. The CT findings of the invasive thymomas (3 cases) were irregular, marginated lobular masses with obliteration of the fat plane between the thymic mass and surrounding great vessels, with evidence of local invasion such as extension to A-P window and mass effect to bronchus. Irregular pleural thickening due to pleural metastasis, multiple metastatic lung parenchymal nodules, and multiple mediastinal lymph node enlargement were also seen in the invasive thymomas. One case of thymolipoma showed an approximately 20cm-size, well-defined fat density mass containing internal septations.

The International Thymic Malignancy Interest Group thymic initiative: a state-of-the-art study of thymic malignancies.

Science.gov (United States)

Detterbeck, Frank; Korst, Robert

2014-01-01

Thymic malignancies are relatively rare tumors. A general lack of knowledge, misconceptions about benignancy, confusion about the definition of terms, and variability in reporting of outcomes have further hampered progress in these diseases. The International Thymic Malignancy Interest Group has emerged to counter these challenges and has brought together a worldwide multidisciplinary community determined to improve outcomes for these patients. Although the organization is young (initiated in 2010), major early accomplishments have created a foundation and infrastructure for scientific research. These include consensus definitions of terms, an unprecedented global database, development of practical clinical resources and, together with the International Association for the Study of Lung Cancer, development of proposals for the first formal stage classification of these malignant tumors. Many articles have been published or are under way, and a second phase of projects building on the early success is proceeding. The greatest accomplishment of the International Thymic Malignancy Interest Group lies in the establishment of an open culture of collaboration and the engagement of a broad group of individuals united by a common mission. It is a testament to what can be achieved, despite ongoing and inherent challenges, by determination and a collective effort. Copyright © 2014 Elsevier Inc. All rights reserved.

Computed tomography of thymic abnormalities: review of 10 patients

International Nuclear Information System (INIS)

Marins, J.L.C.; Brito Pacheco, E.M. de; Cazerta, N.M.G.; Silva, M.J.G. da

1990-01-01

Chest radiographs and computed tomographic scans of the mediastinum were correlated with pathologic findings of the thymus following thymectomy in 10 patients with thymic disease. There were five patients with thymoma, four with thymic hiperplasia and one with benign thymic cyst. Computed tomography shoud be the imaging method of choice following plain chest radiographs when a suspect thymic abnormality requires further evaluation. Recognition of variations in the normal location, size, shape and density of the thymus prevents misinterpretation as abnormal mediastinal mass. Furthermore, knowledge of the normal computed tomography appearance has proved helpful in evaluating thymic abnormalities. (author)

The effect of age on thymic function

Directory of Open Access Journals (Sweden)

Donald B. Palmer

2013-10-01

Full Text Available Age-related regression of the thymus is associated with a decline in naïve T cell output. This is thought to contribute to the reduction in T cell diversity seen in older individuals and linked with increased susceptibility to infection, autoimmune disease and cancer. Thymic involution is one of the most dramatic and ubiquitous changes seen in the ageing immune system, but the mechanisms which underlying this process are poorly understood. However, a picture is emerging, implicating the involvement of both extrinsic and intrinsic factors. In this review we assess the role of the thymic microenvironment as a potential target that regulates thymic involution, question whether thymocyte development in the aged thymus is functionally impaired and explore the kinetics of thymic involution.

nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma

Directory of Open Access Journals (Sweden)

Go Makimoto

2014-01-01

Full Text Available We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

Adjuvant Therapy for Thymic Carcinoma--A Decade of Experience in a Taiwan National Teaching Hospital.

Directory of Open Access Journals (Sweden)

Yen-Han Tseng

Full Text Available Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma.To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014.Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS and overall survival (OS were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003. Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11. Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029. Among 30 patients (with stage I- IV carcinoma who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months than 2 patients who received adjuvant chemotherapy (5.9 months or 4 patients who received concurrent chemoradiotherapy (7.5 months after surgery (p = 0.003.Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection.

Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

Science.gov (United States)

Kong, Ling-Yan; Zhang, Wei; Zhou, Yue; Xu, Hai; Shi, Hai-Bin; Feng, Qing; Xu, Xiao-Quan; Yu, Tong-Fu

2018-04-01

To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADC HS-ROI ) and histogram-based approach. ADC histogram parameters included mean ADC (ADC mean ), median ADC (ADC median ), 10 and 90 percentile of ADC (ADC 10 and ADC 90 ), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADC mean , ADC median , ADC 10 , ADC 90 and ADC HS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could help to evaluate Masaoka clinical stages of thymic epithelial tumours. 3. ADC 10 might be a promising imaging biomarker for assessing and characterizing thymic epithelial tumours.

Clinical experience with intravenous radiosensitizers in unresectable sarcomas

International Nuclear Information System (INIS)

Kinsella, T.J.; Glatstein, E.

1987-01-01

Traditionally, adult bone and soft tissue sarcomas have been considered to be ''radioresistant.'' Because of this philosophy, patients who present with locally advanced, unresectable sarcomas often are treated in a palliative fashion, usually with low-dose radiotherapy. Over the last 6 years, 29 patients with unresectable primary or metastatic sarcomas were treated using a combination of intravenous chemical radiosensitizers and high-dose irradiation. Twenty-two of 29 patients achieved clinical local control, with six patients having a complete clinical response. The time to tumor response is often several months or longer, which is in contrast to other tumor histologies (carcinomas, lymphomas), where tumor response usually occurs over several weeks. Several large tumors have shown only a minimal tumor response, yet were found to be sterilized in posttreatment biopsy or autopsy examination. Of 15 patients with primary sarcomas without metastases, 11 patients (73%) remain free of local tumor progression from 12 to 83 months. Adult high-grade sarcomas can be controlled with high-dose radiotherapy and intravenous radiosensitizers, although the precise role of these agents is unclear

Palliative radiotherapy in asymptomatic patients with locally advanced, unresectable, non-small cell lung cancer

International Nuclear Information System (INIS)

Reinfuss, M.; Skolyszewski, J.; Kowalska, T.; Rzepecki, W.; Kociolek, D.

1993-01-01

Between 1983 and 1990, 332 patients with non-small cell lung cancer (NSCLC) were referred to short-time, split-course palliative thoracic radiotherapy. The group consisted of patients with locally advanced (III o ), unresectable cancer, not suitable for curative radiotherapy, asymptomatic or having only minimal symptoms related to intrathoracic tumor. The therapeutic plan involved two series of irradiation. Tumor dose delivered in each series was 20 Gy given in five daily fractions over five treatment days. There were four weeks interval between series. Of 332 patients initially qualified to thoracic radiotherapy only 170 patients received the treatment; the other 162 patients were not irradiated because of treatment refusal or logistic problems concerning therapy. They made the control group of the study, receiving the best possible symptomatic care. Twelve-month survivals in the radiotherapy and control groups were 32.4% and 9.3%, respectively; 24-month survivals 11.2% and 0%, respectively. Improvement of survival after palliative thoracic radiotherapy was observed only in patients with clinical stage IIIA and Karnofsky's performance status (KPS) ≥ 70. (orig.) [de

Rag defects and thymic stroma: lessons from animal models

Directory of Open Access Journals (Sweden)

Veronica eMarrella

2014-06-01

Full Text Available Thymocytes and thymic epithelial cells (TECs cross-talk is essential to support T-cell development and preserve thymic architecture and maturation of TECs and Foxp3+ natural regulatory T (nTreg cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development (leading to Severe Combined Immune Deficiency, SCID or late stages in thymocyte maturation (resulting in combined immunodeficiency. Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS. In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells (DCs and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signalling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution.

Thymic hyperplasia in Graves′ disease

Directory of Open Access Journals (Sweden)

Narendra Kotwal

2013-01-01

Full Text Available Graves′ disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. It is known to be associated with autoimmune conditions such as myasthenia gravis, Addison′s disease, type 1 diabetes mellitus, and vitiligo. We present a case of rare autoimmune association of Graves′ disease with thymic hyperplasia which regressed after treatment with antithyroid drugs. Exact pathophysiology of thymic hyperplasia in Graves′ is not well understood; it is likely to be the result of rather than the cause of Graves′ disease.

Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

Science.gov (United States)

Lopes, Noella; Vachon, Hortense; Marie, Julien; Irla, Magali

2017-06-01

Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 + thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Thymic epithelial tumors: Comparison of CT and MR imaging findings of low-risk thymomas, high-risk thymomas, and thymic carcinomas

International Nuclear Information System (INIS)

Sadohara, Junko; Fujimoto, Kiminori; Mueller, Nestor L.; Kato, Seiya; Takamori, Shinzo; Ohkuma, Kazuaki; Terasaki, Hiroshi; Hayabuchi, Naofumi

2006-01-01

Objective: To assess the CT and magnetic resonance (MR) imaging findings of thymic epithelial tumors classified according to the current World Health Organization (WHO) histologic classification and to determine useful findings in differentiating the main subtypes. Materials and methods: Sixty patients with thymic epithelial tumor who underwent both CT and MR imaging were reviewed retrospectively. All cases were classified according to the 2004 WHO classification. The following findings were assessed in each case on both CT and MRI: size of tumor, contour, perimeter of capsule; homogeneity, presence of septum, hemorrhage, necrotic or cystic component within tumor; presence of mediastinal lymphadenopathy, pleural effusion, and great vessel invasion. These imaging characteristics of 30 low-risk thymomas (4 type A, 12 type AB, and 14 type B1), 18 high-risk thymomas (11 type B2 and seven type B3), and 12 thymic carcinomas on CT and MR imaging were compared using the chi-square test. Comparison between CT and MR findings was performed by using McNemar test. Results: On both CT and MR imaging, thymic carcinomas were more likely to have irregular contours (P < .001), necrotic or cystic component (P < .05), heterogeneous contrast-enhancement (P < .05), lymphadenopathy (P < .0001), and great vessel invasion (P < .001) than low-risk and high-risk thymomas. On MR imaging, the findings of almost complete capsule, septum, and homogenous enhancement were more commonly seen in low-risk thymomas than high-risk thymomas and thymic carcinomas (P < .05). MR imaging was superior to CT in the depiction of capsule, septum, or hemorrhage within tumor (all comparison, P < .05). Conclusion: The presence of irregular contour, necrotic or cystic component, heterogeneous enhancement, lymphadenopathy, and great vessel invasion on CT or MR imaging are strongly suggestive of thymic carcinomas. On MR imaging, the findings of contour, capsule, septum, and homogenous enhancement are helpful in

Mutational status of EGFR and KIT in thymoma and thymic carcinoma.

Science.gov (United States)

Yoh, Kiyotaka; Nishiwaki, Yutaka; Ishii, Genichiro; Goto, Koichi; Kubota, Kaoru; Ohmatsu, Hironobu; Niho, Seiji; Nagai, Kanji; Saijo, Nagahiro

2008-12-01

This study was conducted to evaluate the prevalence of EGFR and KIT mutations in thymomas and thymic carcinomas as a means of exploring the potential for molecularly targeted therapy with tyrosine kinase inhibitors. Genomic DNA was isolated from 41 paraffin-embedded tumor samples obtained from 24 thymomas and 17 thymic carcinomas. EGFR exons 18, 19, and 21, and KIT exons 9, 11, 13, and 17, were analyzed for mutations by PCR and direct sequencing. Protein expression of EGFR and KIT was evaluated immunohistochemically. EGFR mutations were detected in 2 of 20 thymomas, but not in any of the thymic carcinomas. All of the EGFR mutations detected were missense mutations (L858R and G863D) in exon 21. EGFR protein was expressed in 71% of the thymomas and 53% of the thymic carcinomas. The mutational analysis of KIT revealed only a missense mutation (L576P) in exon 11 of one thymic carcinoma. KIT protein was expressed in 88% of the thymic carcinomas and 0% of the thymomas. The results of this study indicate that EGFR and KIT mutations in thymomas and thymic carcinomas are rare, but that many of the tumors express EGFR or KIT protein.

Perioperative high dose rate (HDR brachytherapy in unresectable locally advanced pancreatic tumors

Directory of Open Access Journals (Sweden)

Brygida Białas

2011-07-01

Full Text Available Purpose: The aim of the study was to present an original technique of catheter implantation for perioperative HDR-Ir192 brachytherapy in patients after palliative operations of unresectable locally advanced pancreatic tumors and to estimate the influence of perioperative HDR-Ir192 brachytherapy on pain relief in terminal pancreatic cancer patients. Material and methods: Eight patients with pancreatic tumors located in the head of pancreas underwent palliative operations with the use of HDR-Ir192 brachytherapy. All patients qualified for surgery reported pain of high intensity and had received narcotic painkillers prior to operation. During the last phase of the surgery, the Nucletron® catheters were implanted in patients to prepare them for later perioperative brachytherapy. Since the 6th day after surgery HDR brachytherapy was performed. Before each brachytherapy fraction the location of implants were checked using fluoroscopy. A fractional dose was 5 Gy and a total dose was 20 Gy in the area of radiation. A comparative study of two groups of patients (with and without brachytherapy with stage III pancreatic cancer according to the TNM scale was taken in consideration. Results and Conclusions: The authors claim that the modification of catheter implantation using specially designed cannula, facilitates the process of inserting the catheter into the tumor, shortens the time needed for the procedure, and reduces the risk of complications. Mean survival time was 5.7 months. In the group of performed brachytherapy, the mean survival time was 6.7 months, while in the group of no brachytherapy performed – 4.4 months. In the group of brachytherapy, only one patient increased the dose of painkillers in the last month of his life. Remaining patients took constant doses of medicines. Perioperative HDR-Ir192 brachytherapy could be considered as a practical application of adjuvant therapy for pain relief in patients with an advanced pancreatic cancer.

Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma

DEFF Research Database (Denmark)

Oliveri, Roberto S; Wetterslev, Jørn; Gluud, Christian

2011-01-01

Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC.......Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC....

Thymic enlargement in patients with hyperthyroidism

Energy Technology Data Exchange (ETDEWEB)

Myung, Jae Sung; Goo, Jin Mo; Im, Jung Gi [College of medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of); Kim, Mi Young [Sejong General Hospital, Seoul (Korea, Republic of); Park, Yang Hee [National Police Hospital, Seoul (Korea, Republic of)

2000-08-01

To evaluate the radiologic findings and clinical feasibility of thymic enlargement in patients with hyperthyroidism. Seven patients with hyperthyroidism and anterior mediastinal bulging revealed by chest radiography were evaluated. The CT findings were analyzed with regard to the shape of the anterior mediastinal mass, surrounding infiltration, and enlargement of mediastinal lymph nodes. Whether or not tumor markers (alpha-fetoprotein, beta-human chorionic gonadotrophin, and chorionic embryonic antigen) showed increased levels was determined, and the size and thickness of the anterior mediastinal mass were measured and compared with previously described age-matched thymus data. In addition, changes in the thyroid gland were evaluated. In all seven patients, anterior mediastinal masses were bi-lobed, with no surrounding infiltration or enlarged mediastinal lymph node, and tumor marker levels showed no increase. The masses were therefore considered to be thymus. In six patients, the size of the thymus exceeded two upper standard deviations of mean value and in one patient, it was smaller than this. In three patients, PCNB (percutaneous needle biopsy) revealed normal thymic tissue and in two, follow-up chest PA demonstrated no interval change. CT showed that in three patients, the thyroid glands were diffusely enlarged. In patients with hyperthyroidism, an anterior mediastinal mass seen on chest radiographs was due to thymic enlargement. The recognition of CT findings of thymic enlargement in such patients may avoid unnecessary biopsy. (author)

Effects of neonatal thymic exposure to high doses of X-irradiation

International Nuclear Information System (INIS)

Bains, G.S.; Sundaram, K.

1979-01-01

The thymic region of neonatal Swiss mice was exposed to doses varying from 1000 R to 2000 R of X-irradiation. The animals did not show any signs of wasting syndrome up to 6 months after irradiation. At this time hyperplasia of the thymus with an associated lymphocytosis was evident in irradiated animals. Antibody production to sheep red blood cells (SRBC) was not affected. However, at 12 months post-irradiation the animals showed signs of wasting disease with a progressive increase in their numbers at 18 and 24 months of age. The percentage incidence of animals with wasting disease was dose dependent. At this stage in the majority of the animals with the disease the thymus showed varying degrees of atrophy along with splenomegaly. There were no significant differences in the number of lymphocytes but the number of granulocytes showed a substantial increase. This was more evident in animals exposed to 2000 R to the thymic region. Though one observed a lowered ability to form antibodies to bovine serum albumin (BSA) with advancing age, the thymic irradiation did not affect the immune response to BSA even in animals manifesting wasting disease. An interesting observation has been the development of a severe loss of muscle power and tone in the hind limbs in a large majority of animals. (author)

Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma

DEFF Research Database (Denmark)

Geoerger, Birgit; Bergeron, Christophe; Gore, Lia

2017-01-01

BACKGROUND: Ipilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available. METHODS: Patients aged 12 to <18 years with previously treated or untreated, unresectable stage III or IV mal...

Heat shock protein 90-sheltered overexpression of insulin-like growth factor 1 receptor contributes to malignancy of thymic epithelial tumors.

Science.gov (United States)

Breinig, Marco; Mayer, Philipp; Harjung, Andreas; Goeppert, Benjamin; Malz, Mona; Penzel, Roland; Neumann, Olaf; Hartmann, Arndt; Dienemann, Hendrik; Giaccone, Giuseppe; Schirmacher, Peter; Kern, Michael André; Chiosis, Gabriela; Rieker, Ralf Joachim

2011-04-15

The underlying molecular mechanisms of thymic epithelial malignancies (TEMs) are poorly understood. Consequently, there is a lack of efficacious targeted therapies and patient prognosis remains dismal, particularly for advanced TEMs. We sought to investigate protumorigenic mechanism relevant to this understudied cancer. Recently established cell lines derived from thymic epithelial tumors were used as a model system. The antitumor activity of specific heat shock protein 90 (Hsp90) inhibitors was investigated by an analysis of cell viability, cell cycle, and apoptosis using MTT-assays and flow cytometry. Western blotting was used to investigate the altered expression of Hsp90 clients. Pharmacological inhibitors against select Hsp90 clients, as well as RNAi, were employed to test the relevance of each client independently. Tissue microarray analysis was performed to match the in vitro findings with observations obtained from patient-derived samples. Hsp90 inhibition significantly reduces cell viability of thymic carcinoma cells, induces cell cycle arrest and apoptosis, and blocks invasiveness. Hsp90 inhibition triggers the degradation of multiple oncogenic clients, for example insulin-like growth factor 1 receptor (IGF-1R), CDK4, and the inactivation of PI3K/Akt and RAF/Erk signaling. Mechanistically, the IGF/IGF-1R-signaling axis contributes to the establishment of the antiapoptotic phenotype of thymic cancer cells. Finally, IGF-1R is overexpressed in advanced TEMs. We have unraveled a novel protumorigenic mechanism in TEMs, namely Hsp90-capacitated overexpression of IGF-1R, which confers apoptosis evasion in malignant thymic epithelial cells. Our data indicate that Hsp90 inhibition, which simultaneously blocks multiple cancer hallmarks, represents a therapeutic strategy in TEMs that may merit evaluation in clinical trials. ©2011 AACR.

Thymic pathology and cardiac myxomas: Coincidence or a closer relationship?

Science.gov (United States)

Moraitis, Sotirios D; Agrafiotis, Apostolos C; Pappas, Dimitrios; Pothitakis, Chrysovalantis; Stergianni, Maria; Koukis, Ioannis

2018-04-30

Myxomas are the most common benign cardiac tumors and are located more frequently in the left atrium. In the literature there are cases describing the coexistence of thymic tumors and cardiac myxomas. In the case reported herein, during the resection of a cardiac myxoma, an enlarged thymus gland was encountered and resected. The histological exam revealed a thymic hyperplasia. The aim of this case study is to assess the need of conducting further studies in order to identify a common histological pathway between thymic lesions and cardiac myxomas. The diagnosis of a cardiac myxoma could justify a further workup of the anterior mediastinum in order not to overlook a lesion of thymic origin.

Immune activation is associated with decreased thymic function in ...

African Journals Online (AJOL)

Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIVpositive treatment-naive individuals has thus far not been ...

Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

Energy Technology Data Exchange (ETDEWEB)

Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A. [Univ. Graz (Austria). Dept. of Radiotherapy; Beham-Schmid, C. [Univ. Graz (Austria). Dept. of Pathology; Groell, R. [Univ. Graz (Austria). Dept. of Radiology; Smolle-Juettner, F.M.; Renner, H. [Univ. Graz (Austria). Dept. of Thoracic and Hyperbaric Surgery; Quehenberger, F. [Univ. Graz (Austria). Dept. of Medical Informatics, Statistics and Documentation

1999-06-01

All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [Deutsch] Alle 33 Patienten wurden nach kompletter Resektion (n=16), Teilresektion (n=9) oder Biopsie (n=8) mit einer mittleren Dosis von 50 Gy (30 bis 60 Gy) bestrahlt. Die Stadieneinteilung nach Masaoka ergab jeweils zwoelf Patienten in Stadium II und III sowie neun Patienten im Stadium IV. Ergebnisse: Patienten mit einem invasivem Thymom Masaoka-Stadium II bis IV (mediane Nachsorgezeit 54,4 Monate) hatten ein Fuenf-Jahres-Gesamtueberleben, krankheitsspezifisches und

Thymic B cell development is controlled by the B potential of progenitors via both hematopoietic-intrinsic and thymic microenvironment-intrinsic regulatory mechanisms.

Directory of Open Access Journals (Sweden)

Shiyun Xiao

Full Text Available Hematopoietic stem cells (HSCs derived from birth through adult possess differing differentiation potential for T or B cell fate in the thymus; neonatal bone marrow (BM cells also have a higher potential for B cell production in BM compared to adult HSCs. We hypothesized that this hematopoietic-intrinsic B potential might also regulate B cell development in the thymus during ontogeny.Foxn1lacZ mutant mice are a model in which down regulation of a thymic epithelial cell (TEC specific transcription factor beginning one week postnatal causes a dramatic reduction of thymocytes production. In this study, we found that while T cells were decreased, the frequency of thymic B cells was greatly increased in these mutants in the perinatal period. We used this model to characterize the mechanisms in the thymus controlling B cell development.Foxn1lacZ mutants, T cell committed intrathymic progenitors (DN1a,b were progressively reduced beginning one week after birth, while thymic B cells peaked at 3-4 weeks with pre-B-II progenitor phenotype, and originated in the thymus. Heterochronic chimeras showed that the capacity for thymic B cell production was due to a combination of higher B potential of neonatal HSCs, combined with a thymic microenvironment deficiency including reduction of DL4 and increase of IL-7 that promoted B cell fate.Our findings indicate that the capacity and time course for thymic B-cell production are primarily controlled by the hematopoietic-intrinsic potential for B cells themselves during ontogeny, but that signals from TECs microenvironment also influence the frequency and differentiation potential of B cell development in the thymus.

CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis

International Nuclear Information System (INIS)

Liu Fugeng; Wei Jiahu; Pan Jishu; Zhou Cheng; Chen Qihang; Yu Jingying; Wu Guogeng; Xu Xianhao

2006-01-01

Objective: To evaluate the CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis (MG). Methods: The CT findings of thymus area of 134 adult patients with lymphofollicular thymic hyperplasia in MG were reviewed, all of them with surgically and histologically proven diagnosis, and compared with the CT findings of 165 normal subjects. Results: In the group of patient, CT showed enlargement of thymus in 31 patients, 5 patients had nodule or mass ( 3 cm) and 9 patients (6.7%) had normal size thymus with soft-tissue density, it can considered with thymic hyperplasia. The spotty or streak shadow showed in other patients, though it could not be certain diagnosed as thymic hyperplasia, but could not be except it. The thymus area tissue complete replacement by fatty density were not found in patient group. The CT findings of patients had marked difference when compared with group of normal subjects (P<0.01), except the spotty or streak shadows. Conclusion: CT scan is an important method in diagnosing thymic lymphofollicular hyperplasia of MG in adult. (authors)

Radiofrequency ablation for unresectable locally advanced pancreatic cancer: a systematic review

Science.gov (United States)

Fegrachi, Samira; Besselink, Marc G; van Santvoort, Hjalmar C; van Hillegersberg, Richard; Molenaar, Izaak Quintus

2014-01-01

Background: Median survival in patients with unresectable locally advanced pancreatic cancer lies in the range of 9–15 months. Radiofrequency ablation (RFA) may prolong survival, but data on its safety and efficacy are scarce. Methods: A systematic literature search was performed in PubMed, EMBASE and the Cochrane Library with the syntax ‘(radiofrequency OR RFA) AND (pancreas OR pancreatic)’ for studies published until 1 January 2012. In addition, a search of the proceedings of conferences on pancreatic disease that took place during 2009–2011 was performed. Studies with fewer than five patients were excluded as they were considered to be case reports. The primary endpoint was survival. Secondary endpoints included morbidity and mortality. Results: Five studies involving a total of 158 patients with pancreatic cancer treated with RFA fulfilled the eligibility criteria. These studies reported median survival after RFA of 3–33 months, morbidity related to RFA of 4–37%, mortality of 0–19% and overall morbidity of 10–43%. Pooling of data was not appropriate as the study populations and reported outcomes were heterogeneous. Crucial safety aspects included ensuring a maximum RFA tip temperature of < 90 °C and ensuring minimum distances between the RFA probe and surrounding structures. Conclusions: Radiofrequency ablation seems to be feasible and safe when it is used with the correct temperature and at an appropriate distance from vital structures. It appears to have a positive impact on survival. Multicentre randomized trials are necessary to determine the true effect size of RFA and to minimize the impacts of selection and publication biases. PMID:23600801

Evaluation of thymic tumors with 18F-FDG PET-CT - A pictorial review

International Nuclear Information System (INIS)

Sharma, Punit; Singhal, Abhinav; Bal, Chandrasekhar; Malhotra, Arun; Kumar, Rakesh; Kumar, Arvind

2013-01-01

Thymic tumors represent a broad spectrum of neoplastic disorders and pose considerable diagnostic difficulties. A non-invasive imaging study to determine the nature of thymic lesions can have significant impact on management of such tumors. 18F-flurorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has shown promising results in characterization of thymic tumors. The objective of this article is to provide an illustrative tutorial highlighting the clinical utility of 18F-FDG PET-CT imaging in patients with thymic tumors. We have pictorially depicted the 18F-FDG PET-CT salient imaging characteristics of various thymic tumors, both epithelial and non-epithelial. Also discussed is the dynamic physiology of thymus gland which is to be kept in mind when evaluating thymic pathology on 18F-FDG PET-CT, as it can lead to interpretative pitfalls

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study

NARCIS (Netherlands)

Psyrri, A.; Fortpied, C.; Koutsodontis, G.; Avgeris, M.; Kroupis, C.; Goutas, N.; Menis, J.; Herman, L.; Giurgea, L.; Remenar, E.; Degardin, M.; Pateras, I.S.; Langendijk, J.A.; Herpen, C.M.L. van; Awada, A.; Germa-Lluch, J.R.; Kienzer, H.R.; Licitra, L.; Vermorken, J.B.

2017-01-01

Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel : a subset analysis of EORTC 24971 study

NARCIS (Netherlands)

Psyrri, A; Fortpied, C; Koutsodontis, G; Avgeris, M; Kroupis, C; Goutas, N; Menis, J; Herman, L; Giurgea, L; Remenar, E; Degardin, M; Pateras, I S; Langendijk, J A; van Herpen, C; Awada, A; Germà-Lluch, J R; Kienzer, H R; Licitra, L; Vermorken, J B

Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF over PF, in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable HNSCC. We conducted a retrospective analysis of prospectively collected data aiming to

Ectopic Thymic Cyst of the Subglottis: Considerations for Diagnosis and Management.

Science.gov (United States)

Ahmad, Iram; Kirby, Patricia; Liming, Bryan

2018-03-01

To share the diagnostic and management challenges created by an extremely rare airway lesion-the subglottic ectopic thymic cyst. Case report and literature review. We review the presentation, management, and clinical course of an infant who presented with a subglottic mass that was histologically confirmed as a thymic cyst. A brief literature review supplements the case presentation Results: We present the third described case of an ectopic thymic cyst presenting as a subglottic mass. The differential diagnosis of subglottic masses in neonates consists primarily of subglottic hemangioma and mucous retention cysts. Otolaryngologists must be prepared for unexpected findings when dealing with critical airways. We compare the presentation and management of our patient with the 2 previously described cases. We propose an embryologic theory for the origin of these rare lesions. An ectopic thymic cyst is a rare and unexpected cause of neonatal stridor. Management of pediatric airway lesions must allow for unexpected findings at the time of diagnostic and therapeutic endoscopy. The appropriate management of subglottic thymic cysts is poorly defined, but close surveillance for recurrence is mandatory.

Radiation-induced quantitative alterations in prenatal thymic development in the beagle dog

International Nuclear Information System (INIS)

Miller, G.K.; Benjamin, S.A.

1985-01-01

Quantitative morphology of the canine fetal thymus was studied to evaluate the age-dependent radiosensitivity of the developing immune system. Pregnant beagle dams received abdominal 60 Co gamma exposures (200 R) or were sham irradiated at one of three ages in gestation, 30, 40, or 45 days. The mean calculated dose to each fetus was 1.5 Gray. One-half of the fetuses in each litter were harvested by hysterotomy at 5 days and one-half at 10 days post-irradiation (PI). The volumes of the thymic lobules and lobular cortices were significantly reduced at 5 and 10 days PI when compared with age-matched controls. Thymic cortical volumes in irradiated fetuses were reduced between 13 and 29% from control volumes by 5 days PI and 8 and 13% by 10 day PI. Thymic medullary volumes in irradiated fetuses were reduced 18 to 23% by 5 days PI and 27 to 54% by 10 days PI. The reductions in medullary volumes in fetuses irradiated at 35, 40, and 45 days of gestation and evaluated at 10 days PI were 54, 38, and 27%, respectively. Although injury to both thymic cortices and medullas was greater following exposures earlier in gestation, damage to medullas was relatively more severe than in cortices following exposure at any one age. The degree of reduction of medullary volume reflects thymic epithelial injury and is surprising since thymic epithelium is considered to be radioresistant in the adult. Such injury may have serious consequences postnatally as normal differentiation of T cell subpopulations is dependent upon the integrity of the thymic microenvironment. Damage to the thymic microenvironment could result in defects in immunologic regulation and in immune deficiencies

Sonographic measurement of thymic size in healthy Korean neonates

International Nuclear Information System (INIS)

Seo, Hyun Joo; Yoon, Dae Young; Han, Dae Hee; Han, Sang Wook; Kim, Ho Chul; Kim, Young Mook; Choi, Chul Soon; Bae, Sang Hoon

2001-01-01

To assess the variation in thymic size in healthy Korean neonates by sonography and to study the possible correlation to clinical variables. This study was made of 112 healthy Korean neonates (94 full-term and 18 preterm), at less than a week of age. The transverse diameter of the thymus was measured in a transverse scan and the largest sagittal area was assessed in a longitudinal scan. The thymic index was defined as the product of these two values. Then, this index was compared to clinical variables, such as sex, delivery method (spontaneous delivery vs cesarian section), body weight, height, body surface area, head circumference, chest circumference, gestational age, and maternal age in both full-term and preterm groups. The thymic index was 9.6 ± 3.1 (range 3.1-20.2) in full-term and 4.2 ± 2.4 (range 0.9-9.9) in preterm neonates, respectively. The thymic index was positively correlated to the body weight (R=0.550 in full-term, R=0.669 in preterm) and body surface area (R=0.540 in full-term, R=0.674 in preterm) in both full-term and preterm groups (p<0.01). There was no statistically significant correlation to sex, delivery method, height, head circumference, chest circumference, maternal age or gestational age. The thymic index in Healthy Korean neonates as measured by sonography is significantly correlated to the body weight and body surface area of the neonate.

Thymic epithelial tumours: from basic principles to individualised treatment strategies

Directory of Open Access Journals (Sweden)

Nicolas Girard

2013-03-01

Full Text Available Thymic epithelial tumours represent a wide range of anatomical, clinical, histological and molecular malignant entities that may be aggressive and difficult to treat. The histopathological classification distinguishes thymomas from thymic carcinomas. Thymomas may be associated with autoimmune disorders. The management of thymic epithelial tumours is a paradigm of co-operation between clinicians, surgeons and pathologists, from establishing the diagnosis to organising the multimodal therapeutic strategy. Surgery is the mainstay of the curative-intent treatment, as complete resection represents the most significantly favourable prognostic factor on overall survival. In case of invasion of intra-thoracic structures and/or dissemination to the pleura and the pericardium, precluding complete resection to be achieved, primary chemotherapy has been used to reduce the tumour burden, possibly allowing subsequent surgery and/or radiotherapy. Novel strategies are needed, especially for refractory, recurrent tumours and thymic carcinomas, which carry a poor prognosis. Personalised approaches are currently being developed, as potentially “druggable” molecular targets are emerging from recent integrated genomic analyses. Along with the large variety of questions relative to the treatment strategy, thymic epithelial tumours represent a model of therapeutic implementation and achievement in orphan thoracic oncology, showing how the advent of new results induces new questions, as well as diversifies further clinical research directions and international collaborative initiatives.

Thymic nurse cells and thymic repopulation after whole body sublethal irradiation in mice

International Nuclear Information System (INIS)

Houben-Defresne, M.P.; Varlet, A.; Boniver, J.

1984-01-01

Thymic Nurse Cells (TNCs) are lymphoepithelial complexes which are thought to play a role in the early stages of the intrathymic differentiation pathway. Their repopulation kinetics were analyzed in mice after sublethal whole-body irradiation. Changes of the number of TNCs per thymus were parallel with the evolution of the whole thymocyte population. Particularly, a first wave of TNCs restoration was followed by a secondary depletion and a final recovery. This suggests that TNCs restoration is related to the proliferating progeny of intrathymic radioresistant thymocytes. When normal bone marrow cells were grafted intravenously after irradiation, no secondary depletion was found. This pattern of restoration was obviously related to thymic repopulation by cells which were derived from the inoculated bone marrow. Homing studies with FITC labelled bone marrow cells showed that inoculated bone marrow cells did not penetrate TNCs early after irradiation. Later on, when immigrant cells started to proliferate, they were found preferentially within TNCs before spreading in the whole thymus. (Auth.)

LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells

Directory of Open Access Journals (Sweden)

Keitaro Hayashi

2016-11-01

Full Text Available L-type amino acid transporter 1 (LAT1, SLC7A5 incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

Effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice

International Nuclear Information System (INIS)

Huston, D.P.; Smathers, P.A.; Reeves, J.P.; Steinberg, A.D.

1983-01-01

The effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice were studied. Neonatally thymectomized male and female F1 mice reconstituted with a parental or F1-irradiated thymic lobe were compared to nonreconstituted and sham-thymectomized controls. While maleness retarded the spontaneous production of ss- and ds-DNA antibodies, thymic grafts did not suppress antibodies to ss-DNA in either sex, but did suppress the production of antibodies to ds-DNA in female mice. A unique property of NZB thymic grafts was the inability to suppress anti-RBC antibodies in male mice. Thus, (i) the gender of the F1 recipient was the most important determinant of production of antibodies to ss-DNA, (ii) either maleness or the thymic microenvironment could retard production of anti-ds-DNA antibodies, and (iii) both gender and the thymic microenvironment were important in the regulation of anti-RBC antibody production. Since the administration of thymosin did not suppress autoantibody production, the effects of the thymic grafts was not solely via thymic hormone production. These studies suggest that sex hormones and/or the thymic microenvironment can exert a suppressive effect on autoantibody production and that autoantibodies differ in their susceptibility to such suppression

Intrapericardial primary thymic carcinoma in a 73-year-old man.

Science.gov (United States)

Calderon, Ana Maria; Merchan, Juan Andres; Rozo, Juan Carlos; Guerrero, Cesar Ivan; Treistman, Bernardo; Sulak, Laura E; Cheong, Benjamin Y C; Rodríguez, German; Mesa, Andrés

2008-01-01

Thymic carcinoma is a rare, highly aggressive type of tumor that typically occurs in the anterior mediastinum. We describe the case of a 73-year-old man who presented with weakness, cough, dyspnea, anorexia, and weight loss. An echocardiogram showed an intrapericardial mass that occupied the space around the lateral walls of the left ventricle and distally compressed the right ventricle. Magnetic resonance imaging and a biopsy confirmed the presence of intrapericardial primary thymic carcinoma. The patient underwent surgical excision of the tumor and died of right ventricular rupture during the procedure. This case highlights the importance of considering thymic carcinoma whenever an otherwise unexplained intrapericardial mass is encountered.

Isolated splenic metastasis from a thymic carcinoma: A case report.

Science.gov (United States)

Chen, Dongmei; Meng, Xiangying; Zhao, Yaowei; Wu, Shikai

2016-09-01

Thymic carcinomas are rare tumors that arise in the anterior mediastinum. Most of these malignancies develop local metastases limited in the thorax. Splenic metastases from thymic carcinomas are extremely rare. Here we report a case of isolated splenic metastasis from a 38-year-old female patient with Stage IV thymic carcinoma, who was treated with chemoradiotherapy. At twenty-2 months follow-up, the patient was found to have an isolated spleen metastasis, which was treated by Cyberknife with a reduced size of the metastasis, representing a partial response. Although splenic metastasis is a rare phenomenon, physicians need to be aware of the possibility of such metastases.

Fate of thymic radioactivity after local labeling with 125Iododeoxyuridine

International Nuclear Information System (INIS)

Laissue, J.A.; Chanana, A.D.; Cottier, H.; Cronkite, E.P.; Joel, D.D.

1976-01-01

The thymic cortex was locally labeled with 125 Iododeoxyuridine ( 125 IUdR) in young adult mice in an attempt to provide a simple quantitative assessment of the fate of cortical thymocytes. Similarly operated and nonoperated mice given 125 IUdR intravenously were used for comparison. Analogous experiments were performed in adrenalectomized animals. More than 90 percent of thymic activity present 1 day after labeling had been lost by day 8. That proportion of radioactivity contributed to a given organ by accumulation of labeled thymic migrants was estimated by comparison of values obtained after local labeling with those acquired after systemic labeling. Thymic cell accumulation was apparent in the intestine, spleen, mesenteric lymph node, and femurs of locally labeled mice; however, only a few percent of the total activity lost from the thymus was accounted for in these lymphoid organs. The pattern of fecal and urinary elimination of 125 I did not markedly differ in the various experimental groups, the bulk of the activity being recovered in the urine. The intestine could not be ruled out as a major site of thymocyte loss. Since significant radiation or pharmacologic toxicity was unlikely with the doses of 125 IUdR used, the data indicated that the vast majority of newly formed thymocytes dies after a short life and only a small fraction of thymic migrants is longer lived

Bioprocessing feasibility analysis. [thymic hormone bioassay and electrophoresis

Science.gov (United States)

1978-01-01

The biology and pathophysiology of the thymus gland is discussed and a clinical procedure for thymic hormone assay is described. The separation of null lymphocytes from mice spleens and the functional characteristics of the cells after storage and transportation were investigated to develop a clinical procedure for thymic hormone assay, and to determine whether a ground-based approach will provide the desired end-product in sufficient quantities, or whether the microgravity of space should be exploited for more economical preparation of the hormone.

Flt3 ligand-receptor interaction is important for maintenance of early thymic progenitor numbers in steady-state thymopoiesis.

Science.gov (United States)

Kenins, Linda; Gill, Jason W; Holländer, Georg A; Wodnar-Filipowicz, Aleksandra

2010-01-01

T-cell production throughout life depends on efficient colonization and intrathymic expansion of BM-derived hematopoietic precursors. After irradiation-induced thymic damage, thymic recovery is facilitated by Flt3 ligand (FL), expressed by perivascular fibroblasts surrounding the thymic entry site of Flt3 receptor-positive progenitor cells. Whether intrathymic FL-Flt3 interactions play a role in steady-state replenishment of T cells remains unknown. Here, using competitive BM transplantation studies and fetal thymic organ cultures we demonstrated the continued numerical advantage of Flt3+ intrathymic T-cell precursors. Sub-kidney capsule thymic transplantation experiments, in which WT and FL-/- thymic lobes were grafted into FL-/- recipients, revealed that FL expression by the thymic microenvironment plays a role in steady-state thymopoiesis. The deficiency of the most immature thymic T-cell precursors correlated to upregulation of FL by thymic MTS15+ fibroblasts, suggesting that the number of Flt3+ progenitor cells may regulate the thymic expression of this cytokine. Together, these results show that FL expression by thymic stromal fibroblasts interacting with Flt3+ T-cell progenitors is important for the physiological maintenance of early T-cell development.

The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis

International Nuclear Information System (INIS)

Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E.

1997-01-01

The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs

Thymic hyperplasia - clinical course and imaging diagnostic

International Nuclear Information System (INIS)

Drebov, R.; Panov, M.; Totev, M.; Deliverski, T.; Tcandev, I.; Velkovski, I.

2006-01-01

The real thymic hyperplasia is benign disease sometimes simulating malignant tumours. The aim of this study is to analyse the clinical symptoms of real thymic hyperplasia and the results from imaging diagnostic based on our clinical material. Clinical material include 27 children, aged from two months to 15 years, admitted in department of thoracic surgery, for a period of 20 years (1985 - 2004). We retrospectively analyze the clinical signs and results from X-ray investigation, CT (Siemens Somatom DRG and Philips Secura) and echocardiography (Acuson TX, 5 and 7 MHz). We discuss the diagnostic value of different methods as well as typical and atypical findings. (authors)

Effect of allogenic thymic cells on radioleukaemogenesis in AKR-T1ALD mice

International Nuclear Information System (INIS)

Legrand, E.; Sankar-Mistry, P.; Kressmann, M.C.

1975-01-01

When AKR mice are irradiated with a sub-lethal dose (4 times 175 R), thymic lymphosarcomas (L.S.) occur earlier than in controls. This accelerated leukaemogenesis is not inhibited by syngenic restoration with bone marrows cells (BM). Using the AKR/T1ALD substrain which bears 38 chromosomes with 1 metacentric markers, it has been shown that AKR radio-chimaeras restored by T1ALD BM developed two kinds of L.S.: early (radiation-induced) L.S. originating mainly from host cells surviving irradiation and late L.S. from donor cells. The experiments were to investigate the potential influence of normal allogenic thymic cells, with or without syngenic B.M., on the incidence, latency and origin of LS appearing in irradiated AKR recipients. Adding C3H allogenic thymic cells to syngenic B.M. increases the percentage of early L.S. whose latencies are unchanged. Besides, when C3H thymic cells are injected to irradiated controls without syngenic B.M. cells, L.S. are seen to occur significantly earlier than in just the irradiated animals alone. In radio-chimaeras restored by allogenic thymic cells and syngenic B.M., except in one case, all the L.S. were seen to originate from B.M. cells. The interpretation of these results depends on the possible role of allogenic thymic cells on host cells surviving the irradiation, or the exogeneous B.M. In the first case, allogenic thymocytes could induce a graft versus host reaction increasing the post-irradiation depletion of lymphoid system and hastening thymic endoregeneration which is supposed to be the first step towards leukaemogenesis. The second hypothesis, which seems the most likely, would be that C1H thymic cells could selectively act on host cells surviving irradiation and enhance the differenciation of haemopoietic precursors at the expense of the lymphoid cells [fr

Radiation carcinogenesis in mouse thymic lymphomas

International Nuclear Information System (INIS)

Kominami, Ryo; Niwa, Ohtsura

2006-01-01

Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the ''indirect mechanism'' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility. (author)

Clinical analysis of thymic regrowth following chemotherapy in children and adolescents with malignant lymphoma

International Nuclear Information System (INIS)

Zhen Zijun; Sun Xiaofei; Xia Yi; Ling Jiayu; Cai Yue; Wang Juan; Guan Zhongzhen

2010-01-01

Thymic regrowth following chemotherapy has typical clinical and imaging manifestations that can be used to diagnose it prior to pathological diagnosis. We investigated methods for diagnosing thymic regrowth following chemotherapy with non-invasive methods. Our study included 26 children and adolescents with thymic regrowth following chemotherapy for malignant lymphoma. Computed tomography scans were routinely performed for follow-up observations. After the emergence of new mediastinal masses, patients either underwent Fluorine-18 fluorodeoxyglucose-positron emission tomography scans to identify the characteristics of the mass, or were closely followed up. Thymic regrowth occurred 1-12 months after the last chemotherapy (mean, 4 months). Computed tomography mostly revealed diffusely enlarged thymic parenchymatous tissues that maintained normal thymic morphology. Computed tomography values were 36.72±9.48 Hu and increased by 5.56±2.62 Hu in contrast enhancement. The mean volume of the mass was 19.2 cm 3 . Twenty patients underwent positron emission tomography; among them, five (25%) showed no intake of Fluorine-18 fluorodeoxyglucose in the anterior mediastinal mass, and 15 (75%) showed radioactivity distribution in the mass with a mean standardized uptake value of 2.7; the shape was regular and radioactivity distribution was uniform. The mean follow-up duration was 40 months and all patients achieved disease-free survival. In the absence of pathological diagnosis, thymic regrowth following chemotherapy can be diagnosed by clinical features combined with characteristic manifestations in computed tomography and positron emission tomography scans. (author)

Anti-apoptotic signature in thymic squamous cell carcinomas – functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

OpenAIRE

Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A.; Rieker, Ralf J.; Körner, Daniel; Nix, Wilfried; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

2016-01-01

The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might ...

Results of Definitive Chemoradiotherapy for Unresectable Esophageal Cancer

International Nuclear Information System (INIS)

Noh, O Kyu; Je, Hyoung Uk; Kim, Sung Bae

2008-01-01

To investigate the treatment outcome and failure patterns after definitive chemoradiation therapy in locally advanced, unresectable esophageal cancer. Materials and Methods: From February 1994 to December 2002, 168 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated by definitive chemoradiation therapy. External beam radiation therapy (EBRT) (42-46 Gy) was delivered to the region encompassing the primary tumor and involved lymph nodes, while the supraclavicular fossa and celiac area were included in the treatment area as a function of disease location. The administered cone-down radiation dose to the gross tumor went up to 54-66 Gy, while the fraction size of the EBRT was 1.8-2.0 Gy/fraction qd or 1.2 Gy/fraction bid. An optional high dose rate (HDR) intraluminal brachytherapy (BT) boost was also administered (Ir-192, 9-12 Gy/3 -4 fx). Two cycles of concurrent FP chemotherapy (5-FU 1,000 mg/m2/day, days 2-6, 30-34, cisplatin 60 mg/m2/day, days 1, 29) were delivered during radiotherapy with the addition of two more cycles. Results: One hundred sixty patients were analyzable for this review [median follow-up time: 10 months (range 1-149 months)]. The number of patients within AJCC stages I, II, III, and IV was 5 (3.1%), 38 (23.8%), 68 (42.5%), and 49 (30.6%), respectively. A HDR intraluminal BT was performed in 26 patients. The 160 patients had a median EBRT radiation dose of 59.4 Gy (range 44.4-66) and a total radiation dose, including BT, of 60 Gy (range 44.4-72), while 144 patients received a dose higher than 40 Gy. Despite the treatment, the disease recurrence rate was 101/160 (63.1%). Of these, the patterns of recurrence were local in 20 patients (12.5%), persistent disease and local progression in 61 (38.1%), distant metastasis in 15 (9.4%), and concomitant local and distant failure in 5 (3.1%). The overall survival rate was 31.8% at 2 years and 14.2% at 5 years (median 11.1 months). Disease-free survival was 29

Results of Definitive Chemoradiotherapy for Unresectable Esophageal Cancer

Energy Technology Data Exchange (ETDEWEB)

Noh, O Kyu; Je, Hyoung Uk; Kim, Sung Bae [Ulsan University College of Medicine, Seoul (Korea, Republic of)] (and others)

2008-12-15

To investigate the treatment outcome and failure patterns after definitive chemoradiation therapy in locally advanced, unresectable esophageal cancer. Materials and Methods: From February 1994 to December 2002, 168 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated by definitive chemoradiation therapy. External beam radiation therapy (EBRT) (42-46 Gy) was delivered to the region encompassing the primary tumor and involved lymph nodes, while the supraclavicular fossa and celiac area were included in the treatment area as a function of disease location. The administered cone-down radiation dose to the gross tumor went up to 54-66 Gy, while the fraction size of the EBRT was 1.8-2.0 Gy/fraction qd or 1.2 Gy/fraction bid. An optional high dose rate (HDR) intraluminal brachytherapy (BT) boost was also administered (Ir-192, 9-12 Gy/3 -4 fx). Two cycles of concurrent FP chemotherapy (5-FU 1,000 mg/m2/day, days 2-6, 30-34, cisplatin 60 mg/m2/day, days 1, 29) were delivered during radiotherapy with the addition of two more cycles. Results: One hundred sixty patients were analyzable for this review [median follow-up time: 10 months (range 1-149 months)]. The number of patients within AJCC stages I, II, III, and IV was 5 (3.1%), 38 (23.8%), 68 (42.5%), and 49 (30.6%), respectively. A HDR intraluminal BT was performed in 26 patients. The 160 patients had a median EBRT radiation dose of 59.4 Gy (range 44.4-66) and a total radiation dose, including BT, of 60 Gy (range 44.4-72), while 144 patients received a dose higher than 40 Gy. Despite the treatment, the disease recurrence rate was 101/160 (63.1%). Of these, the patterns of recurrence were local in 20 patients (12.5%), persistent disease and local progression in 61 (38.1%), distant metastasis in 15 (9.4%), and concomitant local and distant failure in 5 (3.1%). The overall survival rate was 31.8% at 2 years and 14.2% at 5 years (median 11.1 months). Disease-free survival was 29

Evidence That Androgens Modulate Human Thymic T Cell Output

Science.gov (United States)

Olsen, Nancy J.; Kovacs, William J.

2010-01-01

Background The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy. Methods Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells (PBMCs). Cells bearing T cell receptor excision circles (TRECs) were quantitated using real-time PCR amplification of DNA isolated from PBMCs from normal men and from hypogonadal men before and after testosterone replacement therapy. Results CD4+CD45+ (“naïve”) T cells comprised 10.5% of lymphocytes in normal males; this proportion was greatly increased in two hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4+CD45RA+ cells fell from 37.36% to 20.05% after one month and to 12.51% after 7 months of normalized androgen levels. In two hypogonadal patients TREC levels fell by 83% and 78% after androgen replacement therapy. Conclusions Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement. PMID:21218609

Spontaneous rupture of thymic neuroendocrine carcinoma: A case report

Energy Technology Data Exchange (ETDEWEB)

Park, Chan Yeong; Lee, In Jae; Min, Soo Kee [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

2015-11-15

Thymic neuroendocrine carcinoma (NEC) is a rare neoplasm with tendencies of local invasion and metastasis. Usually, it is detected incidentally or by its symptoms caused by mass effect. Rupture of the tumor is extremely rare. In this study, we report a case of a ruptured thymic NEC that was combined with a potentially fatal hemorrhage. This lesion was manifested as a progressive bulging of the right cardiac border on serial chest radiographs, and on CT as a large anterior mediastinal mass with heterogeneous enhancement, internal necrosis, and hematoma.

Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis

DEFF Research Database (Denmark)

Wendland, Kerstin; Niss, Kristoffer; Kotarsky, Knut

2018-01-01

Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis. In the abse......Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis...

Antiretroviral therapy increases thymic output in children with HIV

DEFF Research Database (Denmark)

Schou Sandgaard, Katrine; Lewis, Joanna; Adams, Stuart

2014-01-01

OBJECTIVE: Disease progression and response to antiretroviral therapy (ART) in HIV-infected children is different to that of adults. Immune reconstitution in adults is mainly from memory T cells, whereas in children it occurs predominantly from the naive T-cell pool. It is unclear however what...... with a recently described mathematical model to give explicit measures of thymic output. RESULTS: We found that age-adjusted thymic output is reduced in untreated children with HIV, which increases significantly with length of time on ART. CONCLUSION: Our results suggest that a highly active thymus in early...

Effect of Bcl11b genotypes and γ-radiation on the development of mouse thymic lymphomas

International Nuclear Information System (INIS)

Yoshikai, Yoshihiro; Sato, Toshihiro; Morita, Shinichi; Kohara, Yuki; Takagi, Ritsuo; Mishima, Yukio; Kominami, Ryo

2008-01-01

Bcl11b is a haploinsufficient tumor suppressor gene and expressed in many tissues such as thymus, brain and skin. Irradiated Bcl11b +/- heterozygous mice mostly develop thymic lymphomas, but the preference of Bcl11b inactivation for thymic lymphomas remains to be addressed. We produced Bcl11b +/- heterozygous and Bcl11b wild-type mice of p53 +/- background and compared their incidence of γ-ray induced thymic lymphomas. Majority of the tumors in p53 +/- mice were skin tumors, and only 5 (36%) of the 14 tumors were thymic lymphomas. In contrast, Bcl11b +/- p53 +/- doubly heterozygous mice developed thymic lymphomas at the frequency of 27 (79%) of the 34 tumors developed (P = 0.008). This indicates the preference of Bcl11b impairment for thymic lymphoma development. We also analyzed loss of the wild-type alleles in the 27 lymphomas, a predicted consequence given by γ-irradiation. However, the loss frequency was low, only six (22%) for Bcl11b and five (19%) for p53. The frequencies did not differ from those of spontaneously developed thymic lymphomas in the doubly heterozygous mice, though the latency of lymphoma development markedly differed between them. This suggests that the main contribution of irradiation at least in those mice is not for the tumor initiation by inducing allelic losses but probably for the promotion of thymic lymphoma development

Comparison of Outcomes for Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Treated With Induction Chemotherapy Followed By Concurrent Chemoradiation vs. Concurrent Chemoradiation Alone

International Nuclear Information System (INIS)

Huang, Eugene H.; Liao Zhongxing; Cox, James D.; Guerrero, Thomas M.; Chang, Joe Y.; Jeter, Melinda; Borghero, Yerko; Wei Xiong; Fossella, Frank; Herbst, Roy S.; Blumenschein, George R.; Moran, Cesar; Allen, Pamela K.; Komaki, Ritsuko

2007-01-01

Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) treated at our institution with concurrent chemoradiation with or without induction chemotherapy. Methods and Materials: We retrospectively analyzed 265 consecutive patients who received definitive treatment with three-dimensional conformal radiation and concurrent chemotherapy. Of these, 127 patients received induction chemotherapy before concurrent chemoradiation. Results: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, weight loss, histology, grade, and stage. Patients who received induction chemotherapy had better overall survival (median, 1.9 vs. 1.4 years; 5-year rate, 25% vs. 12%; p < 0.001) and distant metastasis-free survival (5-year rate, 42% vs. 23%; p = 0.021). Locoregional control was not significantly different between the two groups. Multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival, with a hazard ratio of 0.55 (95% confidence interval 0.40-0.75; p < 0.001). A planned subgroup analysis showed that induction chemotherapy was associated with a significant overall survival benefit for patients with adenocarcinoma or large-cell carcinoma (5-year rate, 24% vs. 8%; p = 0.003) but not for those with squamous cell carcinoma. A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival, with a hazard ratio of 0.47 (95% confidence interval, 0.28-0.78; p = 0.003). Conclusion: Our retrospective analysis suggests that in combination with concurrent chemoradiation, induction chemotherapy may provide a small but significant survival benefit for patients with unresectable locally advanced adenocarcinoma or large-cell carcinoma of the lung

Modification of radiation-induced murine thymic lymphoma incidence by curcumin

International Nuclear Information System (INIS)

Dange, P.S.; Yadav, H.D.; Kumar, Vimalesh; Bhilwade, H.N.; Pandey, B.N.; Sarma, H.D.

2017-01-01

Curcumin is a known antioxidant, preventing radiation damage including carcinogenesis. However, concentration and feeding schedule of curcumin in modification of radiation induced thymic lymphoma incidence in vivo model has not been studied. We report here modification of incidence of γ-radiation-induced thymic lymphoma in mice fed with different doses of curcumin (0.05 to 1 %) in diet. Results: Female Swiss mice (6-8 weeks) fed with normal diet and exposed to 3 Gy whole body "6"0Co γ-irradiation (WBI) showed 85 % incidence of thymic lymphoma (TL) at 120 days post-irradiation. A concentration of 1 % curcumin was found the most effective in TL incidence prevention than other fed concentrations. The TL incidence was remarkably reduced when curcumin was fed to the mice before than after the radiation exposure. These results suggest modification of TL incidence by curcumin in irradiated mice involving DNA damage and apoptotic death mechanisms

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

Directory of Open Access Journals (Sweden)

Chien Chih-Yen

2011-03-01

Full Text Available Abstract Background This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1 expression on response to cisplatin-based induction chemotherapy (IC followed by concurrent chemoradiation (CCRT in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC patients. Methods Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records. Results The 12-month progression-free survival (PFS and 2-year overall survival (OS rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p Conclusions Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.

Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration

Science.gov (United States)

Wertheimer, Tobias; Velardi, Enrico; Tsai, Jennifer; Cooper, Kirsten; Xiao, Shiyun; Kloss, Christopher C.; Ottmüller, Katja J.; Mokhtari, Zeinab; Brede, Christian; deRoos, Paul; Kinsella, Sinéad; Palikuqi, Brisa; Ginsberg, Michael; Young, Lauren F.; Kreines, Fabiana; Lieberman, Sophia R.; Lazrak, Amina; Guo, Peipei; Malard, Florent; Smith, Odette M.; Shono, Yusuke; Jenq, Robert R.; Hanash, Alan M.; Nolan, Daniel J.; Butler, Jason M.; Beilhack, Andreas; Manley, Nancy R.; Rafii, Shahin; Dudakov, Jarrod A; van den Brink, Marcel RM

2018-01-01

The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. Here we show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration, via their production of BMP4. ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signalling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of Foxn1, a key transcription factor involved in TEC development, maintenance and regeneration; and its downstream targets such as Dll4, itself a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity. PMID:29330161

Studies on radiation-induced thymic lymphomagenesis in B10 strain mice

International Nuclear Information System (INIS)

Muto, Masahiro

1989-01-01

Using B10.Thy 1 congenic strain mice, we reexamined the earlier results by Kaplan and others that lymphomas could develop from lymphocytes present in the nonirradiated parental thymuses grafted into thymectomized, fractionally irradiated H-2 semiincompatible recipient mice. The results indicated that 37 out of 91 thymectomized and irradiated B10.Thy 1.2 mice developed lymphomas of which 75 % were shown to have originated from grafted thymuses. The evidence was not obtained that supported the involvement of endogenous MuLV or some kind of transmissible agents during thymic lymphomagenesis. We found, with intrathymic injection assay, that 'preneoplastic' cells that will eventually develop into thymic lymphomas under the influence of thymic microenvironment first appeared in the thymuses about 4-8 days after irradiation. These thymic prelymphoma cells 'thymus-dependent' preneoplastic cells were detected in 26.1 % of the test donor thymuses when examined at 14 days and in more than 63 % 21 and 31 days after irradiation. It was found that lymphomagenic irradiation resulted in the anomalous appearance of CD4 + and/or CD8 + thymocytes bearing IL-2 receptor (IL-2R) which were different from normal thymocyte subpopulations. Thymic prelymphoma cells existed mainly in CD4 - CD8 - and CD4 - CD8 + thymocyted subpopulations and also in CD4 + CD8 + subpopulation. T cell lymphomas derived from CD4 - CD8 - prelymphoma cells had mainly CD4 - CD8 - or CD4 - CD8 + phenotypes. T cell lymphomas developed from CD4 - CD8 + prelymphoma cells mainly expressed CD4 - CD8 + or CD4 + CD8 + phenotype. T cell lymphomas originated from CD4 + CD8 + prelymphoma cells were mainly CD4 + CD8 + but some CD4 - CD8 + or CD4 + CD8 - cells were also present. These T cell lymphomas expressed IL-2R on various levels. The development of thymic prelymphoma cells is discussed in view of thymocyte differentiation. (J.P.N)

Thyroid and thymic exeresis in surgery of hyperparathyroidism.

Science.gov (United States)

Diaconescu, Mr; Glod, M; Costea, I; Grigorovici, M; Diaconescu, S

2014-01-01

Owing to close anatomical and embryological connexions between the thyroid, parathyroids and thymus,manifold coexisting pathology can be identified during the surgery of hyperparathyroidism (Hp). In this retrospective study we report the incidence, clinical forms, histology and management of thyroid and thymic synchronous lesions encountered in as eries of 82 consecutive patients with various types of Hp operated on in the last three decades. Demography, clinical records, biochemical data, imaging procedures, pathology reports and surgical protocols were revised. Between 1984-2013, 82 cases of Hp, 20 primary and 62 renal (27 secondary and 35 tertiary), 57 women and 25 males (sex ratio: 2.3 1) of 15-72 (mean 46.5) years, under went surgery in our clinic. Concomitant thyroid exereses were performed in 32 patients (2 subtotal thyroidectomies, 12 lobectomies, 8 atypical resections and 10 diagnosis biopsies), foruni- or bilateral (multi)nodular goiters or different €œminutelesions. Pathology showed 11 colloid goiters, 3 follicular adenomas,5 nodular hyperplasias and 6 thyroiditis cases, 3 papillary microcarcinomas and 4 specimens with normal thyroid tissue.Excision of the fibrofatty retromanubrial tissue in total parathyroidectomies for renal Hp (19 cases) revealed one nonmyastenicthymoma, one thymic cyst and thymic remnants in 6 patients.Morbidity in these extended operations was not significantly increased, comparing to the parathyroid exploration alone. Meticulous pre- and intraoperative evaluation in all cases of Hp enables the actual shift from bilateral neck exploration to minimally invasive surgery,increasing however the potential risk of missing thyroid or thymic coexistent significant lesions. The surgeon dedicated to this pathology must be aware of the possibility of encountering such synchronous association and make generous efforts to wards their complete cure in a single operation. Celsius.

External beam radiotherapy for unresectable pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Kagami, Yoshikazu; Nishio, Masamichi; Narimatsu, Naoto; Ogawa, Hajime; Betsuyaku, Takashi; Hirata, Kouji; Ikeda, Shigeyuki (Sapporo National Hospital (Japan). Hokkaido Cancer Center)

1992-04-01

Between 1980 to 1989, 24 patients with unresectable pancreatic cancer (10 with localized tumor alone and 14 with distant metastases) have been treated with external beam radiation at Sapporo National Hospital, Hokkaido Cancer Center. Response rate of pancreatic tumor treated with external beam radiation was 33.3% (7/21) with no complete response. Median survival time of the patients with localized tumor was 10 months and that of the patients with distant metastases was 3 months. Relief of pain occurred in 92.9% (12/13) of patients having pain due to pancreatic tumor and in 75% (3/4) of patients having pain due to bone metastases. Major complication was gastric ulcer which developed in 5 patients of 21 patients given stomach irradiation. We concluded that unresectable pancreatic cancer would be frequently indicated for radiotherapy. (author).

Development of Thymic Epithelial Cells

DEFF Research Database (Denmark)

Ulyanchenko, Svetlana; Vaidya, Harsh J.; O'Neill, Kathy E.

2016-01-01

The thymus is the primary lymphoid organ in which the T cell repertoire is generated. The complex cellularity of this organ is uniquely designed to facilitate T cell development: defects in thymus development or function can cause immunodeficiencies ranging from the absence of T cell-mediated imm......The thymus is the primary lymphoid organ in which the T cell repertoire is generated. The complex cellularity of this organ is uniquely designed to facilitate T cell development: defects in thymus development or function can cause immunodeficiencies ranging from the absence of T cell......-mediated immunity to broad-spectrum autoimmune disease. Peak thymus size and output occurs early in life, after which the thymus undergoes a natural process of involution. This results in the progressive loss of functional thymus tissue and correspondingly in decreased production of new naïve T cells with age...... - contributing to the diminished capacity of the aged immune system to adequately respond to new antigenic challenge. Age-related thymic involutions, together with the thymic involutions associated with cytotoxic therapies (e.g., radio- or chemotherapy), have raised interest in development of clinically useful...

Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours.

Science.gov (United States)

Kajiura, Koichiro; Takizawa, Hiromitsu; Morimoto, Yuki; Masuda, Kiyoshi; Tsuboi, Mitsuhiro; Kishibuchi, Reina; Wusiman, Nuliamina; Sawada, Toru; Kawakita, Naoya; Toba, Hiroaki; Yoshida, Mitsuteru; Kawakami, Yukikiyo; Naruto, Takuya; Imoto, Issei; Tangoku, Akira; Kondo, Kazuya

2017-09-01

Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET. Copyright © 2017 Elsevier B.V. All rights reserved.

A rear case of multilocular thymic cyst with follicular lymphoid hyperplasia; Radiologic and histopathologic features

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Suk; Cha, Eun Jung [Konyang University Hospital, Daejeon (Korea, Republic of)

2016-06-15

Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose.

Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System

Directory of Open Access Journals (Sweden)

Raul Vizcardo

2018-03-01

Full Text Available Summary: Induced pluripotent stem cell (iPSC-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs. iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies. : A barrier for clinical application of iPSC-derived CD8 T cells using OP9/DLL1 is their abnormal biology. Vizcardo et al. show that a 3D thymic culture system enables the generation of a homogeneous antigen-specific T cell subset, named iTEs, which closely mimics naive T cells and exhibits potent anti-tumor activity. Keywords: thymopoiesis, T cell differentiation, iPSC differentiation, adoptive cell transfer, naïve T cell, recent rhymic emigrants, fetal thymus organ culture, immunotherapy, 3D culture, tumor antigen specific T cell

Elevation of oleate-activated phospholipase D activity during thymic atrophy

Science.gov (United States)

Lee, Youngkyun; Song, Soo-Mee; Park, Heung Soon; Kim, Sungyeol; Koh, Eun-Hee; Choi, Myung Sun; Choi, Myung-Un

2002-01-01

Various phospholipases are thought to be associated with the in vitro apoptosis of thymocytes. In the present study, the in vivo phospholipase D (PLD) activity of rat thymus was studied after whole-body X-irradiation or injection of dexamethasone (DEX). Using exogenous [14C]dipalmitoyl phosphatidylcholine (PC) as the substrate, an elevation of oleate-activated PLD activity was observed during thymic atrophy. The activity increases were sevenfold at 48 hr after 5-Gy irradiation and fourfold at 72 hr after injection of 5 mg/kg DEX. The elevation of PLD activity appeared to parallel extensive thymus shrinkage. An increased level of thymic phosphatidic acid (PA), the presumed physiological product of PLD action on PC, was also detected. By comparing the acyl chains of PA with those of other phospholipids, PA appeared to originate from PC. To assess the role of PLD during thymic atrophy, thymocytes and stromal cells were isolated. Although thymocytes themselves exhibited significant PLD activation, the major elevation in PLD activity (greater than fourfold) was found in isolated stromal cells. PLD was also activated during in vitro phagocytosis of apoptotic thymocytes by the macrophage-like cell line P388D1. This in vitro phagocytosis was significantly inhibited by PLD action blockers, such as 2,3-diphosphoglycerate and 1-butanol. These observations strongly suggest that the alteration of oleate-activated PLD activity is part of an in vivo event in the progression of thymic atrophy, including phagocytic clearance of apoptotic thymocytes. PMID:12460188

Anti-apoptotic signature in thymic squamous cell carcinomas - functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

Directory of Open Access Journals (Sweden)

Bei eHuang

2013-12-01

Full Text Available The molecular pathogenesis of thymomas and thymic carcinomas (TCs is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCC with a custom made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

Chemoradiation for unresectable gall bladder cancer: time to review historic nihilism?

Science.gov (United States)

Engineer, Reena; Wadasadawala, Tabassum; Mehta, Shaesta; Mahantshetty, Umesh; Purandare, Nilendu; Rangarajan, Venkatesh; Kishore Shrivastava, Shyam

2011-12-01

Treatment of unresectable locally advanced gallbladder cancers (LAGBC) usually consists of various palliative strategies which provide only a modest survival benefit. Here, we present a series of three patients of LAGBC-treated consecutively at our center with preoperative chemoradiation using tomotherapy and concurrent gemcitabine. All three cases were reported to be adenocarcinoma by biopsy or fine-needle aspiration cytology. All the patients underwent positron emission tomography with computerized tomography scan to rule out distant metastasis and also to map the extent of disease for radiotherapy planning. Preoperative chemoradiation consisted of gemcitabine at 300 mg/m(2) weekly and tomotherapy with daily image guidance with MVCT over 5 weeks to a dose of 57 Gy in 25 fractions to the gross tumor and 45 Gy in 25 fractions to the clinical target volume to cover the areas of microscopic spread. Complete metabolic and radiologic response was observed for 2 patients and partial response for 1 patient. Two patients underwent complete surgical excision of which 1 patient had complete pathological response and 1 patient had small residual tumor at the primary and no nodal metastasis. The third patient could not undergo surgery due to medical reasons. The clinical outcome for unresectable LAGBC with preoperative chemoradiation in terms of feasibility, safety, and survival is encouraging. This treatment strategy has a curative potential for the otherwise fatal disease.

Genetic Regulation of Development of Thymic Lymphomas Induced by N‐Propyl‐N‐nitrosourea in the Rat

Science.gov (United States)

Fukami, Hiroko; Nishimura, Mayumi; Matsuyama, Mutsushi

1995-01-01

To clarify the linkage between Hbb and Tls‐1 (thymic lymphoma susceptible‐1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of N‐propyl‐N‐nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6 genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls‐1 loci could be demonstrated since WKY rats also developed a high incidence of thymic lymphomas in response to PNU. Nevertheless, thymic lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large tumor growth phenotype, while the [(WKY × BUF) × WKY] backcross generation consisted of rats with either rapidly growing or slowly growing tumors. It was thus concluded that rapid development of thymic lymphomas is determined by a gene, provisionally designated Tls‐3. Analysis of the relationship between 6 genetic markers and development of thymic lymphoma in the backcross generation demonstrated that the Tls‐3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls‐3 may not be identical with Tls‐1 and other genes known to be relevant to thymic tumors, but its relationship with Tls‐2 remains obscure. PMID:7559080

Acute respiratory failure revealing a multilocular thymic cyst in an infant: a case report.

Science.gov (United States)

Asma, Bouziri; Ammar, Khaldi; Khaled, Menif; Najoua, Guandoura; Nejla, Ben Jaballah

2009-11-30

Multilocular thymic cysts are rare benign lesions of the neck and mediastinum that can occur at any age. In children, multilocular thymic cysts are usually symptomatic after the age of 2 years and produce few symptoms. We present an unusual case of a multilocular thymic cyst diagnosed in a 3-month-old girl and causing severe respiratory failure. A 3 month-old-girl, with a medical history of dyspnea and wheezing since the age of 20 days, presented in our pediatric intensive care unit for acute respiratory failure requiring mechanical ventilation. The chest radiograph showed thoracic distension without any other abnormalities. The diagnosis of severe asthma was initially suspected and the patient was treated by intravenous corticosteroids and continuous perfusion of salbutamol without any improvement. A chest tomography scan was performed and demonstrated an anterior mediastinal multiseptated cystic mass extending from the inferior face of the thyroid gland to the left cardiophrenic angle. Sternotomy and excision biopsy were planned urgently. The cystic mass was excised completely. The histopathological examination confirmed the diagnosis of a multilocular thymic cyst. The particularities of our observation are the occurrence of a multilocular thymic cyst in a young infant and its presentation by a severe acute respiratory failure mimicking asthma.

Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice

International Nuclear Information System (INIS)

Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y.; Yan, Mingshan

2009-01-01

Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/- mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.

CT features of the subtypes of thymic epithelial tumors on the basis of the world health organization classification

International Nuclear Information System (INIS)

Guo Xiaoyu; Yu Hong; Xiao Xiangsheng

2013-01-01

Thymic epithelial tumors including thymomas and thymic carcinomas have well-known heterogeneous oncologic behaviors and variable histologic features. They show variable and unpredictable evolutions ranging from an indolent non-invasive feature to a highly infiltrative and metastasising one. Currently, CT is a common and efficient imaging method for assessing thymic epithelial tumors. CT evaluation is the main reference for preoperative clinic staging and histological classification. CT features of subtypes of thymic epithelial tumors on the basis of the World Health Organization classification provide the foundation for the diagnosis and predicting prognosis. (authors)

PICTORIAL ESSAY Thymic masses: A radiological review

African Journals Online (AJOL)

On chest X-ray, thymic abnormalities typically manifest as focal or diffuse ... Department of Radiodiagnosis and Imaging, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India. Corresponding author: B ... are considered of primary mediastinal origin if there is neither a detectable gonadal primary nor.

The Role of Radiation Therapy in the Unresectable Rectal Cancers

International Nuclear Information System (INIS)

Kim, Woo Cheol; Seong, Jin Sil; Kim, Gwi Eon

1995-01-01

Purpose : Unresectable rectal cancer has a grave prognosis, regardless of the therapy used and median survival is less than 1 year. Also, it is reported by many authors that 50-80% of unresectable lesions were rendered respectable by radiation therapy and the median survival time for the completely resected patients were better than that of the unresected patients. So we analyzed retrospectively our data for the better treatment outcome in these patients. Materials and Methods : From 1980 to 1992, 45 patients with initially unresectable tumors in the rectum were treated with radiation therapy with/without surgery in Department of Radiation Oncology, Yonsei Cancer Center. 10 MV radiation and multiple field technique( box or AP/PA) were used. The total dose was 8-70 Gy and median dose was 48 Gy. We evaluated the lesion status at 45-50 Gy for operability. If the lesions appeared to be respectable, the patients were operated on 4-6 weeks after radiation therapy. But if the lesions were still fixed, the radiation dose was increased to 60-65 Gy. Results : For all patients, the 2-year actuarial survival was 13.3% and median survival was 9.5 months. Of 6 patients who had received less than 45 Gy, only 17% of patients responded, but in the patients who had received more than 45 Gy, 60% of response rate was achieved. Six of the 24 patients(25%) underwent surgical resections following RT. For patients undergoing curative resection, the two-year survival was 50%, but that of the patients without resection was 9.5% (p<0.01). Survival of patients with complete response following RT was 50% at 2 years. Survival of patients with partial response, stable disease and progressive disease after RT was 13.4%, 15.4%, 0% respectively (p<0.05). Conclusion: Our data suggests that the efforts which can increase the response rate and aggressive surgical approach are needed to achieve the better local control and survival in unresectable rectal cancers

[Impact of thymic function in age-related immune deterioration].

Science.gov (United States)

Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

2013-01-01

Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

Interaction between thymic cells and hemopoietic stem cells. Enhanced repopulation of the irradiated thymus

International Nuclear Information System (INIS)

Daculsi, Richard; Legrand, Elisabeth; Duplan, J.-F.

1977-01-01

In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells [fr

Lymphocyte depletion in thymic nurse cells: a tool to identify in situ lympho-epithelial complexes having thymic nurse cell characteristics

NARCIS (Netherlands)

Leene, W.; de Waal Malefijt, R.; Roholl, P. J.; Hoeben, K. A.

1988-01-01

In situ pre-existing complexes of epithelial cells and thymocytes having thymic nurse cell characteristics were visualized in the murine thymus cortex using dexamethasone as a potent killer of cortisone-sensitive thymocytes. The degradation and subsequent depletion of cortisone-sensitive thymocytes

Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling (Review).

Science.gov (United States)

Yan, Fenggen; Mo, Xiumei; Liu, Junfeng; Ye, Siqi; Zeng, Xing; Chen, Dacan

2017-11-01

The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress‑mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.

Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1

Directory of Open Access Journals (Sweden)

Dhalapathy Sadacharan

2013-01-01

Full Text Available Thymic neuroendocrine (NE tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1. They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT at the time of parathyroid surgery for primary hyperparathyroidism (PHPT in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting.

Clinical results of radiation therapy for thymic tumors

Energy Technology Data Exchange (ETDEWEB)

Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, Masaji; Fushiki, Masato

1991-12-01

From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author).

Clinical results of radiation therapy for thymic tumors

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki; Takahashi, Masaji; Fushiki, Masato.

1991-01-01

From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author)

Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

Energy Technology Data Exchange (ETDEWEB)

Deneve, Jeremiah L., E-mail: Jeremiah.Deneve@Moffitt.org [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States); Choi, Junsung [Moffitt Cancer Center, Department of Interventional Radiology (United States); Gonzalez, Ricardo J.; Conley, Anthony P.; Stewart, Steven; Han, Dale [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States); Werner, Philip; Chaudhry, Tariq A. [Moffitt Cancer Center, Department of Anesthesia (United States); Zager, Jonathan S., E-mail: Jonathan.Zager@Moffitt.org [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States)

2012-12-15

Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significant improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.

Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

International Nuclear Information System (INIS)

Deneve, Jeremiah L.; Choi, Junsung; Gonzalez, Ricardo J.; Conley, Anthony P.; Stewart, Steven; Han, Dale; Werner, Philip; Chaudhry, Tariq A.; Zager, Jonathan S.

2012-01-01

Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significant improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.

Application values of 99mTc-methoxyisobutylisonitrile imaging for differentiating benign and malignant thymic masses.

Science.gov (United States)

Lu, Chenghui; Wang, Xufu; Liu, Bin; Liu, Xinfeng; Wang, Guoming; Zhang, Qin

2017-08-01

The aim of the present study was to investigate the application value of 99m Tc-methoxyisobutylisonitrile (MIBI) imaging to differentiate between benign and malignant thymic masses. A total of 32 patients with space-occupying mediastinal masses were enrolled and early and delayed-phase images were collected following injection with the imaging agent. The tumor to background ratio (T/N) values at the different phases were also recorded. The sensitivity of the qualitative analysis to distinguish between benign and malignant thymic masses was 95.24%, with specificity as 90.91%. The T/N values in the early and delayed phases were not significantly different in the group with benign thymic masses, but demonstrated statistical significant differences in the groups with low- and intermediate-grade malignant thymic masses. The T/N values at the above early and delayed phase were significantly different between the benign and low-grade malignancy groups, as well as between low- and moderate-grade malignancy groups. Those between the benign and moderate-grade malignancy groups demonstrated no significant difference. 99m Tc-MIBI imaging was able to differentiate between benign and malignant thymic masses, and the simultaneous semi-quantitative analysis of the T/N values of the tumors may be able to initially determine the degree of malignancy of thymoma.

Chest roentgenographic findings of thymic size and shape in respiratory distress syndrome

International Nuclear Information System (INIS)

Oh, Young Ho; Yoon, Sung Do; Sung, Ki Yeal; Park, Seog Hee; Kim, Jong Woo; Bahk, Yong Whee

1984-01-01

Thymic size can be affected by both exogenous and endogenous glucocorticoids. Development of the respiratory distress syndrome (RDS) is influenced by adrenal cortical function. Thus, thymic size in RDS is considered to be enlarged due to decreased adrenal cortical function. To find whether the presence of RDS correlates with the thymus, the size and shape of the thymus were evaluated in the radiographs of premature infants with RDS, without RDS (control prematurity) and normal infants. The subjects were consisted of chest films of Korean premature infants, 120 with RDS, 60 without RDS, and 60 of normal infants taken at the Department of Radiology, Our Lady of Mercy Hospital during the period of 62 months since January 1978. Relative size of the thymus was determine by cardiothymic/thoracic ratio (CT /T ratio). Grading and location of the thymic prominence as well as incidence of the shape were examined. And all the relations among the radiographs of RDS, control prematurity and normal infants were analyzed. The results were as follows: 1. The CT/T ratio of premature infants with RDS was significantly greater than that of control prematurity and normal infants (P< 0.01). 2. The incidence of bilateral thymic prominence was more frequent in premature infant with RDS than in control prematurity and normal infants (P<0.05). 3. The frequency of thymic prominence was greater in the right than left side in all the three groups (P<0.05). 4. As in the shape of the thymus, a rounded type was most frequent, and a triangular type was least frequent in all three groups. 5. Incident of RDS was very low (9.8%) when the CT/T ratio is below 0.3 and it was very high (90.9%) when the CT/T ratio is above 0.49.

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

International Nuclear Information System (INIS)

Seong, Jinsil; Cho, Jae Ho; Kim, Nam Kyu; Min, Jin Sik; Suh, Chang Ok

2001-01-01

Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). Conclusion: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer

Volume-based quantification using dual-energy computed tomography in the differentiation of thymic epithelial tumours: an initial experience

Energy Technology Data Exchange (ETDEWEB)

Chang, Suyon; Hur, Jin; Im, Dong Jin; Suh, Young Joo; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Choi, Byoung Wook [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Han, Kyunghwa [Yonsei University College of Medicine, Yonsei Biomedical Research Institute, Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Kim, Dae Joon; Lee, Chang Young [Yonsei University College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of); Shin, Ha Young [Yonsei University College of Medicine, Department of Neurology, Seoul (Korea, Republic of)

2017-05-15

To investigate the diagnostic value of dual-energy computed tomography (DECT) in differentiating between low- and high-risk thymomas and thymic carcinomas. Our institutional review board approved this study, and patients provided informed consent. We prospectively enrolled 37 patients (20 males, mean age: 55.6 years) with thymic epithelial tumour. All patients underwent DECT. For quantitative analysis, two reviewers measured the following tumour parameters: CT attenuation value in contrast Hounsfield units (CHU), iodine-related HU and iodine concentration (mg/ml). Pathological results confirmed the final diagnosis. Of the 37 thymic tumours, 23 (62.2 %) were low-risk thymomas, five (13.5 %) were high-risk thymomas and nine (24.3 %) were thymic carcinomas. According to quantitative analysis, iodine-related HU and iodine concentration were significantly different among low-risk thymomas, high-risk thymomas and thymic carcinomas (median: 29.78 HU vs. 14.55 HU vs. 19.95 HU, p = 0.001 and 1.92 mg/ml vs. 0.99 mg/ml vs. 1.18 mg/ml, p < 0.001, respectively). DECT using a quantitative analytical method based on iodine concentration measurement can be used to differentiate among thymic epithelial tumours using single-phase scanning. (orig.)

Thymic hyperplasia in a patient with Grave's disease.

Science.gov (United States)

Hamzaoui, Amira A; Klii, Rim R; Salem, Randa R; Kochtali, Ines I; Golli, Mondher M; Mahjoub, Silvia S

2012-02-09

Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.

Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens

Directory of Open Access Journals (Sweden)

Sergio Cepeda

2018-01-01

Full Text Available Although autoimmune disorders are a significant source of morbidity and mortality in older individuals, the mechanisms governing age-associated increases in susceptibility remain incompletely understood. Central T cell tolerance is mediated through presentation of self-antigens by cells constituting the thymic microenvironment, including epithelial cells, dendritic cells, and B cells. Medullary thymic epithelial cells (mTECs and B cells express distinct cohorts of self-antigens, including tissue-restricted self-antigens (TRAs, such that developing T cells are tolerized to antigens from peripheral tissues. We find that expression of the TRA transcriptional regulator Aire, as well as Aire-dependent genes, declines with age in thymic B cells in mice and humans and that cell-intrinsic and cell-extrinsic mechanisms contribute to the diminished capacity of peripheral B cells to express Aire within the thymus. Our findings indicate that aging may diminish the ability of thymic B cells to tolerize T cells, revealing a potential mechanistic link between aging and autoimmunity.

A Whole-Tumor Histogram Analysis of Apparent Diffusion Coefficient Maps for Differentiating Thymic Carcinoma from Lymphoma.

Science.gov (United States)

Zhang, Wei; Zhou, Yue; Xu, Xiao-Quan; Kong, Ling-Yan; Xu, Hai; Yu, Tong-Fu; Shi, Hai-Bin; Feng, Qing

2018-01-01

To assess the performance of a whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating thymic carcinoma from lymphoma, and compare it with that of a commonly used hot-spot region-of-interest (ROI)-based ADC measurement. Diffusion weighted imaging data of 15 patients with thymic carcinoma and 13 patients with lymphoma were retrospectively collected and processed with a mono-exponential model. ADC measurements were performed by using a histogram-based and hot-spot-ROI-based approach. In the histogram-based approach, the following parameters were generated: mean ADC (ADC mean ), median ADC (ADC median ), 10th and 90th percentile of ADC (ADC 10 and ADC 90 ), kurtosis, and skewness. The difference in ADCs between thymic carcinoma and lymphoma was compared using a t test. Receiver operating characteristic analyses were conducted to determine and compare the differentiating performance of ADCs. Lymphoma demonstrated significantly lower ADC mean , ADC median , ADC 10 , ADC 90 , and hot-spot-ROI-based mean ADC than those found in thymic carcinoma (all p values histogram analysis of ADC maps can improve the differentiating performance between thymic carcinoma and lymphoma.

Micronodular thymic neoplasms: case series and literature review with emphasis on the spectrum of differentiation.

Science.gov (United States)

Mneimneh, Wadad S; Gökmen-Polar, Yesim; Kesler, Kenneth A; Loehrer, Patrick J; Badve, Sunil

2015-11-01

We report nine cases of micronodular thymoma with lymphoid B-cell hyperplasia and one case of micronodular thymic carcinoma with lymphoid hyperplasia from our institution. For a better understanding of these rare tumors, clinical records, and histological features of these cases were reviewed, with detailed review of additional 64 literature cases of micronodular thymic neoplasms. The joint analysis identified 64 cases of micronodular thymoma with lymphoid B-cell hyperplasia and 9 cases of micronodular thymic carcinoma with lymphoid hyperplasia. Both groups revealed slight male predilection, with male:female ratio of 1.3:1 and 5:4, and occurred at >40 years of age, with a mean of 64 (41-83) and 62 (42-78) years, respectively. Myasthenia gravis was noted in 3/64 (5%) and 1/9 (11%) patients, respectively. Other systemic, disimmune, or hematologic disorders were noted in 6/64 (9%) and 1/9 (11%) patients, respectively. Components of conventional thymoma were reported in 11/64 (17%) micronodular thymomas with lymphoid B-cell hyperplasia, with transitional morphology between the two components in most of them. Cellular morphology was predominantly spindle in micronodular thymoma with lymphoid B-cell hyperplasia when specified (30/43), and epithelioid in micronodular thymic carcinoma with lymphoid hyperplasia (6/9), and cytological atypia was more encountered in the latter. Dedifferentiation/transformation from micronodular thymoma with lymphoid B-cell hyperplasia to micronodular thymic carcinoma with lymphoid hyperplasia seems to occur in a small subset of cases. Three cases of micronodular thymomas with lymphoid B-cell hyperplasia were described with co-existent low-grade B-cell lymphomas. Follow-up data were available for 30 micronodular thymomas with lymphoid B-cell hyperplasia and 6 micronodular thymic carcinomas with lymphoid hyperplasia, with a mean of 47 (0.2-180) months and 23 (3-39) months, respectively. Patients were alive without disease, except for five

Doubling time of thymic epithelial tumours on CT: correlation with histological subtype

Energy Technology Data Exchange (ETDEWEB)

Choe, Jooae; Lee, Sang Min; Kim, Namkug; Do, Kyung-Hyun; Seo, Joon Beom [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Songpa-gu, Seoul (Korea, Republic of); Lim, Soyeoun [Ulsan University Hospital, Department of Radiology, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Choi, Se Hoon [University of Ulsan College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of)

2017-10-15

We retrospectively evaluated the doubling time (DT) of thymic epithelial tumours (TET) according to the histological subtype on CT. From January 2005 to June 2016, we enrolled 53 patients who had pathologically confirmed TET and at least two CT scans. Tumour size was measured using a two-dimensional method, and the DT was calculated. DTs were compared among histological subtypes, and factors associated with rapid tumour growth (DT <180 days) were assessed. In 42 of the 53 patients (79.2%) the tumours showed interval growth (>2 mm) during follow-up. The median DT for all tumours was 400 days (range 48-1,964 days). There were no significant differences in DT in relation to histological subtype (p = 0.177). When TETs were recategorized into three groups, i.e. low-risk thymomas (types A, AB, B1), high-risk thymomas (types B2, B3), and thymic carcinoma, DT was significantly different among the groups (median DT 436, 381 and 189 days, respectively; p = 0.031). Histological subtype (type B3 and thymic carcinoma) was the single independent predictor of rapid tumour growth. The majority of TETs grew during follow-up with variable and relatively slow growth rates. Histological features of aggressive behaviour significantly correlated with a decreased DT and rapid growth. circle The majority of thymic epithelial tumours grew during follow-up (79.2%, 42/53). (orig.)

Bilateral cervical ectopic thymic nodules with accessory thyroid tissue and an ectopic parathyroid in the neck region

Directory of Open Access Journals (Sweden)

Wea-Lung Lin

2011-03-01

Full Text Available Some remnants of thymic tissue may be deposited along the pathway of the descent of the neck during embryologic development of the thymus. Ectopic thymic tissue is usually deposited along the pathway from the mandibular angle to the manubrium of the sternum. Most reported cases of an ectopic thymus occurred in children, and cases are less common in adults. We report a 26-year-old woman, who was incidentally found to have 2 neck nodules on the posterior side of the bilateral upper pole of the thyroid gland while undergoing a subtotal thyroidectomy. The left-side neck nodule showed accessory thyroid follicles intermixed with ectopic thymic tissue, and the right-side neck nodule was ectopic parathyroid tissue together with ectopic thymic tissue.

Thymic irradiation and chronic myelogenous leukemia

International Nuclear Information System (INIS)

Shimaoka, K.; Sokal, J.E.

1977-01-01

Two cases of Ph positive chronic myelogenous leukemia with a history of thymic irradiation are presented. Both patients received radiation therapy from low voltage x-ray equipment at two to three months of age. Leukemia developed 18 and 22 years later. Presentation, response to antileukemic therapy, and clinical course did not differ from that of other patients with this disease treated in our department

Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer

International Nuclear Information System (INIS)

Minsky, Bruce D.; Cohen, Alfred M.; Enker, Warren E.; Saltz, Leonard; Guillem, Jose G.; Paty, Philip B.; Kelsen, David P.; Kemeny, Nancy; Ilson, David; Bass, Joanne; Conti, John

1997-01-01

Purpose: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. Methods and Materials: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. Results: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). Conclusion: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response

Photoperiodic modulation of local melatonin synthesis and its role in regulation of thymic homeostasis in Funambulus pennanti.

Science.gov (United States)

Gupta, Sameer; Haldar, Chandana

2016-12-01

The effect of photo-neuroendocrine system on the thymic (immune) functions is mediated by gonadal steroid and the pineal hormone melatonin. The present study explored the effect of photoperiod on the thymic melatonergic system and its role in protection of thymic T-cells from the testosterone induced seasonal oxidative stress and apoptosis. Exposure to long day-length (LD) was noted to decrease local (thymic) melatonin content and induce oxidative stress and apoptosis in the thymus. Increased peripheral level of testosterone upregulated the androgen receptor expression and, consequently reduced proliferation response of the thymocytes. Short day conditions (SD) however, reversed the effect of LD on the thymic physiology. Low level of testosterone was concomitant with diminished nitro-oxidative stress and decreased expression of redox sensitive factors (NF-κB, p53 and Bax/Bcl-2 ratio) in the thymus. SD retarded activation of caspase-3 resulting in procaspase-3 accumulation. Further, in vitro treatment of thymocytes with AR antagonist flutamide impaired the sensitivity of thymocytes to androgen and reversed the deleterious effects of testosterone on the proliferative and apoptotic responses of thymocytes. Therefore, it can be suggested that thymus derived melatonin protects thymic T-cells from testosterone induced seasonal oxidative stress, apoptosis and also acts as a potent paracrine factor for maintenance of redox status to ensure thymocyte survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Cost utility analysis of endoscopic biliary stent in unresectable hilar cholangiocarcinoma: decision analytic modeling approach.

Science.gov (United States)

Sangchan, Apichat; Chaiyakunapruk, Nathorn; Supakankunti, Siripen; Pugkhem, Ake; Mairiang, Pisaln

2014-01-01

Endoscopic biliary drainage using metal and plastic stent in unresectable hilar cholangiocarcinoma (HCA) is widely used but little is known about their cost-effectiveness. This study evaluated the cost-utility of endoscopic metal and plastic stent drainage in unresectable complex, Bismuth type II-IV, HCA patients. Decision analytic model, Markov model, was used to evaluate cost and quality-adjusted life year (QALY) of endoscopic biliary drainage in unresectable HCA. Costs of treatment and utilities of each Markov state were retrieved from hospital charges and unresectable HCA patients from tertiary care hospital in Thailand, respectively. Transition probabilities were derived from international literature. Base case analyses and sensitivity analyses were performed. Under the base-case analysis, metal stent is more effective but more expensive than plastic stent. An incremental cost per additional QALY gained is 192,650 baht (US$ 6,318). From probabilistic sensitivity analysis, at the willingness to pay threshold of one and three times GDP per capita or 158,000 baht (US$ 5,182) and 474,000 baht (US$ 15,546), the probability of metal stent being cost-effective is 26.4% and 99.8%, respectively. Based on the WHO recommendation regarding the cost-effectiveness threshold criteria, endoscopic metal stent drainage is cost-effective compared to plastic stent in unresectable complex HCA.

CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

Science.gov (United States)

2018-05-22

Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer

Utility of Electrocardiography (ECG)-Gated Computed Tomography (CT) for Preoperative Evaluations of Thymic Epithelial Tumors.

Science.gov (United States)

Ozawa, Yoshiyuki; Hara, Masaki; Nakagawa, Motoo; Shibamoto, Yuta

2016-01-01

Preoperative evaluation of invasion to the adjacent organs is important for the thymic epithelial tumors on CT. The purpose of our study was to evaluate the utility of electrocardiography (ECG)-gated CT for assessing thymic epithelial tumors with regard to the motion artifacts produced and the preoperative diagnostic accuracy of the technique. Forty thymic epithelial tumors (36 thymomas and 4 thymic carcinomas) were examined with ECG-gated contrast-enhanced CT using a dual source scanner. The scan delay after the contrast media injection was 30 s for the non-ECG-gated CT and 100 s for the ECG-gated CT. Two radiologists blindly evaluated both the non-ECG-gated and ECG-gated CT images for motion artifacts and determined whether the tumors had invaded adjacent structures (mediastinal fat, superior vena cava, brachiocephalic veins, aorta, pulmonary artery, pericardium, or lungs) on each image. Motion artifacts were evaluated using a 3-grade scale. Surgical and pathological findings were used as a reference standard for tumor invasion. Motion artifacts were significantly reduced for all structures by ECG gating ( p =0.0089 for the lungs and p ECG-gated CT and ECG-gated CT demonstrated 79% and 95% accuracy, respectively, during assessments of pericardial invasion ( p =0.03). ECG-gated CT reduced the severity of motion artifacts and might be useful for preoperative assessment whether thymic epithelial tumors have invaded adjacent structures.

Thymic hyperplasia in a patient with Grave's disease

Directory of Open Access Journals (Sweden)

Hamzaoui Amira A

2012-02-01

Full Text Available Abstract Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.

Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation

International Nuclear Information System (INIS)

Muto, M.; Kubo, E.; Kamisaku, H.; Sado, T.

1990-01-01

Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells

Dabrafenib for Treating Unresectable, Advanced or Metastatic BRAF V600 Mutation-Positive Melanoma: An Evidence Review Group Perspective.

Science.gov (United States)

Fleeman, Nigel; Bagust, Adrian; Beale, Sophie; Boland, Angela; Dickson, Rumona; Dwan, Kerry; Richardson, Marty; Dundar, Yenal; Davis, Helen; Banks, Lindsay

2015-09-01

The National Institute for Health and Care Excellence (NICE) invited GlaxoSmithKline, the manufacturer of dabrafenib, to submit evidence for the clinical and cost effectiveness of dabrafenib for the treatment of unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision in October 2014. The clinical evidence for dabrafenib was derived from an ongoing phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BREAK-3) involving 230 patients randomized 2:1 to receive either dabrafenib or dacarbazine. A significant improvement in median progression-free survival (PFS) but not overall survival (OS) was reported in the dabrafenib arm compared with dacarbazine. Vemurafenib is considered a more appropriate comparator than is dacarbazine. The clinical evidence for vemurafenib was derived from a completed phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BRIM-3) involving 675 patients randomized 1:1 to receive either vemurafenib or dacarbazine. A significant improvement in median PFS and OS was reported in the vemurafenib arm compared with dacarbazine. As there is no direct evidence comparing dabrafenib versus vemurafenib, the company presented an indirect treatment comparison (ITC) that demonstrated no statistical differences between dabrafenib and vemurafenib for PFS or OS. The ERG expressed concerns with the ITC, mainly in relation to the validity of the assumptions underpinning the methodology; the ERG concluded this resulted in findings that are unlikely to be robust or reliable. Dabrafenib and

The cost of unresectable stage III or stage IV melanoma in Italy

Directory of Open Access Journals (Sweden)

Maio Michele

2012-11-01

Full Text Available Abstract Background In recent decades, melanoma incidence has been increasing in European countries; in 2006, there were approximately 60,000 cases leading to 13,000 deaths. Within Europe there is some geographical variation in the incidence of melanoma, with the highest rates reported in Scandinavia (15 cases per 100,000 inhabitants per year and the lowest in the Mediterranean countries (5 to 7 cases per 100,000 inhabitants per year. Methods The present article is based on the information collected in the MELODY study (MELanoma treatment patterns and Outcomes among patients with unresectable stage III or stage IV Disease: a retrospective longitudinal survey. In that study, the medical charts of patients were reviewed to document current treatment patterns and to analyse information on patients, disease characteristics and healthcare resource utilization related to the treatment of advanced melanoma regarding patients who presented with a diagnosis of malignant melanoma (stage I to IV at participating sites between 01 July, 2005 and 30 June, 2006. Results Summarizing, though the length of the follow-up period varies among sample patients, an amount of the yearly cost per patient can be estimated, dividing the average per patient total cost (€ 5.040 by the average follow-up duration (17.5 months and reporting to one year; on these grounds, unresectable stage III or stage IV melanoma in Italy would cost € 3,456 per patient per year.

Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology

Directory of Open Access Journals (Sweden)

Young Il Choi

2013-11-01

Full Text Available An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO mice where mislocalized CD69+ thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1-/- genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1flox/flox mice crossed to pLck-Cre, pKeratin14-Cre or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CKO lines involving thymocytes (D1ThyCKO, thymic epithelium (D1EpCKO and thymic endothelium (D1EnCKO, respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components.

Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies

Energy Technology Data Exchange (ETDEWEB)

Burgmans, Mark C., E-mail: m.c.burgmans@lumc.nl [Leiden University Medical Centre, Department of Radiology (Netherlands); Leede, Eleonora M. de, E-mail: e.m.de-leede@lumc.nl [Leiden University Medical Centre, Department of Surgery (Netherlands); Martini, Christian H., E-mail: c.h.martini@lumc.nl [Leiden University Medical Centre, Department of Anesthesiology (Netherlands); Kapiteijn, Ellen, E-mail: h.w.kapiteijn@lumc.nl [Leiden University Medical Centre, Department of Medical Oncology (Netherlands); Vahrmeijer, Alexander L., E-mail: a.l.vahrmeijer@lumc.nl [Leiden University Medical Centre, Department of Surgery (Netherlands); Erkel, Arian R. van, E-mail: a.r.van-erkel@lumc.nl [Leiden University Medical Centre, Department of Radiology (Netherlands)

2016-06-15

Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest and the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.

Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies

International Nuclear Information System (INIS)

Burgmans, Mark C.; Leede, Eleonora M. de; Martini, Christian H.; Kapiteijn, Ellen; Vahrmeijer, Alexander L.; Erkel, Arian R. van

2016-01-01

Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest and the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.

Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

Science.gov (United States)

Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

2015-06-01

To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

Effect of granulocyte colony-stimulating factor on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation

International Nuclear Information System (INIS)

Zhao Hongxia; Guo Mei; Sun Xuedong; Ai Huisheng

2011-01-01

Objective: To investigate the effects of recombinant human granulocyte colony stimulating factor (G-CSF) on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation. Methods: Female BALB/c mice were irradiated with a 6.0 Gy of γ-ray total-body irradiation and then randomly divided into GCSF group and control group. For mice in the GCSF group, recombinant human G-CSF 100 μg · kg -1 · d -1 was injected subcutaneously once daily for 14 continuous days and mice in the control group were given the same volume of phosphate buffered solution (PBS). At 7, 14, 21 and 28 days later, mice were killed and thymus mononuclear cell suspension were analyzed by flow cytometry for the percentage of the four stages of thymic CD4 - CD8 - double negative cells (DN1-4) and the CD4 + CD8 + double positive ( CD4 + CD8 + DP), CD4 + CD8 - single positive (CD4 + SP), CD4 - CD8 + single positive cells (CD8 + SP).Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTRECs) of the thymic cells of 30 and 60 d after irradiation. Results: The percentage of thymic DN1 cells in GCSF group was significantly higher than that of the control group 7 d after irradiation (t=9.59, P<0.05). 21 d later, the proportion of thymic DN3 and DN4 cells were higher than those of the control group (t=16.37, 7.6, P<0.05). The percentage of thymic CD4 + CD8 + DP cells decreased 7 d after irradiation,increased at 14 d, decreased again at 21 days,and then got a permanent recover. The percentage of thymic CD4 + CD8 + DP cells in the GCSF group recovered to normal and was significantly higher than that of the control group 28 days after irradiation (t=12.22, P<0.05). The percentage of thymic CD8 + SP cells of the GCSF group was significantly higher than that of the control group 21 d after irradiation (t=3.77, P<0.05), while G-CSF had no obvious influence on the percentage of the thymic CD4 + SP cells. The sjTRECs copies in the

S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

Science.gov (United States)

Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

2014-05-01

Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

Multimodal treatment for unresectable pancreatic cancer

International Nuclear Information System (INIS)

Katayama, Kanji; Iida, Atsushi; Fujita, Takashi; Kobayashi, Taizo; Shinmoto, Syuichi; Hirose, Kazuo; Yamaguchi, Akio; Yoshida, Masanori

1998-01-01

In order to improve in prognosis and quality of life (QOL), the multimodal treatment for unresectable pancreatic cancers were performed. Bypass surgery was carried out for unresectable pancreatic cancer with intraoperative irradiation (IOR). After surgery, patients were treated with the combination of CDDP (25 mg) and MMC (4 mg) administration, intravenously continuous injection of 5-FU (250 mg for 24 hours), external radiation by the high voltage X-ray (1.5 Gy per irradiation, 4 times a week, and during hyperthermia 3 Gy per irradiation) and hyperthermia using the Thermotron RF-8 warmer. Six out of 13 patients received hyperthermia at over 40degC, were obtained PR, and their survival periods were 22, 21, 19, 18, 11 and 8 months and they could return to work. For all patients with pain, the symptom was abolished or reduced. The survival periods in cases of the multimodal treatment were longer than those of only bypass-surgery or of the resective cases with the curability C. The multimodal treatment combined with radiation, hyperthermia and surgery is more useful for the removal of pain and the improvement of QOL, and also expected the improvement of the prognosis than pancreatectomy. And hyperthermia has an important role on the effect of this treatment. (K.H.)

Multimodal treatment for unresectable pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Katayama, Kanji; Iida, Atsushi; Fujita, Takashi; Kobayashi, Taizo; Shinmoto, Syuichi; Hirose, Kazuo; Yamaguchi, Akio; Yoshida, Masanori [Fukui Medical School, Matsuoka (Japan)

1998-07-01

In order to improve in prognosis and quality of life (QOL), the multimodal treatment for unresectable pancreatic cancers were performed. Bypass surgery was carried out for unresectable pancreatic cancer with intraoperative irradiation (IOR). After surgery, patients were treated with the combination of CDDP (25 mg) and MMC (4 mg) administration, intravenously continuous injection of 5-FU (250 mg for 24 hours), external radiation by the high voltage X-ray (1.5 Gy per irradiation, 4 times a week, and during hyperthermia 3 Gy per irradiation) and hyperthermia using the Thermotron RF-8 warmer. Six out of 13 patients received hyperthermia at over 40degC, were obtained PR, and their survival periods were 22, 21, 19, 18, 11 and 8 months and they could return to work. For all patients with pain, the symptom was abolished or reduced. The survival periods in cases of the multimodal treatment were longer than those of only bypass-surgery or of the resective cases with the curability C. The multimodal treatment combined with radiation, hyperthermia and surgery is more useful for the removal of pain and the improvement of QOL, and also expected the improvement of the prognosis than pancreatectomy. And hyperthermia has an important role on the effect of this treatment. (K.H.)

Thymic masses: A radiological review | Mittal | SA Journal of Radiology

African Journals Online (AJOL)

Abstract. Various thymic masses and their normal variations have different pathological and management consequences. Radiologists and clinicians should be aware of these entities so that appropriate and timely treatment can be given.

New tapered metallic stent for unresectable malignant hilar bile duct obstruction.

Science.gov (United States)

Sakai, Yuji; Tsuyuguchi, Toshio; Nishikawa, Takao; Sugiyama, Harutoshi; Sasaki, Reina; Sakamoto, Dai; Watanabe, Yuto; Nakamura, Masato; Yasui, Shin; Mikata, Rintaro; Yokosuka, Osamu

2015-10-16

To examine the usefulness of a new tapered metallic stent (MS) in patients with unresectable malignant hilar bile duct obstruction. This new tapered MS was placed in 11 patients with Bismuth II or severer unresectable malignant hilar bile duct obstruction, as a prospective study. The subjects were six patients with bile duct carcinoma, three with gallbladder cancer, and two with metastatic bile duct obstruction. Stenosis morphology was Bismuth II: 7, IIIa: 3, and IV: 1. UMIN Clinical Trial Registry (UMIN000004758). MS placement was 100% (11/11) successful. There were no procedural accidents. The mean patency period was 208.401 d, the median survival period was 142.000 d, and the mean survival period was 193.273 d. Occlusion rate was 36.4% (4/11); the causes of occlusion were ingrowth and overgrowth in 2 patients each, 18.2%, respectively. Patients with occlusion underwent endoscopic treatment one more time and all were treatable. The tapered MS proved useful in patients with unresectable malignant hilar bile duct obstruction because it provided a long patency period, enabled re-treatment by re-intervention, and no procedural accidents occurred.

Abnormalities of thymic stroma may contribute to immune dysregulation in murine models of leaky severe combined immunodeficiency

Directory of Open Access Journals (Sweden)

Francesca eRucci

2011-05-01

Full Text Available Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky SCID, carrying hypomorphic mutations in Rag1 and Lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs. While the ability of mTECs to express Aire is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens (TSAs is severely reduced. Similarly, the ability of CD4+ T cells to differentiate into Foxp3+ natural regulatory T cells is preserved in Rag1 and Lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation.

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

International Nuclear Information System (INIS)

Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

2013-01-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

Energy Technology Data Exchange (ETDEWEB)

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

FOXN1: a master regulator gene of thymic epithelial development programme

Directory of Open Access Journals (Sweden)

Rosa eRomano

2013-07-01

Full Text Available T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs drive T cell differentiation, education and selection processes, while the thymocyte-dependent signals allow TECs to maturate and provide an appropriate thymic microenvironment. Alterations in genes implicated in thymus organogenesis, including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1 and Six1, affect this well-orchestrated process, leading to disruption of thymic architecture. Of note, in both human and mice, the primordial TECs are yet unable to fully support T cell development and only after the transcriptional activation of the Forkhead-box n1 (FOXN1 gene in the thymic epithelium this essential function is acquired. FOXN1 is a master regulator in the TEC lineage specification in that it down-stream promotes transcription of genes, which, in turn, regulate TECs differentiation. In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC homeostasis in the postnatal thymus. An inborn null mutation in FOXN1 leads to Nude/SCID phenotype in mouse, rat and humans. In Foxn1-/- nude animals, initial formation of the primordial organ is arrested and the primordium is not colonized by hematopoietic precursors, causing a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail dystrophy and a severe T cell immunodeficiency, inherited as an autosomal recessive disorder. Aim of this review is to summarize all the scientific information so far available to better characterize the pivotal role of the master regulator FOXN1 transcription factor in the TEC lineage specifications and functionality.

Different mechanisms for the resistance of C3H and STS strain mice to the development of thymic lymphomas following fractionated whole-body irradiation

International Nuclear Information System (INIS)

Aizawa, Shiro; Kamisaku, Hitoko

1999-01-01

B10 strain mice are extremely susceptible for induction of thymic lymphomas by fractionated whole-body irradiation (FI), whereas C3H and STS mice are fairly resistant. In the present study, we constructed radiation bone marrow chimeras in the reciprocal donor-host combinations of susceptible and resistant mice with use of Thy1 markers that allow to determine genetic origins of donor- and host-type thymocytes, and then to analyze the influence of host/thymic environment on the strain-dependent susceptibility to thymic lymphomagenesis. B10.Thy1.1→C3H, B10.Thy1.1→STS as well as B10.Thy1.1→B10 bone marrow chimeras manifested a high incidence of thymic lymphomas after FI-treatment, whereas C3H. Thy1.1→B10 and STS→B10 as well as C3H→C3H and STS→STS chimeras manifested a low incidence of thymic lymphoma. Furthermore, FI-treatment of [B10.Thy1.1+C3H]→B10 mixed chimeras resulted in the generation of similar numbers of thymic lymphomas of B10 and C3H origins, whereas FI-treatment of [B10.Thy1.1+STS]→B10 mixed chimeras preferentially induced thymic lymphomas of B10 origin. These results indicated that host environments of C3H and STS resistant mice are not inhibitory for the development of thymic lymphomas, genetic factors responsible for the strain-dependent susceptibility and/or resistance to FI-induced lymphomagenesis exert their effects entirely on bone-marrow derived cells, and the resistance of STS mice to FI-induced thymic lymphomagenesis is an intrinsic property of thymocytes as the targets of thymic lymphoma induction, whereas bone marrow-derived thymic stroma cells seem to play a significant role in the resistance of C3H mice for the induction of thymic lymphomas. (author)

Laparoscopic stomach-partitioning gastrojejunostomy with reduced-port techniques for unresectable distal gastric cancer.

Science.gov (United States)

Hirahara, Noriyuki; Matsubara, Takeshi; Hyakudomi, Ryoji; Hari, Yoko; Fujii, Yusuke; Tajima, Yoshitsugu

2014-03-01

The improvement of quality of life is of great importance in managing patients with far-advanced gastric cancer. We report a new cure and less invasive method of creating a stomach-partitioning gastrojejunostomy in reduced-port laparoscopic surgery for unresectable gastric cancers with gastric outlet obstruction. A 2.5-cm vertical intraumbilical incision was made, and EZ Access (Hakko Co., Ltd., Tokyo, Japan) was placed. After pneumoperitoneum was created, an additional 5-mm trocar was inserted in the right upper abdomen. A gastrojejunostomy was performed in the form of an antiperistaltic side-to-side anastomosis, in which the jejunal loop was elevated in the antecolic route and anastomosed to the greater curvature of the stomach using an endoscopic linear stapler. The jejunal loop together with the stomach was dissected with additional linear staplers just proximal to the common entry hole so that a functional end-to-end gastrojejunostomy was completed. At the same time, the stomach was partitioned using a linear stapler to leave a 2-cm-wide lumen in the lesser curvature. Subsequently, jejunojejunostomy was performed 30 cm distal to the gastrojejunostomy, and the stomach-partitioning gastrojejunostomy resembling Roux-en Y anastomosis was completed. All patients resumed oral intake on the day of operation. Neither anastomotic leakage nor anastomotic stricture was observed. Our less invasive palliative operation offers the utmost priority to improve quality of life for patients with unresectable gastric cancer.

CT-guided high-dose-rate brachytherapy of unresectable hepatocellular carcinoma

International Nuclear Information System (INIS)

Collettini, Federico; Schreiber, Nadja; Schnapauff, Dirk; Denecke, Timm; Hamm, Bernd; Gebauer, Bernhard; Wust, Peter; Schott, Eckart

2015-01-01

The purpose of the present study was to evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) in patients with unresectable hepatocellular carcinoma (HCC). Over a 6-year period, 98 patients with 212 unresectable HCC underwent CT-HDRBT applying a 192 Ir source at our institution. Magnetic resonance imaging (MRI) follow-up was performed 6 weeks after the intervention and then every 3 months. The primary endpoint was local tumor control (LTC); secondary endpoints included progression-free survival (PFS) and overall survival (OS). Patients were available for MRI evaluation for a mean follow-up of 23.1 months (range 4-64 months; median 20 months). Mean tumor diameter was 5 cm (range 1.8-12 cm). Eighteen of 212 (8.5 %) tumors showed local progression after a mean LTC of 21.1 months. In all, 67 patients (68.4 %) experienced distant tumor progression. The mean PFS was 15.2 months. Forty-six patients died during the follow-up period. Median OS was 29.2 months. Actuarial 1-, 2-, and 3-year OS rates were 80, 62, and 46 %, respectively. CT-HDRBT is an effective therapy to attain local tumor control in patients with unresectable HCC. Prospective randomized studies comparing CT-HDRBT with the standard treatments like Radiofrequency ablation (RFA) and chemoembolization (TACE) are mandatory. (orig.) [de

Can a Proper T-Cell Development Occur in an Altered Thymic Epithelium? Lessons From EphB-Deficient Thymi

Directory of Open Access Journals (Sweden)

Juan José Muñoz

2018-04-01

Full Text Available For a long time, the effects of distinct Eph tyrosine kinase receptors and their ligands, ephrins on the structure, immunophenotype, and development of thymus and their main cell components, thymocytes (T and thymic epithelial cells (TECs, have been studied. In recent years, the thymic phenotype of mutant mice deficient in several Ephs and ephrins B has been determined. Remarkably, thymic stroma in these animals exhibits important defects that appear early in ontogeny but little alterations in the proportions of distinct lymphoid cell populations. In the present manuscript, we summarize and extend these results discussing possible mechanisms governing phenotypical and functional thymocyte maturation in an absence of the critical T–TEC interactions, concluding that some signaling mediated by key molecules, such as MHCII, CD80, β5t, Aire, etc. could be sufficient to enable a proper maturation of thymocytes, independently of morphological alterations affecting thymic epithelium.

A stromal myoid cell line provokes thymic erythropoiesis between ...

African Journals Online (AJOL)

Background: The thymus provides an optimal cellular and humoral microenvironment for cell line committed differentiation of haematopoietic stem cells. The immigration process requires the secretion of at least one peptide called thymotaxine by cells of the reticulo-epithelial (RE) network of the thymic stromal cellular ...

The study of combination therapy for arterial infusion chemotherapy and radiation therapy in unresectable gallbladder cancer

International Nuclear Information System (INIS)

Goto, Takuma; Saito, Hiroya; Yanagawa, Nobuyuki; Fujinaga, Akihiro; Saito, Yoshinori

2013-01-01

In this study, we investigated an effective strategy of treatment for unresectable gallbladder cancer (GBC) by the retrospective analysis of prognostic factors and anti-tumor therapies, especially combination therapy of arterial infusion chemotherapy and radiation therapy (AI+PT). Forty-three patients with unresectable GBC were enrolled, and prognostic factors were investigated by multivariate analysis using a proportional hazard model. In addition, we examined the indication and after-therapy by analyzing the each factor cumulative survival rates and anti-tumor effect about the AI + RT group (n=24). AI + RT and the responders to the first-line therapy were significant prognostic factors. In AI + RT group, median survival time, progression-free survival and the 1-year survival rate, the response and disease control rates was 15.5 months, 7.1 months, 62.5%. 54.2% and 95.8%, respectively; which suggested prolonged survival and high anti-tumor effect. Cumulative survival rate was significantly shorter in cases with distant metastasis except liver metastases, and has been tendency to extend in the group who underwent systemic chemotherapy as after-therapy. The treatment strategy, using the Al + RT as first-line with the systemic chemotherapy as after-therapy, suggested contribute to the prolonged survival in locally advanced and liver metastases cases of GBC. (author)

Reactive thymic hyperplasia following treatment of ACTH-producing tumors

International Nuclear Information System (INIS)

Schmidt, S.; Klose, K.J.; Iwinska-Zelder, J.; Frank, M.; Ehlenz, K.; Kisker, O.

1997-01-01

Surgical or conservative treatment of ACTH-producing tumors results in acute drop of the previously excessively high cortisol levels. The following associated pathophysiological changes also occur in the organism's recovery from stress, such as trauma, operation or chemotherapy of tumors. Both cases result in a regeneration of the immune system, which might even be exalted. The corresponding radiographic feature is the 'rebound' enlargement of the thymus occuring about six months after remission of hypercortisolism. Histological examination reveals benign thymus hyperplasia. Especially in cases of still unkown primary tumor the apperance of this anterior mediastinal mass can lead to misdiagnosis. We present the cases of two patients with diffuse thymic hyperplasia following surgical and medical correction of hypercortisolism. One patient suffered from classic Cushing's disease responding to transsphenoidal resection of an ACTH-secreting pituitary microadenoma. Six monsths later CT of the chest incidentally demonstrated an anterior mediastinal mass known as thymic hyperplasia. The second patient presented with an ectopic, still unknown source of ACTH-production. (orig./AJ) [de

Phase II trial of upfront bevacizumab and temozolomide for unresectable or multifocal glioblastoma

International Nuclear Information System (INIS)

Lou, Emil; Peters, Katherine B; Sumrall, Ashley L; Desjardins, Annick; Reardon, David A; Lipp, Eric S; Herndon, James E II; Coan, April; Bailey, Leighann; Turner, Scott; Friedman, Henry S; Vredenburgh, James J

2013-01-01

Patients with unresectable glioblastomas have a poor prognosis, with median survival of 6–10 months. We conducted a phase II trial of upfront 5-day temozolomide (TMZ) and bevacizumab (BV) in patients with newly diagnosed unresectable or multifocal glioblastoma. Patients received up to four cycles of TMZ at 200 mg/m 2 on days 1–5, and BV at 10 mg/kg on days 1 and 15 of a 28-day cycle. Brain magnetic resonance imaging (MRI) was performed monthly. Therapy was continued as long as there was no tumor progression, grade 4 nonhematologic toxicity, or recurrent grade 4 hematologic toxicity after dose reduction. The primary end point was best tumor response as measured on MRI. Forty-one patients were accrued over 12 months; 39 had a full set of MRI scans available for evaluation. Assessment for best radiographic responses was as follows: partial responses in 24.4%, stable disease in 68.3%, and progressive disease in 2.4%. Treatment-related toxicities included seven grade 4 toxicities and one grade 5 toxicity (myocardial infarction). From this study, it was concluded that an upfront regimen of TMZ and BV for unresectable glioblastoma was well tolerated and provided a significant level of disease stabilization. Therapeutic toxicities were consistent with those seen in the adjuvant setting using these agents. The upfront approach to treatment of glioblastoma in the unresectable population warrants further investigation in randomized controlled phase III trials

Association of murine lupus and thymic full-length endogenous retroviral expression maps to a bone marrow stem cell

International Nuclear Information System (INIS)

Krieg, A.M.; Gourley, M.F.; Steinberg, A.D.

1991-01-01

Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymic epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells

DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.

Directory of Open Access Journals (Sweden)

Masako Osada

2010-02-01

Full Text Available Thymic epithelial cell (TEC microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus.Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+ Foxn1(+ and Aire(+ TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments.Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic

Effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue

Directory of Open Access Journals (Sweden)

Lei Liu

2016-11-01

Full Text Available Objective: To study the effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue. Methods: A total of 144 patients with locally advanced gastric cancer receiving surgical resection after neoadjuvant chemotherapy in our hospital between May 2012 and August 2015 were selected and randomly divided into experimental group who received preoperative oral S-1 combined with regional intra-arterial chemotherapy and control group who received preoperative intravenous systemic chemotherapy. The levels of serum tumor markers were determined after chemotherapy, and the expression levels of tumor suppressor genes and cell cycle-related molecules in tumor tissue were determined after surgical resection. Results: After neoadjuvant chemotherapy, the serum G-17, TK-1, CEA, CA19-9, CA12-5, CA72-4 and CK, CK-MB, ALT, AST levels of experimental group were significantly lower than those of control group; after surgical resection, the p16, p27, PTEN and TXNIP mRNA levels in tumor tissue of experimental group were significantly higher than those of control group while CyclinB2, CyclinD1, CyclinE, CDK1 and CDK2 mRNA levels were significantly lower than those of control group. Conclusions: Preoperative oral S-1 combined with regional intra-arterial chemotherapy can more effectively kill gastric cancer cells, reduce tumor load, inhibit cell cycle and promote cell apoptosis.

A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing's syndrome.

Science.gov (United States)

Trott, M J; Farah, G; Stokes, V J; Wang, L M; Grossman, A B

2016-01-01

We present a case of a young female patient with a rare cause of relapsing and remitting Cushing's syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing's syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms 'relapsing and remitting' in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing's syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking. Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing's syndromeThere is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohortAn exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populationsThe relapsing and remitting course of our patient's symptoms is noteworthy, given the paucity of this finding among other published cases.

Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H., E-mail: ccrane@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2013-03-01

Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a

A case of congenital Langerhans cell histiocytosis with skin and thymic lesions: Exploring the prognostic value of thymus involvement

Directory of Open Access Journals (Sweden)

M.M. Escudero-Góngora

2016-10-01

Full Text Available Thymus evaluation is not included in the guidelines of the Histiocyte Society, so its prevalence, management and prognosis are not well established. We present a newborn with self-healing cutaneous LCH and thymic involvement that was evaluated with a thoracic ultrasound. With the current evidence we are unable to predict the prognosis of the thymus association in neonatal LCH. We suggest that performing thymic ultrasound study, which is a non-invasive technique, would allow us to know the incidence of thymic involvement and its role on prognosis.

Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells

Science.gov (United States)

Sojka, Dorothy K; Plougastel-Douglas, Beatrice; Yang, Liping; Pak-Wittel, Melissa A; Artyomov, Maxim N; Ivanova, Yulia; Zhong, Chao; Chase, Julie M; Rothman, Paul B; Yu, Jenny; Riley, Joan K; Zhu, Jinfang; Tian, Zhigang; Yokoyama, Wayne M

2014-01-01

Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. DOI: http://dx.doi.org/10.7554/eLife.01659.001 PMID:24714492

A pediatric case of life-threatening airway obstruction caused by a cervicomediastinal thymic cyst

Energy Technology Data Exchange (ETDEWEB)

Komura, Makoto; Kanamori, Yutaka; Sugiyama, Masahiko; Iwanaka, Tadashi [University of Tokyo Hospital, Department of Pediatric Surgery, Tokyo (Japan); Fukushima, Noriyoshi [University of Tokyo Hospital, Department of Pathology, Tokyo (Japan)

2010-09-15

Most patients with thymic cysts complain of a slowly enlarging, asymptomatic cervical mass. Only 6-10% suffer dysphagia, dyspnoea, stridor, cervical pain or vocal paralysis. In some rare cases sudden onset of severe dyspnoea or asphyxia is the first symptom, especially in neonates and small infants. We report a unique case of a 20-month-old child, who required emergency tracheal intubation due to asphyxia. Cervicomediastinal thymic cyst might need to be included in causes of life-threatening airway obstruction in young children. (orig.)

Expression of tyrosine kinase gene in mouse thymic stromal cells

NARCIS (Netherlands)

Rinke de Wit, T. F.; Izon, D. J.; Revilla, C.; Oosterwegel, M.; Bakker, A. Q.; van Ewijk, W.; Kruisbeek, A. M.

1996-01-01

Amongst the most important signal transduction molecules involved in regulating growth and differentiation are the protein tyrosine kinases (PTK). Since T cell development is a consequence of interactions between thymic stromal cells (TSC) and thymocytes, identification of the PTK in both

Thymic size at birth in preterm infants with severe respiratory ...

African Journals Online (AJOL)

To determine whether the thymic size in preterm infants with severe respiratory distress syndrome (RDS) can be used to predict ... chorio-amnionitis is associated with a small thymus at birth.4,7. In those ..... Acta Paediatr 2000; 89: 975-978. 6.

The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma

Energy Technology Data Exchange (ETDEWEB)

Janowski, M [Centre d' Etude de l' Energie Nucleaire, Mol (Belgium); Cox, R [Medical Research Council, Harwell (UK). Radiobiological Research Unit; Strauss, P G [GSF, Neuherberg (Germany, F.R.). Abt. fuer Molekulare Zellpathologie

1990-04-01

In mice, external X- or {gamma}-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking {alpha}-emitters may induce osteosarcomas, and to a lesser extent acute myeloid leukaemia. The paper reviews briefly some experimental data in respect to molecular mechanisms underlying these radio-carcinogenic processes. Thymic lymphomagenesis proceeds by an indirect mechanism in which recombinant proviruses could be involved. Myeloid leukaemogenesis is characterized by a very early putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumors often contain somatically acquired proviruses. (UK).

Alteration of T cell function in healthy persons with a history of thymic x irradiation

International Nuclear Information System (INIS)

Rieger, C.H.L.; Kraft, S.C.; Rothberg, R.M.

1975-01-01

The possible late effects of x irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytohemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptokinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis

Alteration of T cell function in healthy persons with a history of thymic x irradiation

Energy Technology Data Exchange (ETDEWEB)

Rieger, C.H.L.; Kraft, S.C.; Rothberg, R.M.

1975-10-01

The possible late effects of x irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytohemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptokinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis.

Unresectable Carcinoma of the Paranasal Sinuses: Outcomes and Toxicities

International Nuclear Information System (INIS)

Hoppe, Bradford S.; Nelson, Carl J.; Gomez, Daniel R.; Stegman, Lauren D.; Wu, Abraham J.; Wolden, Suzanne L.; Pfister, David G.; Zelefsky, Michael J.; Shah, Jatin P.; Kraus, Dennis H.; Lee, Nancy Y.

2008-01-01

Purpose: To evaluate long-term outcomes and toxicity in patients with unresectable paranasal sinus carcinoma treated with radiotherapy, with or without chemotherapy. Methods and Materials: Between January 1990 and December 2006, 39 patients with unresectable Stage IVB paranasal sinus carcinoma were treated definitively with chemotherapy plus radiotherapy (n = 35, 90%) or with radiotherapy alone (n = 4, 10%). Patients were treated with three-dimensional conformal radiotherapy (n = 18, 46%), intensity-modulated radiotherapy (n = 12, 31%), or conventional radiotherapy (n = 9, 23%) to a median treatment dose of 70 Gy. Most patients received concurrent platinum-based chemotherapy (n = 32, 82%) and/or concomitant boost radiotherapy (n = 29, 74%). Results: With a median follow-up of 90 months, the 5-year local progression-free survival, regional progression-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 21%, 61%, 51%, 14%, and 15%, respectively. Patients primarily experienced local relapse (n = 25, 64%), mostly within the irradiated field (n = 22). Nine patients developed neck relapses; however none of the 4 patients receiving elective neck irradiation had a nodal relapse. In 13 patients acute Grade 3 mucositis developed. Severe late toxicities occurred in 2 patients with radionecrosis and 1 patient with unilateral blindness 7 years after intensity-modulated radiation therapy (77 Gy to the optic nerve). The only significant factor for improved local progression-free survival and overall survival was a biologically equivalent dose of radiation ≥65 Gy. Conclusions: Treatment outcomes for unresectable paranasal sinus carcinoma are poor, and combined-modality treatment is needed that is both more effective and associated with less morbidity. The addition of elective neck irradiation may improve regional control

Spleen and thymic sonography as estimator of the immune response in children with repeated infections

International Nuclear Information System (INIS)

Rabaza, Jesus; Fundora, Hermes; Rodriguez, Alexis; Hernandez, Maria de los Angeles

2010-01-01

The spleen is a secondary lymphoid organ. The spleen has many functions: IgM class antibody production and phagocytosis of encapsulated bacteria. We propose to measure the dimensions of the spleen in children with repeated infections, in order to describe them as a diagnosis marker and to explore the probable correlation between the thymic characteristics and the dimensions of the spleen. We study 81 patients that attended the consultation of Immunology from Aballi hospital with repeated infections and they were from 8 months to 9 years old. Children with nutritional value up to the third percentile and those taking steroids 45 days before the study were excluded. We measured the thymic and splenic areas by mediastinal and abdominal echography. The length, the splenic index and the weight are less in patients with repeated infections. These data were significant in 12 to 23 month of age group. The length and the splenic index were less in patients with depletion of thymic area. The sonographic evaluation of the spleen is very important in patients from 1 to 2 years old and in patients with thymic depletion, because they are on the age of vaccine administration according to the Cuban schedule and having affected a main organ for immune response might be a reason for them to show a deficient response and need special schedules

Direct analysis of thymic function in children with Down's syndrome

Directory of Open Access Journals (Sweden)

Meschiari Liviana

2005-02-01

Full Text Available Abstract Background Down's syndrome (DS is characterized by several immunological defects, especially regarding T cell compartment. DS is considered the best example of accelerated ageing in humans. Direct observations of the thymus have shown that in DS this organ undergoes severe histological and morphological changes. However, no data on its capacity to generate T cells are present in the literature. Here, using a new technology based upon real time PCR, we have investigated the capacity of the thymus to produce and release newly generated T lymphocytes (the so called "recent thymic emigrants", RTE in children with DS. Methods We studied 8 children affected by DS, aged 2–7 years, compared with 8 age- and sex-matched healthy controls. Flow cytometry was used to determine different lymphocytes subsets. Real time PCR with the Taqman system was used to quantify the amount of RTE, i.e. peripheral blood lymphocytes that express the T cell receptor rearrangement excision circles (TREC. Results In comparison with control children, those with DS had a significant lower number of TREC+ peripheral blood cells. Moreover, in DS children but not in controls, a strong negative correlation between age and the levels of TREC+ cells was found. Conclusions The direct measure of thymic output indicates that the impairment of the organ results in a reduced production of newly generated T cells. This observation could suggest that cytokines able to modulate thymic function, such as interleukins, could be useful to improve the functionality of the organ and to treat the immunodeficiency present in DS subjects.

Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial.

Science.gov (United States)

Grignani, Giovanni; Palmerini, Emanuela; Ferraresi, Virginia; D'Ambrosio, Lorenzo; Bertulli, Rossella; Asaftei, Sebastian Dorin; Tamburini, Angela; Pignochino, Ymera; Sangiolo, Dario; Marchesi, Emanuela; Capozzi, Federica; Biagini, Roberto; Gambarotti, Marco; Fagioli, Franca; Casali, Paolo Giovanni; Picci, Piero; Ferrari, Stefano; Aglietta, Massimo

2015-01-01

Results of previous study showed promising but short-lived activity of sorafenib in the treatment of patients with unresectable advanced and metastatic osteosarcoma. This treatment failure has been attributed to the mTOR pathway and might therefore be overcome with the addition of mTOR inhibitors. We aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable high-grade osteosarcoma progressing after standard treatment. We did this non-randomised phase 2 trial in three Italian Sarcoma Group centres. We enrolled adults (≥18 years) with relapsed or unresectable osteosarcoma progressing after standard treatment (methotrexate, cisplatin, and doxorubicin, with or without ifosfamide). Patients received 800 mg sorafenib plus 5 mg everolimus once a day until disease progression or unacceptable toxic effects. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01804374. We enrolled 38 patients between June 16, 2011, and June 4, 2013. 17 (45%; 95% CI 28-61) of 38 patients were progression free at 6 months. Toxic effects led to dose reductions, or short interruptions, or both in 25 (66%) of 38 patients and permanent discontinuation for two (5%) patients. The most common grade 3-4 adverse events were lymphopenia and hypophosphataemia each in six (16%) patients, hand and foot syndrome in five (13%), thrombocytopenia in four (11%), and fatigue, oral mucositis, diarrhoea, and anaemia each in two (5%). One patient (3%) had a grade 3 pneumothorax that required trans-thoracic drainage, and that recurred at the time of disease progression. This was reported as a serious adverse event related to the study drugs in both instances. No other serious adverse events were reported during the trial. There were no treatment-related deaths. Although the combination of sorafenib and everolimus showed activity as a further-line treatment

A False Positive I-131 Metastatic Survey Caused by Radioactive Iodine Uptake by a Benign Thymic Cyst

Directory of Open Access Journals (Sweden)

Avneet K. Singh

2017-01-01

Full Text Available Thyroid carcinoma is the most common endocrine malignancy in the United States with increasing incidence and diagnosis but stable mortality. Differentiated thyroid cancer rarely presents with distant metastases and is associated with a low risk of morbidity and mortality. Despite this, current protocols recommend remnant ablation with radioactive iodine and evaluation for local and distant metastasis in some patients with higher risk disease. There are several case reports of false positive results of metastatic surveys that are either normal physiologic variants or other pathological findings. Most false positive findings are associated with tissue that has physiologic increased uptake of I-131, such as breast tissue or lung tissue; pathological findings such as thymic cysts are also known to have increased uptake. Our case describes a rare finding of a thymic cyst found on a false positive I-131 metastatic survey. The patient was taken for surgical excision and the final pathology was a benign thymic cyst. Given that pulmonary metastases of differentiated thyroid cancer are rare, thymic cysts, though also rare, must be part of the differential diagnosis for false positive findings on an I-131 survey.

Clinical results of definitive-dose (50 Gy/25 fractions) preoperative chemoradiotherapy for unresectable esophageal cancer

International Nuclear Information System (INIS)

Ishikawa, Kazuki; Nakamatsu, Kiyoshi; Shiraishi, Osamu; Yasuda, Takushi; Nishimura, Yasumasa

2015-01-01

The clinical results of definitive-dose preoperative chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal cancer were analyzed. Inclusion criteria were unresectable esophageal squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined concurrently with two courses of FP therapy (CDDP 70 mg/m 2 + 5-FU 700 mg/m 2 /d x 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were enrolled between 2008 and 2011. The clinical stages according to the 7th edition of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3, 3/25/1/1. All 30 patients completed RT of 50 Gy/ 25 fractions. Initial tumor responses were 21 patients with resectable disease, 7 with unresectable disease, and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60%) of the 30 patients. Pathological complete response was obtained in five (28%) patients. There were two patients with hospitalization death after surgery (11%). Six of the 7 patients who still had unresectable disease were treated with 1-3 courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery showed long-term survival. The 3-year locoregional control rate and the 3-year overall survival rate for the 30 patients were 70 and 49%, respectively. Definitive-dose preoperative CRT was feasible, and is a promising treatment strategy for unresectable esophageal cancer. (author)

Value of intraoperative radiotherapy in locally advanced rectal cancer

NARCIS (Netherlands)

Ferenschild, Floris T. J.; Vermaas, Maarten; Nuyttens, Joost J. M. E.; Graveland, Wilfried J.; Marinelli, Andreas W. K. S.; van der Sijp, Joost R.; Wiggers, Theo; Verhoef, Cornelis; Eggermont, Alexander M. M.; de Wilt, Johannes H. W.

PURPOSE: This study was designed to analyze the results of a multimodality treatment using preoperative radiotherapy, followed by surgery and intraoperative radiotherapy in patients with primary locally advanced rectal cancer. METHODS: Between 1987 and 2002, 123 patients with initial unresectable

Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting.

Science.gov (United States)

Imbimbo, Martina; Maury, Jean-Michel; Garassino, Marina; Girard, Nicolas

2018-02-02

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Models of Aire-dependent gene regulation for thymic negative selection

Directory of Open Access Journals (Sweden)

Dina eDanso-Abeam

2011-05-01

Full Text Available Mutations in the Autoimmune Regulator (AIRE gene lead to Autoimmune Polyendocrinopathy Syndrome type 1 (APS1, characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, with AIRE driving the expression of tissue restricted antigens (TRAs in the epithelial cells of the thymic medulla. This TRA expression results in effective negative selection of TRA-reactive thymocytes, preventing autoimmune disease. At the molecular level, the mechanism by which AIRE initiates TRA expression in the thymic medulla remains unclear. Multiple different models for the molecular mechanism have been proposed, ranging from classical transcriptional activity, to random induction of gene expression, to epigenetic tag recognition effect, to altered cell biology. In this review, we evaluate each of these models and discuss their relative strengths and weaknesses.

Effects of marrow grafting on preleukemia cells and thymic nurse cells in C57BL/Ka mice after a leukemogenic split-dose irradiation

International Nuclear Information System (INIS)

Defresne, M.P.; Greimers, R.; Lenaerts, P.; Boniver, J.

1986-01-01

A split-dose regimen of whole-body irradiation (4 X 175 rad at weekly intervals) induced thymic lymphomas in C57BL/Ka mice after a latent period of 3-9 months. Meanwhile, preleukemia cells arose in the thymus and bone marrow and persisted until the onset of lymphomas. Simultaneously, thymic lymphopoiesis was impaired; thymocyte numbers were subnormal and thymic nurse cells disappeared in a progressive but irreversible fashion. The depletion of these lymphoepithelial complexes, which are normally involved in the early steps of thymic lymphopoiesis, was related to altered prothymocyte activity in bone marrow and to damaged thymic microenvironment, perhaps as a consequence of the presence of preleukemia cells. The grafting of normal bone marrow cells after irradiation prevented the development of lymphomas. However, marrow reconstitution did not inhibit the induction of preleukemia cells. They disappeared from the thymus during the second part of the latent period. At the same time, thymic lymphopoiesis was restored; thymocytes and nurse cell numbers returned to normal as a consequence of the proliferation of grafted marrow-derived cells within the thymus. The results thus demonstrated an intimate relationship between preleukemia cells and an alteration of thymic lymphopoiesis, which particularly involved the nurse cell microenvironment. Some preleukemia cells in marrow-reconstituted, irradiated mice derived from the unirradiated marrow inoculate. Thus these cells acquired neoplastic potential through a factor present in the irradiated tissues. The nature of this indirect mechanism was briefly discussed

Implantation of cultured thymic fragments in patients with acquired immunodeficiency syndrome

NARCIS (Netherlands)

Danner, S. A.; Schuurman, H. J.; Lange, J. M.; Gmelig Meyling, F. H.; Schellekens, P. T.; Huber, J.; Kater, L.

1986-01-01

Cultured thymic fragments were implanted in one patient with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and in eight AIDS patients with opportunistic infections (OIs, four patients), Kaposi's sarcoma (KS, two patients), or both (two patients). Thereafter, objective clinical

Esophageal bypass after failed chemoradiotherapy for unresectable esophageal cancer

International Nuclear Information System (INIS)

Matono, Satoru; Tanaka, Toshiaki; Mori, Naoki; Nagano, Takeshi; Fujita, Hiromasa; Shirouzu, Kazuo

2013-01-01

Esophageal stenosis and/or fistula often occur after chemoradiotherapy (CRT) for unresectable esophageal cancer. In such patients, an esophageal stent can help achieve oral intake. However an esophageal stent cannot be inserted where there is complete stenosis or where the tumor is located. In such cases, esophageal bypass surgery may be necessary. Here, we investigated the clinical characteristics and outcomes in patients who underwent esophageal bypass surgery in our institution. We reviewed 10 cases of esophageal bypass surgery (gastric tube in 8 cases, colon in 2 cases) after CRT for unresectable esophageal cancer, between 2001 and 2009. There were 5 of stenosis-only cases, 4 fistula-only cases, and 1 case of stenosis and fistula. There were postoperative complications in 5 cases (50%), and all these were treated conservatively and healed. The median survival from surgery to peroral intake was 20 days (range 9-90 days), and the median survival after starting peroral intake was 130 days (range 48-293 days). Esophageal bypass surgery can achieve good performance status and improve peroral intake. (author)

Radiation therapy for unresectable locally advanced breast cancer

International Nuclear Information System (INIS)

Horikawa, Noriko; Inoue, Masayoshi; Uehara, Tomoko; Miyasaka, T.; Miyasaka, M.; Tabata, Yoji; Sakamoto, Nobuyuki; Nakagawa, Y.

2013-01-01

Thirteen cases of inoperable advanced breast cancer were treated with radiotherapy between 2002 to 2012 at Nara Prefectural Hospital. All cases were treated by radiotherapy and chemo-endocrine therapy. Patients received 60-81 Gy (median 60 Gy) to the primary breast tumor. Response of the breast tumors were complete response in 3 cases (23%), partial response in 8 cases (62%) and stable disease in 2 cases (15%) (response rate: 85%). All breast tumors had been controlled and skin troubles were reduced. Radiotherapy for breast cancer is useful for primary tumor control and improved quality of life (QOL). Radiotherapy should be considered to be useful modality in the treatment of advanced breast cancer. (author)

IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

NARCIS (Netherlands)

Saluja, Rohit; Zoltowska, Anna; Ketelaar, Maria Elizabeth; Nilsson, Gunnar

2016-01-01

Thymic Stromal Lymphopoietin (TSLP) and Interleukin 33 (IL-33) are two cytokines released by cells that are in proximity to our environment, e.g., keratinocytes of the skin and epithelial cells of the airways. Pathogens, allergens, chemicals and other agents induce the release of TSLP and IL-33,

Biliary stenting and anti-cancer therapy for unresectable hilar bile duct carcinomas

International Nuclear Information System (INIS)

Saito, Hiroya; Hokotate, Hirofumi; Takeuchi, Shyuhei; Takamura, Akio

2007-01-01

At present, although imaging diagnosis has been developed, most hilar bile duct cancer is still diagnosed at an advanced stage and its prognosis is generally poor. In hilar bile duct cancer, radiotherapy and other several therapies, for example-chemotherapy, arterial-infusion chemotherapy, photodynamic therapy, etc-are being performed for non-operative cases. But standard therapies for this cancer has not been established yet. On the other hand, metallic stents (MS) have been widely used to relieve biliary obstructions as an alternative to plastic prostheses and conventional drainage. The use of MS offers good palliation in hilar bile duct cancer, but patients selection is a key to obtain good results. In this article we reviewed previous studies and clinical trials regarding the anti-cancer therapy and biliary stenting for unresectable hilar bile duct cancer. And optimal therapeutic strategy for hilar bile duct cancer is proposed, primarily based on present views. (author)

Osseous oligometastases from thymic carcinoma: a case report suggesting the effectiveness of palliative-intent radiotherapy treatment

Directory of Open Access Journals (Sweden)

Kashima J

2016-02-01

Full Text Available Jumpei Kashima,1 Hirotoshi Horio,1 Yusuke Okuma,1,2 Yukio Hosomi,1 Tsunekazu Hishima3 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; 2Division of Oncology, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan; 3Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan Background: Oligometastasis, a recently proposed concept, is defined as an intermediate state of cancer, between localized and systemic disease, that may be well controlled by local ablative treatment. Thymic carcinoma is a rare cancer with a poor prognosis. A definitive management approach has yet to be confirmed by a high level of evidence.Case presentation: We present the case of a 41-year-old female who underwent curative-intent surgery for a stage III squamous cell carcinoma of the thymus. Bone metastases were detected 1 year later by magnetic resonance imaging. These were treated with palliative-intent radiotherapy. Disease progression has not been observed in more than 15 years since the achievement of complete radiological remission.Conclusion: The treatment outcomes in this and other reported cases suggest that some patients with oligometastatic thymic carcinoma may achieve prolonged survival or even cure with low-dose radiotherapy delivered to the metastases. Keywords: oligometastasis, thymic carcinoma, thymic epithelial tumor, bone metastasis

Thymic size at birth in preterm infants with severe respiratory ...

African Journals Online (AJOL)

The only maternal and postnatal factors influencing CT/T ratio were the presence of pre-eclamptic toxaemia (PET) and birth by caesarean section (CS), but these factors did not influence likelihood of survival. Factors found to be not associated with thymic size were antenatal steroid administration, maternal HIV status, ...

Combined treatment of unresectable pancreatic carcinoma

International Nuclear Information System (INIS)

Ohashi, Kazuhiko; Yamao, Kenji; Watanabe, Yoshihiro; Morimoto, Takeshi

1999-01-01

For patients with unresectable pancreatic carcinoma, a few kind of treatment including chemoradiation, intraoperative radiation and intra-arterial chemotherapy was done. Chemoradiation using 5FU, CDDP, ADM and radiation to the lesion and liver was performed in 16 patients, showing a response rate of 10%. One-year survivals rate and mean a survival period of this group was 11.7% and 6.6 months respectively. Postmortem autopsy in 6 cases revealed insufficient therapeutic effects in both primary and metastatic site. Because of above-mentioned reasons, chemoradiation therapy to the pancreatic carcinoma, which we did, was estimated as ineffective. (author)

Irreversible electroporation of locally advanced solid pseudopapillary carcinoma of the pancreas: A case report

Directory of Open Access Journals (Sweden)

Luciano Tarantino

2018-04-01

Full Text Available Introduction: Solid pseudopapillary Carcinoma (SPC is a rare pancreatic Tumor with variable, usually low, malignancy potential. Howewer, several SPC are associated with aggressive behavior, local vascular infiltration, organ invasion, distant metastasis, and can be unresectable. Irreversible Electroporation (IRE is an emerging non-thermal ablation technique for the treatment of locally advanced pancreatic carcinoma. We report the results of four year disease-free follow-up in a case of locally advanced unresectable SPC treated with IRE. Presentation of case: A 24-year female patient with SPC of the pancreas underwent IRE during laparotomy under general anesthesia with intubation. Computed Tomography (CT showed complete tumor thrombosis of splenic vein, encasement of celiac artery and mesenteric vein. Six insertions of 3–4 electrodes per insertion were performed. One month-CT-control showed shrinkage of the tumor. 6 months-post-treatment imaging showed complete regression of the mass, patent Splenic/mesenteric veins, absence of local recurrence or distant metastasis. Post treatment CTs at 12-18-24-30-36-42-48 months follow-up confirmed absence of local or distant recurrence. Discussion: Surgery is the first choice curative treatment of SPC. Howewer aggressive surgery (duodeno-pancreasectomy in unresectable cases, may have a high risk of recurrences, morbidities and death, and bring concerns about endocrine and exocrine insufficiency in a young patient. In these cases, IRE could be a safe and effective alternative treatment and could realize, in selected cases, the condition for a radical surgery, and a bridge to R-0 resection. Conclusions: IRE could represent an effective alternative therapy to surgery in local advanced, unresectable SPC. Keywords: Pancreatic neoplasm, Solid papillary carcinoma, Intraoperative ultrasound, Irreversible electroporation, Case report

The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis; Dignostikk av tymom og thymusatrofi hos pasienter med myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E. [Haukeland Sykehus, Bergen (Norway)

1997-11-01

The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs.

Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation

International Nuclear Information System (INIS)

Zuniga-Pfluecker, J.C.K.; Kruisbeek, A.M.

1990-01-01

Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4-/CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells

Application of multidisciplinary treatment using chemoradiotherapy for advanced esophageal cancer and problems thereof

International Nuclear Information System (INIS)

Osaka, Yoshiaki; Takagi, Yuu; Hoshino, Sumito; Shinohara, M.; Ogata, Takashi; Tsuchida, Akihiko; Aoki, Tatsuya

2007-01-01

Application of multidisciplinary treatment using chemoradiotherapy (CRT) for advanced esophageal cancer and the problems thereof were examined by stage. Subjects consisted of 169 cases of patients with advanced esophageal cancer who underwent CRT from 1998 to 2004 (stage III/IVa/IVb: 102/55/12 cases). Mean age was 63.4 years old, and male-to-female ratio was 145: 24. In all cases, low dose FP+radiation 40 Gy (4 weeks) was performed. Surgery was performed for resectable cases, and additional irradiation of 20-30 Gy for unresectable cases and those who refused surgery. Considerations included percentage of effectiveness, side effects, and prognosis. Side effects: Low white blood cell (WBC) was 65.1%, esophagitis was 30.2%, anemia was 21.3%, and thrombocytopenia was 12.4%. Stage III: Percentage of effectiveness was 52.0%. Survival rate of 5: 51.0% for resected cases (n=69) and 16.8% for unresected cases (n=33) (p=0.0002). Reasons for unresection: 17 cases of refusal of surgery, 11 cases comprising physical reasons, and 5 cases of others. Stage IVa: The percentage of effectiveness was 45.4%. Survival rate of 5: 23.1% in resected cases (n=13), and 9.8% in unresected cases (n=42). Stage IVb (all cases unresected): The percentage of effectiveness was 25.0%. Survival rate of 1: 11.7%. Survival rate of 2: 0%. In stage III, if prognosis of resected cases after CRT was good and resection was possible after CRT, surgery was desirable. In stage IVa, if it is a single organ T4 case, resection is possible after CRT, which is a good application of CRT. The stage IVb prognosis is poor, so chemotherapy with new regimens should be considered. (author)

External and intraoperative radiotherapy for resectable and unresectable pancreatic cancer: analysis of survival rates and complications

International Nuclear Information System (INIS)

Nishimura, Yasumasa; Hosotani, Ryo; Shibamoto, Yuta; Kokubo, Masaki; Kanamori, Shuichi; Sasai, Keisuke; Hiraoka, Masahiro; Ohshio, Gakuji; Imamura, Masayuki; Takahashi, Masaji; Abe, Mitsuyuki

1997-01-01

Purpose: Clinical results of intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for both resectable and unresectable pancreatic cancer were analyzed. Methods and Materials: Between 1980 and 1995, 332 patients with pancreatic cancer were treated with surgery and/or radiation therapy (RT). Of the 332 patients, 157 patients were treated with surgical resection of pancreatic tumor, and the remaining 175 patients had unresectable pancreatic tumors. Among the 157 patients with resected pancreatic cancer, 62 patients were not treated with RT, while 40 patients were treated with EBRT alone (mean RT dose; 46.3 Gy) and 55 patients with IORT (25.2 Gy) ± EBRT (44.0 Gy). On the other hand, among the 175 patients with unresectable pancreatic cancer, 58 patients were not treated with RT, 46 patients were treated with EBRT alone (39.2 Gy), and the remaining 71 patients with IORT (29.3 Gy) ± EBRT (41.2 Gy). Results: For 87 patients with curative resection, the median survival times (MSTs) of the no-RT, the EBRT, and the IORT ± EBRT groups were 10.4, 13.0, and 15.5 months, respectively, without significant difference. For 70 patients with non curative resection, the MSTs of the no-RT, the EBRT, and the IORT ± EBRT groups were 5.3, 8.7, and 6.5 months, respectively. When the EBRT and the IORT ± EBRT groups were combined, the survival rate was significantly higher than that of the no RT group for non curatively resected pancreatic cancers (log rank test; p = 0.028). The 2-year survival probability of the IORT ± EBRT group (16%) was higher than that of the EBRT group (0%). For unresectable pancreatic cancer, the MSTs of 52 patients without distant metastases were 6.7 months for palliative surgery alone, 7.6 months for EBRT alone, and 8.2 months for IORT ± EBRT. The survival curve of the IORT ± EBRT group was significantly better than that of the no-RT group (p 2 years) were obtained by IORT ± EBRT for non curatively resected and unresectable pancreatic

Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas - Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c.

Science.gov (United States)

Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A; Rieker, Ralf J; Körner, Daniel; Nix, Wilfred; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

2013-01-01

The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

Acute Respiratory Distress due to Thymoma in a Patient Treated with TK Inhibitor: A Case Report and Review of the Current Treatment Options

Directory of Open Access Journals (Sweden)

P. Zarogoulidis

2011-03-01

Full Text Available Thymic malignancies are rare intrathoracic tumors that may be aggressive and difficult to treat in advanced stage. Surgery is the cornerstone of the management of thymomas: it is significant for the definite histopathological diagnosis and staging, and in most cases, it constitutes the first step of the treatment strategy. For patients with primary unresectable thymomas, the multimodal treatment schedule nowadays includes neoadjuvant chemotherapy, extensive surgery, adjuvant radiotherapy, and in some cases, adjuvant chemotherapy. A patient with a history of stage III COPD and an undiagnosed thoracic mass was admitted to the intensive care unit with acute respiratory distress. A radiologic evaluation by CT scan revealed a mass of 13 cm in diameter at the mediastinum. Fine needle aspiration was performed and revealed a thymoma. Due to poor performance status, the patient was not able to undergo surgery. He refused to be treated with neither chemotherapy nor radiotherapy, but due to EGFR overexpression, treatment with TK inhibitor was suggested. Fine needle aspiration biopsy is commonly used to identify metastasis to the mediastinum. However, it is less often employed as a primary diagnostic tool for tumors, particularly thymic neoplasms. The use of targeted therapies for the treatment of thymic malignancies has been described in the literature. Over the past years, significant efforts have been made to dissect the molecular pathways involved in the carcinogenesis of these tumors. Insights have been obtained following anecdotal clinical responses to targeted therapies, and large-scale genomic analyses have been conducted.

Palliative Interventional and Surgical Therapy for Unresectable Pancreatic Cancer

International Nuclear Information System (INIS)

Assfalg, Volker; Hüser, Norbert; Michalski, Christoph; Gillen, Sonja; Kleeff, Jorg; Friess, Helmut

2011-01-01

Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis), the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually

Palliative Interventional and Surgical Therapy for Unresectable Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Assfalg, Volker; Hüser, Norbert; Michalski, Christoph; Gillen, Sonja; Kleeff, Jorg; Friess, Helmut, E-mail: friess@chir.med.tu-muenchen.de [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, D-81675 Munich (Germany)

2011-02-14

Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis), the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually.

[Three Cases of Unresectable, Advanced, and Recurrent Colorectal Cancer Associated with Gastrointestinal Obstruction That Were Treated with Small Intestine-Transverse Colon Bypass Surgery].

Science.gov (United States)

Ida, Arika; Miyaki, Akira; Miyauchi, Tatsuomi; Yamaguchi, Kentaro; Naritaka, Yoshihiko

2016-11-01

Herein, we report 3cases of unresectable, advanced, and recurrent colorectal cancer associated with gastrointestinal obstruction. The patients were treated with small intestine-transverse colon bypass surgery, which improved the quality of life (QOL)in all cases. Case 1 was an 80-year-old woman who presented with subileus due to ascending colon cancer. After surgery, her oral intake was reestablished, and she was discharged home. Case 2 was an 89-year-old woman whose ileus was caused by cecal cancer with multiple hepatic metastases. After surgery, the patient was discharged to a care facility. Case 3 was an 83-year-old man whose ileus was caused by a local recurrence and small intestine infiltration after surgery for rectosigmoid cancer. He underwent surgery after a colonic stent was inserted. His oral intake was re-established and he was discharged home. Small bowel-transverse colon bypass surgery can be used to manage various conditions rostral to the transverse colon. It is still possible to perform investigations in patients whose general condition is poorer than that of patients who undergo resection of the primary lesion. This avoids creating an artificial anus and allows continuation of oral intake, which are useful for improving QOL in terminal cases.

Proton Beam Therapy for Unresectable Malignancies of the Nasal Cavity and Paranasal Sinuses

Energy Technology Data Exchange (ETDEWEB)

Zenda, Sadamoto, E-mail: szenda@east.ncc.go.jp [Division of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Kohno, Ryosuke; Kawashima, Mitsuhiko; Arahira, Satoko; Nishio, Teiji [Division of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Tahara, Makoto [Division of Gastrointestinal Oncology and Endoscopy, National Cancer Center Hospital East, Chiba (Japan); Hayashi, Ryuichi [Division of Head and Neck Surgery, National Cancer Center Hospital East, Chiba (Japan); Kishimoto, Seiji [Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo (Japan); Ogino, Takashi [Division of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan)

2011-12-01

Purpose: The cure rate for unresectable malignancies of the nasal cavity and paranasal sinuses is low. Because irradiation with proton beams, which are characterized by their rapid fall-off at the distal end of the Bragg peak and sharp lateral penumbra, depending on energy, depth, and delivery, provide better dose distribution than X-ray irradiation, proton beam therapy (PBT) might improve treatment outcomes for conditions located in proximity to risk organs. We retrospectively analyzed the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: We reviewed 39 patients in our database fulfilling the following criteria: unresectable malignant tumors of the nasal cavity, paranasal sinuses or skull base; N0M0 disease; and treatment with PBT (>60 GyE) from January 1999 to December 2006. Results: Median patient age was 57 years (range, 22-84 years); 22 of the patients were men and 17 were women. The most frequent primary site was the nasal cavity (n = 26, 67%). The local control rates at 6 months and 1 year were 84.6% and 77.0%, respectively. With a median active follow-up of 45.4 months, 3-year progression-free and overall survival were 49.1% and 59.3%, respectively. The most common acute toxicities were mild dermatitis (Grade 2, 33.3%), but no severe toxicity was observed (Grade 3 or greater, 0%). Five patients (12.8%) experienced Grade 3 to 5 late toxicities, and one treatment-related death was reported, caused by cerebrospinal fluid leakage Grade 5 (2.6%). Conclusion: These findings suggest that the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses make it is a promising treatment option.

Proton Beam Therapy for Unresectable Malignancies of the Nasal Cavity and Paranasal Sinuses

International Nuclear Information System (INIS)

Zenda, Sadamoto; Kohno, Ryosuke; Kawashima, Mitsuhiko; Arahira, Satoko; Nishio, Teiji; Tahara, Makoto; Hayashi, Ryuichi; Kishimoto, Seiji; Ogino, Takashi

2011-01-01

Purpose: The cure rate for unresectable malignancies of the nasal cavity and paranasal sinuses is low. Because irradiation with proton beams, which are characterized by their rapid fall-off at the distal end of the Bragg peak and sharp lateral penumbra, depending on energy, depth, and delivery, provide better dose distribution than X-ray irradiation, proton beam therapy (PBT) might improve treatment outcomes for conditions located in proximity to risk organs. We retrospectively analyzed the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: We reviewed 39 patients in our database fulfilling the following criteria: unresectable malignant tumors of the nasal cavity, paranasal sinuses or skull base; N0M0 disease; and treatment with PBT (>60 GyE) from January 1999 to December 2006. Results: Median patient age was 57 years (range, 22–84 years); 22 of the patients were men and 17 were women. The most frequent primary site was the nasal cavity (n = 26, 67%). The local control rates at 6 months and 1 year were 84.6% and 77.0%, respectively. With a median active follow-up of 45.4 months, 3-year progression-free and overall survival were 49.1% and 59.3%, respectively. The most common acute toxicities were mild dermatitis (Grade 2, 33.3%), but no severe toxicity was observed (Grade 3 or greater, 0%). Five patients (12.8%) experienced Grade 3 to 5 late toxicities, and one treatment-related death was reported, caused by cerebrospinal fluid leakage Grade 5 (2.6%). Conclusion: These findings suggest that the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses make it is a promising treatment option.

Effect of pretreatment psoas muscle mass on survival for patients with unresectable pancreatic cancer undergoing systemic chemotherapy.

Science.gov (United States)

Ishii, Noriko; Iwata, Yoshinori; Nishikawa, Hiroki; Enomoto, Hirayuki; Aizawa, Nobuhiro; Ishii, Akio; Miyamoto, Yuho; Yuri, Yukihisa; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Yoh, Kazunori; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Takata, Ryo; Iijima, Hiroko; Nishiguchi, Shuhei

2017-11-01

To the best of our knowledge, there are few previous studies that have investigated the effect of decreased skeletal muscle mass (DSMM) on survival in patients with unresectable advanced pancreatic cancer (APC) who are undergoing systemic chemotherapy. Thus, the present study aimed to investigate the impact of DSMM, as determined by the psoas muscle index (PMI) following computed tomography and prior to systemic chemotherapy, on the outcomes of patients with unresectable APC (n=61). The primary endpoint used was the overall survival (OS) rate. The OS rates in the PMI-High group (exceeds the median PMI value in each gender) were retrospectively compared with those in the PMI-Low group (below the median PMI value in each gender), and factors associated with OS were investigated using univariate and multivariate analyses. The study cohort included 31 male and 30 female patients with a median age of 72 years, 13 of whom were stage IVA, and 48 were stage IVB. The median PMI in males was 4.3 cm 2 /m 2 (range, 1.6-8.2 cm 2 /m 2 ), while that in females was 2.3 cm 2 /m 2 (range, 0.7-6.1 cm 2 /m 2 ). The proportion of patients with performance status 0 in the PMI-High group was significantly high, compared with that in the PMI-Low group [83.3% (25/30) vs. 58.1% (18/31); P=0.0486]. Body mass index in the PMI-High group was significantly higher compared with that in the PMI-Low group (P=0.0154). The 1-year cumulative survival rate was 43.3% in the PMI-High group and 12.9% in the PMI-Low group (P=0.0027). Following multivariate analysis, PMI (P=0.0036), prothrombin time (P=0.0044) and carbohydrate antigen 19-9 (P=0.0451) were identified to be significant predictors of OS. In conclusion, DSMM, as determined by the PMI, could be a significant predictor of prognosis in patients with unresectable APC who are receiving systemic chemotherapy.

Fate of thymic lymphocytes. [/sup 125/IudR and /sup 3/HTdR tracer studies in mice

Energy Technology Data Exchange (ETDEWEB)

Laissue, J A; Chanana, A D; Cronkite, E P; Joel, D D

1976-01-01

Data are summarized from a number of studies on the fate of thymic lymphocytes. Results are reported from studies in mice in which /sup 125/IudR and /sup 3/HTdR were used as tracers to study the production, maturation, migration, and life span of thymic lymphocytes. It is pointed out that thymus-derived cells constitute the majority of recirculating lymphocytes and that peripheral, differentiated thymus-derived lymphocytes exhibit a number of immunological functions. 114 references.

Case Report: CT diagnosis of thymic remnant cyst/thymopharyngeal duct cyst

International Nuclear Information System (INIS)

Daga, Bipin V; Chaudhary, VA; Dhamangaokar, VB

2009-01-01

A 4-year-old boy presented with history of left anterolateral neck swelling since birth. He was clinically diagnosed to have a branchial cleft cyst. A CT scan revealed findings suggestive of a thymic remnant cyst. The lesion was excised and the diagnosis was confirmed by histopathology

Palliative treatment with radiation-emitting metallic stents in unresectable Bismuth type III or IV hilar cholangiocarcinoma.

Science.gov (United States)

Lu, Jian; Guo, Jin-He; Zhu, Hai-Dong; Zhu, Guang-Yu; Wang, Yong; Zhang, Qi; Chen, Li; Wang, Chao; Pan, Tian-Fan; Teng, Gao-Jun

2017-01-01

The emerging data for stenting in combination with brachytherapy in unresectable hilar cholangiocarcinoma are encouraging. The aim of this study was to evaluate the efficacy and safety of radiation-emitting metallic stents (REMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma. Consecutive patients who underwent percutaneous placement with REMS or uncovered self-expandable metallic stent (SEMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma between September 2011 and April 2016 were identified into this retrospective study. Data on patient demographics and overall survival, functional success, stent patency and complications were collected at the authors' hospital. A total of 59 patients were included: 33 (55.9%) in the REMS group and 26 (44.1%) in the SEMS group. The median overall survival was 338 days in the REMS group and 141 days in the SEMS group (philar cholangiocarcinoma, and seems to prolong survival as well as patency of stent in these patients.

Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

Energy Technology Data Exchange (ETDEWEB)

Tribius, Silke; Kilic, Yasemin [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kronemann, Stefanie [Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schroeder, Ursula [Dept. of Head and Neck Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Hakim, Samer [Dept. of Oro-Maxillo-Facial Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Rades, Dirk [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany)

2009-10-15

Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m{sup 2}/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m{sup 2}/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas – Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c

Science.gov (United States)

Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A.; Rieker, Ralf J.; Körner, Daniel; Nix, Wilfred; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

2013-01-01

The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC. PMID:24427739

Factors associated with thymic size at birth among low and normal birth-weight infants

DEFF Research Database (Denmark)

Eriksen, Helle Brander; Biering-Sørensen, Sofie; Lund, Najaaraq

2014-01-01

treatment at the time of labor (0.84 [0.70-1.00]), number of pregnancy consultations (1.03 [1.00-1.05]), maternal age (0.91 [0.84-0.98]), Apgar score (1.06 [1.03-1.10]), and infant convulsions (0.44 [0.29-0.65]) were all independent determinants of thymic index but not all were determinants of thymus....../weight index. Pathologic amniotic fluid and cesarean delivery were associated with thymus/weight index among LBW infants (0.85 [0.75-0.95] and 0.80 [0.67-0.96]) but were only borderline significant for thymic index. CONCLUSION: Exposures mainly related to stress and infections were associated with a smaller...

Randomized Phase II Study of Pemetrexed, Carboplatin, and Thoracic Radiation With or Without Cetuximab in Patients With Locally Advanced Unresectable Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 30407

Science.gov (United States)

Govindan, Ramaswamy; Bogart, Jeffrey; Stinchcombe, Thomas; Wang, Xiaofei; Hodgson, Lydia; Kratzke, Robert; Garst, Jennifer; Brotherton, Timothy; Vokes, Everett E.

2011-01-01

Purpose Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients and Methods Patients with unresectable stage III non–small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ≥ 55%, the regimen(s) would be considered for further study. Results Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. Conclusion The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC. PMID:21747084

The Wnt Signaling Antagonist Kremen1 is Required for Development of Thymic Architecture

Directory of Open Access Journals (Sweden)

Masako Osada

2006-01-01

Full Text Available Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs. Kremen1 (Krm1 is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk by competing for the lipoprotein receptor-related protein (LRP-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2 stage and continuing until the CD4+CD8+(DP stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1− / − mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5 Keratin 8+(K8 stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1− / − mice, when compared with krm1+ / + derived TEC lines. Fluorescence activated cell sorting (FACS analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1+EpCAM+ and medullary (UEA-1+ EpCAMhi epithelial subsets, within the krm1− / − thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1− / − mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.

Vandetanib in advanced medullary thyroid cancer: review of adverse event management strategies

DEFF Research Database (Denmark)

Grande, Enrique; Kreissl, Michael C; Filetti, Sebastiano

2013-01-01

Vandetanib has recently demonstrated clinically meaningful benefits in patients with unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). Given the potential for long-term vandetanib therapy in this setting, in addition to treatment for disease-related symptoms, effective...

Clinical impact of radiotherapy for locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Sawaki, Akira; Hoki, Noriyuki; Ito, Satoko

2009-01-01

Although a randomized controlled trial for locally advanced pancreatic cancer (PC) has demonstrated a survival advantage for treatment with gemcitabine alone, chemoradiotherapy remains the treatment of choice for locally advanced disease in Japan. The aim of this study was to compare the survival benefits associated with gemcitabine and concurrent chemoradiotherapy in locally advanced unresectable PC. Seventy-seven patients with locally advanced unresectable PC were retrospectively enrolled from April 2001 to December 2006. All cases were histologically proven, and patients received gemcitabine chemotherapy (n=30) or concurrent chemoradiotherapy (based on 5-fluorouracil, n=28, or gemcitabine, n=19, as a radiosensitizer) at Aichi Cancer Center Hospital. Patients who received chemoradiotherapy had significantly better performance status than those who had chemotherapy. Tumor response was 0% for chemotherapy and 13% chemoradiotherapy, but survival benefit was similar among patients in the chemotherapy group (overall response (OS) 12 months; progression-free survival (PFS), 3 months) and those in the chemoradiotherapy group (OS, 13 months; PFS, 5 months). Two-year survival was 21% for chemotherapy patients and 19% for chemoradiotherapy patients. Severe toxicities (Grade 3-4 National Cancer Institute-Common Toxicity Criteria, version 3.0) were significantly more frequent for chemoradiotherapy than for chemotherapy. Gemcitabine chemotherapy showed similar survival benefit compared to 5-fluorouracil- and gemcitabine-based chemoradiotherapy. (author)

Detection of chemotherapy-induced thymic changes in patients with metastasised testicular tumors by computed tomography

International Nuclear Information System (INIS)

Hendrickx, P.; Doehring, W.

1989-01-01

Serial thoracic CT scans of 100 patients suffering from testicular cancer revealed that the thymus appears to atrophy temporarily during administration of cytostatic agents. About two months after cessation of chemotherapy rebound enlargement of the thymus occurs and persists for about two years followed by a slow involution. Using a semiquantitative score system, thymic CT images of these patients were compared with that of 100 patients suffering from other malignancies, 100 patients without malignant disease and 52 patients with myasthenia gravis, taking into account the age-related changes of the size of the organ. Rebound thymic enlargement should not be misinterpreted as metastatic lymph nodes. (orig.) [de

Detection of chemotherapy-induced thymic changes in patients with metastasised testicular tumors by computed tomography

Energy Technology Data Exchange (ETDEWEB)

Hendrickx, P.; Doehring, W.

1989-03-01

Serial thoracic CT scans of 100 patients suffering from testicular cancer revealed that the thymus appears to atrophy temporarily during administration of cytostatic agents. About two months after cessation of chemotherapy rebound enlargement of the thymus occurs and persists for about two years followed by a slow involution. Using a semiquantitative score system, thymic CT images of these patients were compared with that of 100 patients suffering from other malignancies, 100 patients without malignant disease and 52 patients with myasthenia gravis, taking into account the age-related changes of the size of the organ. Rebound thymic enlargement should not be misinterpreted as metastatic lymph nodes.

Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

2016-06-15

To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.

Science.gov (United States)

Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J; Chapman, Harold D; Serreze, David V; DiLorenzo, Teresa P

2018-04-09

Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles. Copyright © 2018 by The American Association of Immunologists, Inc.

Carbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas

International Nuclear Information System (INIS)

Serizawa, Itsuko; Kagei, Kenji; Kamada, Tadashi; Imai, Reiko; Sugahara, Shinji; Okada, Tohru; Tsuji, Hiroshi; Ito, Hisao; Tsujii, Hirohiko

2009-01-01

Purpose: To evaluate the applicability of carbon ion radiotherapy (CIRT) for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control. Methods and Materials: From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcoma received CIRT. Age ranged from 16 to 77 years (median, 48.6 years). Of the patients, 16 had primary disease and 8 recurrent disease. Histologic diagnoses were as follows: malignant fibrous histiocytoma in 6, liposarcoma in 3, malignant peripheral nerve sheath tumor in 3, Ewing/primitive neuroectodermal tumor (PNET) in 2, and miscellaneous in 10 patients. The histologic grades were as follows: Grade 3 in 15, Grade 2-3 in 2, Grade 2 in 3, and unknown in 4. Clinical target volumes ranged between 57 cm 3 and 1,194 cm 3 (median 525 cm 3 ). The delivered carbon ion dose ranged from 52.8 to 73.6 GyE in 16 fixed fractions over 4 weeks. Results: The median follow-up was 36 months (range, 6-143 months). The overall survival rates at 2 and 5 years were 75% and 50%, respectively. The local control rates at 2 and 5 years were 77% and 69%. No complications of the gastrointestinal tract were encountered. No other toxicity greater than Grade 2 was observed. Conclusions: Use of CIRT is suggested to be effective and safe for retroperitoneal sarcomas. The results obtained with CIRT were a good overall survival rate and local control, notwithstanding the fact that most patients were not eligible for surgical resection and had high-grade sarcomas.

Concurrent chemotherapy and radiation therapy for unresectable locally advanced carcinoma of the esophagus. Phase II study and clinical review on literature

International Nuclear Information System (INIS)

Fritz, P.; Stoll, P.; Wannenmacher, M.; Zierhut, D.

2003-01-01

Background: Neither surgical advances nor those in therapeutic radiology have been able to significantly reduce the mortality related to esophageal carcinomas. The results of combining: first surgery, then radiation therapy, which have been dissatisfactory for decades, encourage therapeutic concepts involving a variety of modalities. Patients and Methods: For 50 patients with unresectable locally advanced esophageal carcinomas, a palliative concurrent chemotherapy and radiation therapy was carried out according to the ''intent to treat'' principle. The aim was a minimal dose of 40 Gy. The concurrent chemotherapy was carried out using cisplatin/5-FU during the 1st and 4th weeks of radiation therapy. In the case of partial or complete remission, the chemotherapy was to be continued as maintenance therapy with a maximum of four cycles. In the case of no change or minor response, instead of maintenance chemotherapy, the dose of local radiation was to be increased by means of brachytherapy. Results: The median survival rate for the entire population under study was 8.7 months. The survival rates of 1, 2, 3, 4, and 5 years were, respectively, 38%, 20.5%, 13.7%, 6.8%, and 6.8%. The remission rates were as follows: NC: 14 patients (28%), PR: 32 patients (64%), CR: 4 patients (8%). 17 patients (34%) tolerated the full concurrent chemotherapy; only twelve patients (24%) tolerated supportive chemotherapy. The following factors exhibited a significant correlation to survival: the intensity of the chemotherapy, the Karnofsky index, the age of the patients, and the improvement of oral food intake. Conclusions: The concurrent chemotherapy was toxic and the benefit to the patients questionable. At best, meta-analyses of randomized studies along the lines of ''evidence-based medicine'' demonstrate for concurrent chemotherapy and radiation therapy an improvement of 2-year survival rates, but with these also involving a high level of toxicity. Due to the heterogeneous data available

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.

Science.gov (United States)

Bond, Jonathan; Marchand, Tony; Touzart, Aurore; Cieslak, Agata; Trinquand, Amélie; Sutton, Laurent; Radford-Weiss, Isabelle; Lhermitte, Ludovic; Spicuglia, Salvatore; Dombret, Hervé; Macintyre, Elizabeth; Ifrah, Norbert; Hamel, Jean-François; Asnafi, Vahid

2016-06-01

Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemias, but it is unclear whether these constitute a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA-positive cases among 209 patients with adult T-cell acute lymphoblastic leukemia uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA-positive patients had markedly higher rates of an early thymic precursor-like immunophenotype (40.8% versus 14.5%, P=0.0004), chemoresistance (59.3% versus 40.8%, P=0.026) and positivity for minimal residual disease (48.5% versus 23.5%, P=0.01) than the HOXA-negative group. These differences were due to particularly high frequencies of chemoresistant early thymic precursor-like acute lymphoblastic leukemia in HOXA-positive cases harboring fusion oncoproteins that transactivate HOXA Strikingly, the presence of an early thymic precursor-like immunophenotype was associated with marked outcome differences within the HOXA-positive group (5-year overall survival 31.2% in HOXA-positive early thymic precursor versus 66.7% in HOXA-positive non-early thymic precursor, P=0.03), but not in HOXA-negative cases (5-year overall survival 74.2% in HOXA-negative early thymic precursor versus 57.2% in HOXA-negative non-early thymic precursor, P=0.44). Multivariate analysis further revealed that HOXA positivity independently affected event-free survival (P=0.053) and relapse risk (P=0.039) of chemoresistant T-cell acute lymphoblastic leukemia. These results show that the underlying mechanism of HOXA deregulation dictates the clinico-biological phenotype, and that the negative prognosis of early thymic precursor acute lymphoblastic leukemia is exclusive to HOXA-positive patients, suggesting that early treatment intensification is currently

High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma.

Science.gov (United States)

Miura, Yosuke; Kaira, Kyoichi; Sakurai, Reiko; Imai, Hisao; Tomizawa, Yoshio; Sunaga, Noriaki; Minato, Koichi; Hisada, Takeshi; Oyama, Tetsunari; Yamada, Masanobu

2017-10-01

Glucose-regulated protein (GRP) 78/immunoglobulin heavy chain binding protein (BiP) is a member of the endoplasmic reticulum chaperone family, and its role in various types of human malignancies has recently been investigated. However, the clinicopathological characteristics of GRP78/BiP in advanced thymic carcinoma (ATC) remain unknown. We aimed to examine the relationship between GRP78/BiP expression and the clinical outcomes of ATC patients. Thirty-four patients with ATC receiving combination chemotherapy at three institutions between April 1998 and April 2014 were enrolled in this study. We retrospectively collected patient characteristics such as therapeutic efficacy, pathological findings, and survival data from their medical records. We performed immunohistochemical analysis to evaluate the expression of GRP78/BiP in tumor specimens obtained from surgical resection or biopsy. This study included 21 men (68%) and 13 women (32%) with a median age of 62 years (range 36-75 years). GRP78/BiP overexpression was observed in 65% of the patients (22 of 34 patients). There was no correlation between GRP78/BiP expression and any patient characteristic. Patients with a high level of GRP78/BiP expression had significantly longer overall survival (OS) compared to those with a low level (46.2 vs. 16.8 months, p = 0.04). Multivariate analysis demonstrated that a high level of GRP78/BiP expression was an independent prognostic factor for prolonged OS. Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.

Thymic stromal lymphopoietin as a novel mediator amplifying immunopathology in rheumatic disease

NARCIS (Netherlands)

Hillen, Maarten R.; Radstake, Timothy R. D. J.; Hack, Cornelis E.; van Roon, Joel A. G.

2015-01-01

Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine that has been studied extensively in atopic diseases and more recently in various rheumatic disorders. It is involved in T cell development in the thymus and promotes homeostatic T cell expansion by classical dendritic cells. However,

Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT).

Science.gov (United States)

Turpin, Sophie; Carret, Anne-Sophie; Dubois, Josée; Buteau, Chantal; Patey, Natalie

2015-11-01

The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin. Whole-body F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) was performed to identify a focus of infection. It demonstrated an unusual aspect of the thymus, which led to further investigation and revealed isolated infiltration of the thymus by Langerhans cell histiocytosis. The patient was treated accordingly and is now disease free. As evaluation of Langerhans cell histiocytosis patients with F-18 FDG PET/CT is becoming more frequent, it is important to be aware of the scintigraphical characteristics of thymic Langerhans cell histiocytosis.

Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT)

Energy Technology Data Exchange (ETDEWEB)

Turpin, Sophie [CHU Sainte-Justine, Nuclear Medicine, Montreal (Canada); Carret, Anne-Sophie [CHU Sainte-Justine, Hemato-Oncology, Montreal (Canada); Dubois, Josee [CHU Sainte-Justine, Radiology, Montreal (Canada); Buteau, Chantal [CHU Sainte-Justine, Infectious Diseases, Montreal (Canada); Patey, Natalie [CHU Sainte-Justine, Pathology, Montreal (Canada)

2015-11-15

The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin. Whole-body F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) was performed to identify a focus of infection. It demonstrated an unusual aspect of the thymus, which led to further investigation and revealed isolated infiltration of the thymus by Langerhans cell histiocytosis. The patient was treated accordingly and is now disease free. As evaluation of Langerhans cell histiocytosis patients with F-18 FDG PET/CT is becoming more frequent, it is important to be aware of the scintigraphical characteristics of thymic Langerhans cell histiocytosis. (orig.)

Early thymic T cell development in young transgenic mice overexpressing human Cu/Zn superoxide dismutase, a model of Down syndrome.

Science.gov (United States)

Laurent, Julien; Paly, Evelyne; Marche, Patrice N; London, Jacqueline

2006-06-01

Previous studies have shown that transgenic mice overexpressing Cu/Zn superoxide dismutase, a model of Down syndrome, exhibit premature thymic involution. We have performed a flow cytometry analysis of the developing thymus in these homozygous transgenic mice (hSOD1/hSOD1: Tg-SOD). Longitudinal follow-up analysis from day 3 to day 280 showed an early thymic development in Tg-SOD mice compared with controls. This early thymic development was associated with an increased migration of mature T cells to peripheral lymphoid organs. BrdU labeling showed no difference between Tg-SOD and control mice, confirming that the greater number of peripheral T cells in Tg-SOD mice was not due to extensive proliferation of these cells but rather to a greater pool of emigrant T cells in Tg-SOD.

HTLV-1-infected thymic epithelial cells convey the virus to CD4+ T lymphocytes.

Science.gov (United States)

Carvalho Barros, Luciana Rodrigues; Linhares-Lacerda, Leandra; Moreira-Ramos, Klaysa; Ribeiro-Alves, Marcelo; Machado Motta, Maria Cristina; Bou-Habib, Dumith Chequer; Savino, Wilson

2017-12-01

The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4 + T cells are the main target of HTLV-1, but other cell types are known to be infected, including immature lymphocytes. Developing T cells undergo differentiation in the thymus, through migration and interaction with the thymic microenvironment, in particular with thymic epithelial cells (TEC) the major component of this three dimensional meshwork of non-lymphoid cells. Herein, we show that TEC express the receptors for HTLV-1 and can be infected by this virus through cell-cell contact and by cell-free virus suspensions. The expression of anti-apoptosis, chemokine and adhesion molecules genes are altered in HTLV-1-infected TEC, although gene expression of antigen presentation molecules remained unchanged. Furthermore, HTLV-1-infected TEC transmitted the virus to a CD4 + T cell line and to CD4 + T cells from healthy donors, during in vitro cellular co-cultures. Altogether, our data point to the possibility that the human thymic epithelial cells play a role in the establishment and progression of HTLV-1 infection, functioning as a reservoir and transmitting the virus to maturing CD4 + T lymphocytes, which in turn will cause disease in the periphery. Copyright © 2017. Published by Elsevier GmbH.

Exploring the link between innate immune activation and thymic function by measuring sCD14 and TRECs in HIV patients living in Belgium.

Directory of Open Access Journals (Sweden)

Adrien De Voeght

Full Text Available Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease progression. The goal of this study was to explore the hypothesis of potential links between microbial translocation and thymic function in HIV-1 patients living in Belgium. The extent of microbial translocation was assessed through the measurement of soluble CD14 (sCD14. T-cell receptor excision circles (sjTRECs and dβTRECs were used as a measure of thymic function. Data were collected from 75 HIV-infected patients. Simple and complex linear regressions were done to analyze the link between these two processes. We found a statistically relevant negative correlation between thymopoiesis (sjTREC and sCD14 level (p = 0.004. These results suggest a link between thymic function failure, microbial translocation and innate immune activation.

77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

Science.gov (United States)

2012-04-26

...The Agency for Healthcare Research and Quality (AHRQ) is seeking scientific information submissions from manufacturers of local, minimally invasive, medical devices for unresectable primary hepatocellular carcinoma (e.g., ablation, radiotherapy, or embolization devices). Scientific information is being solicited to inform our Comparative Effectiveness Review of Local Therapies for Unresectable Primary Hepatocellular Carcinoma, which is currently being conducted by the Evidence-based Practice Centers for the AHRQ Effective Health Care Program. Access to published and unpublished pertinent scientific information on this device will improve the quality of this comparative effectiveness review. AHRQ is requesting this scientific information and conducting this comparative effectiveness review pursuant to Section 1013 of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, Public Law 108-173.

Carcinoma of the pancreas: results of irradiation for unresectable lesions

International Nuclear Information System (INIS)

Komaki, R.; Wilson, J.F.; Cox, J.D.; Kline, R.W.

1980-01-01

From 1973 to 1977, 20 patients who had histologically proven unresectable adenocarcinoma of the pancreas with no distant metastases were irradiated at the Medical College of Wisconsin Affiliated Hospitals. The patients received megavoltage external irradiation to minimum tumor doses ranging between 3000 rad in 4 weeks and 5700 rad in 7 weeks (median 4600 rad in 6 weeks); their actuarial survival was 54% at 12 months and 21% at 24 months. Fourteen patients who received 4500 rad or more in 6 to 7 weeks had a median survival of 13 months. Six patients received less than 4500 rad in 3 to 6 weeks, and their median survival was 7 months. At this writing, three patients are alive and apparently disease free more than 2 years after treatment. Complications were seen in two patients. One died from GI bleeding 2 months after completion of radiation therapy, and the other patient developed pancreatic insufficiency. These results and recent reports in the literature show that aggressive irradiation can result in long-term disease free survival in a small proportion of patients with unresectable pancreatic adenocarcinoma. Further exploitation of this approach alone or combined with chemotherapy is warranted

Radioembolization for the treatment of unresectable hepatocellular carcinoma: A clinical review

Institute of Scientific and Technical Information of China (English)

Saad M Ibrahim; Robert J Lewandowski; Kent T Sato; Vanessa L Gates; Laura Kulik; Mary F Mulcahy; Robert K Ryu; Reed A Omary; Riad Salem

2008-01-01

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. The majority of patients with HCC present with unresectable disease. These patients have historically had limited treatment options secondary to HCC demonstrating chemoresistance to the currently available systemic therapies. Additionally, normal liver parenchyma has shown intolerance to tumoricidal radiation doses, limiting the use of external beam radiation. Because of these limitations, novel percutaneous liver-directed therapies have emerged. The targeted infusion of radioactive microspheres (radioembolization) represents one such therapy. Radioembolization is a minimally invasive transcatheter therapy through which radioactive microspheres are infused into the hepatic arteries that supply tumor. Once infused, these microspheres traverse the hepatic vascular plexus and selectively implant within the tumor arterioles. Embedded within the arterioles, the 90Y impregnated microspheres emit high energy and low penetrating radiation doses selectively to the tumor. Radioembolization has recently shown promise for the treatment of patients with unresectable HCC. The objective of this review article is to highlight twocurrently available radioembolic devices (90Y, 188Rh) and provide the reader with a recent review of the literature.

Radioactive self-expanding stents for palliative management of unresectable esophageal cancer: a systematic review and meta-analysis.

Science.gov (United States)

Chen, Hong-Lin; Shen, Wang-Qin; Liu, Kun

2017-05-01

Stent insertion is a feasible and safe palliative management for advanced unresectable esophageal cancer. The aim of this study is to assess the efficacy of radioactive stent for unresectable esophageal cancer compared with conventional stent. Systematic searches of the PubMed and Web of science are dated from their beginning to January 25, 2016. Studies that compared radioactive stent with conventional stent for unresectable esophageal cancer were included. The outcomes were postimplantation survival, relief of dysphagia, and complications related to stent implant. Six studies with 539 patients were included. All of them used stent equipped with radioactive iodine beads as a radioactive stent. The pooled weighted mean difference for median survival was 2.734 months (95% CI 1.710-3.775; Z = 5.21, P = 0.000) between two groups. The 1,3,6 month survival rates were higher in radioactive stents than conventional stent, with the pooled ORs 3.216 (95% CI 1.293-7.999; Z = 2.51, P = 0.012), 3.095 (95% CI 1.908-5.020; Z = 4.58, P = 0.000), and 7.503 (95% CI 2.206- 25.516; Z = 3.23, P = 0.001, respectively). The pooled hazard ratio was 0.464 (95% CI 0.328-0.655; Z = 4.35, P = 0.000) between two groups. For relief of dysphagia, two stents all have good relief of the dysphagia effect, but radioactive stent showed a better effect at 3, 6 months follow-up after implantation. For complications related to stent implant, no significant differences were found between two stents in terms of severe chest pain (30.0% vs. 35.7%, OR 0.765, 95% CI 0.490-1.196), gastroesophageal reflux (18.6% vs. 16.1%, OR 1.188, 95% CI 0.453-3.115), fever (12.1% vs. 12.1%, OR 1.014, 95% CI 0.332-3.097), bleeding (16.7% vs. 14.2%, OR 1.201, 95% CI 0.645-2.236), perforation or fistula (6.1% vs. 9.0%, OR 0.658, 95% CI 0.291-1.486), pneumonia (10.7% vs. 14.1%, OR 0.724, 95% CI 0.343-1.526), stent migration (7.0% vs. 10.2%, OR 0.651, 95% CI 0.220-1.924), and restenosis (24.2% vs. 20.6%, OR 1.228, 95% CI 0

Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer.

Science.gov (United States)

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2009-07-08

Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC). The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC. A systematic review of reports published until September 2008 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials. Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival. Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases. Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24). Currently

PRESENCE OF THYMIC TISSUE IN THE ANTERIOR MEDIASTINAL FATTY TISSUE AND ITS SIGNIFICANCE IN THYMECTOMY FOR MYASTHENIA GRAVIS PATIENT: A CASE REPORT

Directory of Open Access Journals (Sweden)

Athouba

2016-03-01

Full Text Available In 1970s, presence of thymic tissue in anterior mediastinal adipose tissue around the thymus was found. Here we report a case of ectopic thymic tissue in the mediastinum and the possible relevance of this distribution of thymic tissue outside thymus to the therapeutic yield of thymectomies in myasthenia gravis. A 30-year lady with myasthenia gravis (nonthymomatous presented with difficulty in swallowing and breathing for the last 1 years. She was under medical treatment but with little improvement. She underwent extended thymectomy, after which an en bloc resection of the anterior mediastinal fat tissues from pericardium and pleura, including the thymus, was performed. Grossly the soft tissue specimen taken from near left lateral area of heart was fibrofatty tissue. Microscopically isolated thymic tissues were seen interspersed among the fatty tissues composed of mature lymphocytes, epithelial cells and few Hassall's corpuscles were observed. Thymus specimen was within normal histological limits. To ensure complete removal, the adipose tissue at the anterior mediastinum as well as the gross thymus should be removed. Thymic tissue incidence in individual locations was as follows: Retrothyroid, 3(6%; peritracheal, 5 (10%; retrotracheal, 1 (2%; right phrenic nerve, 2 (4%; left phrenic nerve, 14 (28%; right recurrent laryngeal nerve, 2 (4%; left recurrent laryngeal nerve, 2 (4% and periaortic, 0. Trans-sternal thymectomy was found to be beneficial to all patients of mild-to-moderate myasthenia gravis with 70.2% patients showing improvement postoperatively.

Effect of Radiotherapy Planning Complexity on Survival of Elderly Patients With Unresected Localized Lung Cancer

International Nuclear Information System (INIS)

Park, Chang H.; Bonomi, Marcelo; Cesaretti, Jamie; Neugut, Alfred I.; Wisnivesky, Juan P.

2011-01-01

Purpose: To evaluate whether complex radiotherapy (RT) planning was associated with improved outcomes in a cohort of elderly patients with unresected Stage I-II non-small-cell lung cancer (NSCLC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 1998 patients aged >65 years with histologically confirmed, unresected stage I-II NSCLC. Patients were classified into an intermediate or complex RT planning group using Medicare physician codes. To address potential selection bias, we used propensity score modeling. Survival of patients who received intermediate and complex simulation was compared using Cox regression models adjusting for propensity scores and in a stratified and matched analysis according to propensity scores. Results: Overall, 25% of patients received complex RT planning. Complex RT planning was associated with better overall (hazard ratio 0.84; 95% confidence interval, 0.75-0.95) and lung cancer-specific (hazard ratio 0.81; 95% confidence interval, 0.71-0.93) survival after controlling for propensity scores. Similarly, stratified and matched analyses showed better overall and lung cancer-specific survival of patients treated with complex RT planning. Conclusions: The use of complex RT planning is associated with improved survival among elderly patients with unresected Stage I-II NSCLC. These findings should be validated in prospective randomized controlled trials.

Benefit of FOLFOX to unresectable liver metastases secondary from colorectal carcinoma in an oncologic emergency.

Science.gov (United States)

Sugimoto, Maki; Yasuda, Hideki; Koda, Keiji; Yamazaki, Masato; Tezuka, Tohru; Takenoue, Tomohiro; Kosugi, Chihiro; Higuchi, Ryota; Yamamoto, Shiho; Watayo, Yoshihisa; Yagawa, Yohsuke; Suzuki, Masato

2007-09-01

Liver metastasis is an important prognostic factor in colorectal cancer. The efficacy of resection of metastatic lesions in liver metastasis of colorectal cancer is also widely recognized. However, studies on treatment methods of unresectable cases have not been sufficient and obtaining complete remission (CR) for liver metastasis is rare with chemotherapy. Selection of reliable chemotherapy for unresectable liver metastasis is an urgent necessity. The usefulness of oxaliplatin, 5-flurouracil and leucovorin combination therapy (FOLFOX) has recently been reported, but CR of liver metastasis is rare. The current status and new therapeutic significance of FOLFOX therapy are discussed based on the literature of colorectal cancer chemotherapy to date, and the clinical experience in which we obtained CR for liver metastasis is reported. The patient had stage IV rectal cancer, perforative peritonitis, pelvic abscess and simultaneous multiple liver metastasis. The patient underwent an emergency operation using the Hartmann's procedure. Liver metastasis is considered to be a prognostic factor and FOLFOX was selected as the postoperative chemotherapy, CR of the liver metastasis was obtained. FOLFOX was suggested to have new clinical significance in oncologic emergencies against unresectable liver metastasis in colorectal cancer and should serve as adjuvant chemotherapy that will contribute to improvement of treatment results.

Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin

DEFF Research Database (Denmark)

Gelpi, Marco; Hartling, Hans J; Thorsteinsson, Kristina

2016-01-01

was comparable in all groups, and no differences in immune homeostasis were found between primary HIV infection and early presenters, whereas differences in absolute counts and proportions of CD4+ T cell subpopulations were found between primary HIV infection and late presenters. TSLP was elevated in primary HIV...... thymic output, but not with immune recovery. These findings indicate a possible role of TSLP in immune homeostasis in HIV infection but do not support TSLP to affect immune recovery in primary HIV infection.......BACKGROUND: Symptomatic primary HIV infection is associated with an adverse prognosis, and immediate initiation of combination antiretroviral therapy (cART) is recommended. However, little is known about immunological predictors of immune recovery. Thymic Stromal Lymphopoietin (TSLP) is a cytokine...

The docetaxel radiosensitization experience for the treatment of unresectable esophageal cancer

International Nuclear Information System (INIS)

Maruyama, Shoji; Maruyama, Michio; Tanami, Hideaki

2005-01-01

Docetaxel is an increasingly important drug for the treatment of esophageal cancer. The docetaxel radiosensitization has been established in cancer cell lines. The therapeutic response and toxicity of a weekly docetaxel in combination with radiotherapy for unresectable esophageal cancer were examined. Ten patients with locally advanced or metastatic squamous cell esophageal cancer were recruited in the following protocol. The median age was 65.7 years. Patients received radiation in 2 Gy single daily fractions to a total dose of 60 Gy. Docetaxel (10 mg/m 2 ) was administered weekly for 6 consecutive weeks. One patient could not be evaluated. The overall response rate was 77% with 11% complete response (CR) and 66% partial response (PR). Mild grade 2 leukocytes toxicity was observed in 2/10 patients, which enforced the treatment absence for 7-14 days. Grade 2 stomatitis was noted in one patient. No severe grade 3 adverse effects were observed. It is concluded that low-dose docetaxel with radiotherapy is feasible and, a high response rate can be expected. Toxicity is modest, and this protocol may be useful for the outpatients or neoadjuvant chemotherapy. (author)

Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: Two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor β1 (TGF-β1) in age-related thymic involution.

Science.gov (United States)

Tan, Jianxin; Wang, Yajun; Zhang, Nannan; Zhu, Xike

2016-08-01

Age-related thymic involution is characterized by a loss of thymic epithelial cells (TECs) and a concomitant increase in adipocytes, but the mechanisms involved in thymic adipogenesis are still not clear. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been reported to be up-regulated with age in thymic stromal cells in both human and mouse. However, the exact role of TGF-β1 in age-related thymic involution remains to be further elucidated. On the basis of previous findings, we propose a novel hypothesis that TGF-β1 functions a dual role in age-related thymic involution. On one hand, up-regulation of TGF-β1 promotes epithelial to mesenchymal transition (EMT) process in TECs via activating forkhead box protein C2 (FoxC2). On the other hand, TGF-β1 inhibits the transdifferentiation of EMT-derived mesenchymal cells to adipocytes in the thymus. If confirmed, our hypothesis will not only provide further evidence supporting that the transdifferentiation of TECs into pre-adipocytes represents a source of thymic adiposity during age-related thymic involution, but also uncover a unique role of TGF-β1 in the transdifferentiation of TECs into pre-adipocytes. Collectively, the inhibition of TGF-β1 may serve as a strategy to hinder age-related thymic involution or even to restore thymic function in the elderly. © 2016 International Federation for Cell Biology.

Curative resection for locally advanced sigmoid colon cancer using neoadjuvant chemotherapy with FOLFOX plus panitumumab: A case report

Directory of Open Access Journals (Sweden)

Kenji Tomizawa

2017-01-01

Conclusion: To our knowledge, this is the first report of a successful curative resection in a patient with initially unresectable, locally advanced colorectal cancer who was treated with FOLFOX4 combined with panitumumab.

Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling.

Science.gov (United States)

Belharazem, Djeda; Grass, Albert; Paul, Cornelia; Vitacolonna, Mario; Schalke, Berthold; Rieker, Ralf J; Körner, Daniel; Jungebluth, Philipp; Simon-Keller, Katja; Hohenberger, Peter; Roessner, Eric M; Wiebe, Karsten; Gräter, Thomas; Kyriss, Thomas; Ott, German; Geserick, Peter; Leverkus, Martin; Ströbel, Philipp; Marx, Alexander

2017-10-27

The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1 high thymomas and TCs.

Development of donor-derived thymic lymphomas after allogeneic bone marrow transplantation in AKR/J mice

International Nuclear Information System (INIS)

Yasumizu, R.; Hiai, H.; Sugiura, K.

1988-01-01

The transplantation of bone marrow cells from BALB/c (but not C57BL/6 and C3H/HeN) mice was observed to lead to the development of thymic lymphomas (leukemias) in AKR/J mice. Two leukemic cell lines, CAK1.3 and CAK4.4, were established from the primary culture of two thymic lymphoma, and surface phenotypes of these cell lines found to be H-2d and Thy-1.2+, indicating that these lymphoma cells are derived from BALB/c donor bone marrow cells. Further analyses of surface markers revealed that CAK1.3 is L3T4+ Lyt2+ IL2R-, whereas CAK4.4 is L3T4- Lyt2- IL2R+. Both CAK1.3 and CAK4.4 were transplantable into BALB/c but not AKR/J mice, further indicating that these cells are of BALB/c bone marrow donor origin. The cells were found to produce XC+-ecotropic viruses, but xenotropic and mink cell focus-forming viruses were undetectable. Inasmuch as thymic lymphomas are derived from bone marrow cells of leukemia-resistant BALB/c strain of mice under the allogeneic environment of leukemia-prone AKR/J mice, this animal model may serve as a useful tool not only for the analysis of leukemic relapse after bone marrow transplantation but also for elucidation of the mechanism of leukemogenesis

How nonuniform contact profiles of T cell receptors modulate thymic selection outcomes

Science.gov (United States)

Chen, Hanrong; Chakraborty, Arup K.; Kardar, Mehran

2018-03-01

T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies. Past theoretical work cast thymic selection as an extreme value problem and characterized the statistical enrichment or depletion of amino acids in the postselection TCR repertoire, showing how T cells are selected to be able to specifically recognize peptides derived from diverse pathogens yet have limited self-reactivity. Here, we investigate how the diversity of the postselection TCR repertoire is modified when TCRs make nonuniform contacts with peptide-MHC. Specifically, we were motivated by recent experiments showing that amino acids at certain positions of a TCR sequence have large effects on thymic selection outcomes, and crystal structure data that reveal a nonuniform contact profile between a TCR and its peptide-MHC ligand. Using a representative TCR contact profile as an illustration, we show via simulations that the statistical enrichment or depletion of amino acids now varies by position according to the contact profile, and, importantly, it depends on the implementation of nonuniform contacts during thymic selection. We explain these nontrivial results analytically. Our study has implications for understanding the selection forces that shape the functionality of the postselection TCR repertoire.

Photodynamic Therapy in Patients with Advanced Hilar Cholangiocarcinoma: Percutaneous Cholangioscopic Versus Peroral Transpapillary Approach.

Science.gov (United States)

Lee, Tae Yoon; Cheon, Young Koog; Shim, Chan Sup

2016-04-01

This study aimed to compare the clinical outcomes of patients with advanced hilar cholangiocarcinoma (CC) who underwent photodynamic therapy (PDT) with either percutaneous transhepatic cholangioscopy (PTCS) or endoscopic retrograde cholangiopancreatography (ERCP). PDT has been proposed as a promising therapy for treatment of unresectable hilar CC that is resistant to conventional standard treatment. However, few studies have compared the delivery methods of PDT in unresectable hilar CC patients. Thirty-seven adult patients with advanced hilar CC were included in this study. Twenty-four patients treated with PTCS-directed PDT and 13 patients treated with ERCP-directed PDT were analyzed retrospectively. The PTCS- and ERCP-directed PDT groups were comparable with respect to age, gender, health status, pretreatment bilirubin levels, Bismuth type, and hilar CC stage. The length of hospital stay differed significantly (p hilar CC. Lower pre-PDT bilirubin levels were associated with longer survival in all patients.

Concurrent chemoradiation for unresectable pancreatic cancer

International Nuclear Information System (INIS)

Kim, Yong Bae; Seong, Jin Sil; Song, Si Young; Park, Seung Woo; Suh, Chang Ok

2002-01-01

To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. The patients, who were diagnosed by imaging modalities or by explo-laparotomy were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine 1,000 mg/m 2 or Paclitaxel 50 mg/m 2 weekly and oral 5-FU daily. The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months. Survival was analyzed using the Kaplan-Meier method. Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 60 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to; disease progression for 6 (50%), poor performance status for 4 (33.3%), intercurrent disease for 1 (8.3%), and refusal for 1 (8.3%). Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was 59%. The survival rates were 46.7% and 17.0% at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients (19%), while grade III or IV non-hematologic toxicity was shown in 5 patients (12%). Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient

Association between thymic function and allogeneic hematopoietic stem cell transplantation outcome: results of a pediatric study.

Science.gov (United States)

Saglio, Francesco; Cena, Silvia; Berger, Massimo; Quarello, Paola; Boccasavia, Viola; Ferrando, Federica; Pittana, Laura; Bruno, Benedetto; Fagioli, Franca

2015-06-01

Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Chiorean, E. Gabriela, E-mail: gchiorea@uw.edu [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Department of Medicine, University of Washington, Seattle, Washington (United States); Schneider, Bryan P. [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Akisik, Fatih M. [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Perkins, Susan M. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States); Anderson, Stephen [Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana (United States); Johnson, Cynthia S. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States); DeWitt, John [Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana (United States); Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Deluca, Jill [Department of Radiation Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Bu, Guixue [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Shahda, Safi; Loehrer, Patrick J. [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Sandrasegaran, Kumar [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Cardenes, Higinia R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States)

2014-06-01

Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m{sup 2} intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m{sup 2} intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K{sup trans} in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival.

Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

International Nuclear Information System (INIS)

Chiorean, E. Gabriela; Schneider, Bryan P.; Akisik, Fatih M.; Perkins, Susan M.; Anderson, Stephen; Johnson, Cynthia S.; DeWitt, John; Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John; Deluca, Jill; Bu, Guixue; Shahda, Safi; Loehrer, Patrick J.; Sandrasegaran, Kumar; Cardenes, Higinia R.

2014-01-01

Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m 2 intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m 2 intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K trans in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival

Three distinct subsets of thymic epithelial cells in rats and mice defined by novel antibodies.

Directory of Open Access Journals (Sweden)

Yasushi Sawanobori

Full Text Available Thymic epithelial cells (TECs are thought to play an essential role in T cell development and have been detected mainly in mice using lectin binding and antibodies to keratins. Our aim in the present study was to create a precise map of rat TECs using antibodies to putative markers and novel monoclonal antibodies (i.e., ED 18/19/21 and anti-CD205 antibodies and compare it with a map from mouse counterparts and that of rat thymic dendritic cells.Rat TECs were subdivided on the basis of phenotype into three subsets; ED18+ED19+/-keratin 5 (K5+K8+CD205+ class II MHC (MHCII+ cortical TECs (cTECs, ED18+ED21-K5-K8+Ulex europaeus lectin 1 (UEA-1+CD205- medullary TECs (mTEC1s, and ED18+ED21+K5+K8dullUEA-1-CD205- medullary TECs (mTEC2s. Thymic nurse cells were defined in cytosmears as an ED18+ED19+/-K5+K8+ subset of cTECs. mTEC1s preferentially expressed MHCII, claudin-3, claudin-4, and autoimmune regulator (AIRE. Use of ED18 and ED21 antibodies revealed three subsets of TECs in mice as well. We also detected two distinct TEC-free areas in the subcapsular cortex and in the medulla. Rat dendritic cells in the cortex were MHCII+CD103+ but negative for TEC markers, including CD205. Those in the medulla were MHCII+CD103+ and CD205+ cells were found only in the TEC-free area.Both rats and mice have three TEC subsets with similar phenotypes that can be identified using known markers and new monoclonal antibodies. These findings will facilitate further analysis of TEC subsets and DCs and help to define their roles in thymic selection and in pathological states such as autoimmune disorders.

Intrahepatic chemoembolization in unresectable pediatric liver malignancies

International Nuclear Information System (INIS)

Arcement, C.M.; Towbin, R.B.; Meza, M.P.; Kaye, R.D.; Carr, B.I.; Gerber, D.A.; Mazariegos, G.V.; Reyes, J.

2000-01-01

Objective. To determine the effectiveness of a new miltidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy. Materials and methods. From November 1989 to April 1998, 14 children (2-15 years old) were treated with 50 courses of intra-arterial chemotherapy. Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed. Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant). All patients had subselective hepatic angiography and infusion of cisplatin and/or adriamycin (36 courses were followed by gelfoam embolization). The procedure was repeated every 3-4 weeks based on hepatic function and patency of the hepatic artery. Results. Six of 14 children received orthotopic liver transplants (31 courses of IHC). Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size. Three of 6 patients are disease free at this time. Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant. One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx. Three of 14 withdrew from the program and died. Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates. Two hepatic arteries thrombosed, and one child had a small sealed-off gastric ulcer as complications of intrahepatic chemoembolization. Conclusion. The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant. Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response. IHCE does not appear to convert

Intrahepatic chemoembolization in unresectable pediatric liver malignancies

Energy Technology Data Exchange (ETDEWEB)

Arcement, C.M.; Towbin, R.B.; Meza, M.P.; Kaye, R.D.; Carr, B.I. [Department of Radiology, Children' s Hospital of Pittsburgh, PA (United States); Gerber, D.A.; Mazariegos, G.V.; Reyes, J. [Department of Transplant Surgery, Children' s Hospital of Pittsburgh, PA (United States)

2000-11-01

Objective. To determine the effectiveness of a new miltidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy. Materials and methods. From November 1989 to April 1998, 14 children (2-15 years old) were treated with 50 courses of intra-arterial chemotherapy. Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed. Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant). All patients had subselective hepatic angiography and infusion of cisplatin and/or adriamycin (36 courses were followed by gelfoam embolization). The procedure was repeated every 3-4 weeks based on hepatic function and patency of the hepatic artery. Results. Six of 14 children received orthotopic liver transplants (31 courses of IHC). Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size. Three of 6 patients are disease free at this time. Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant. One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx. Three of 14 withdrew from the program and died. Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates. Two hepatic arteries thrombosed, and one child had a small sealed-off gastric ulcer as complications of intrahepatic chemoembolization. Conclusion. The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant. Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response. IHCE does not appear to convert

FDG PET as a prognostic predictor in the early post-therapeutic evaluation for unresectable hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Higashi, Tatsuya; Nishii, Ryuichi [Shiga Medical Center Research Institute, Moriyama City, Shiga (Japan); Hatano, Etsuro; Ikai, Iwao; Seo, Satoru; Kitamura, Koji; Takada, Yasuji; Kamimoto, Shinji [Kyoto University Graduate School of Medicine, Department of Gastroenterological Surgery, Sakyo-ku, Kyoto (Japan); Nakamoto, Yuji; Ishizu, Koichi; Suga, Tsuyoshi; Kawashima, Hidekazu; Togashi, Kaori [Kyoto University Graduate School of Medicine, Department of Diagnostic Imaging and Nuclear Medicine, Sakyo-ku, Kyoto (Japan)

2010-03-15

To elucidate the prognostic role of post-therapeutic {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET), we conducted a retrospective cohort study analysing the clinical factors that affect overall survival after non-operative therapy for unresectable hepatocellular carcinoma (HCC). Sixty-seven cases with unresectable HCC who received non-operative therapy (transcatheter arterial chemoembolization: n=24, transcatheter arterial infusion chemotherapy: n=31, radiofrequency ablation: n = 5 or systemic chemotherapy: n = 7) and had received FDG PET for the evaluation of the therapeutic effect within 1 month after the end of the therapy were evaluated. Overall survival rate was evaluated using the univariate and multivariate analyses of relevant clinical and laboratory parameters before and after therapy, including visual PET analysis and quantitative analysis using maximum standardized uptake value (SUV). Visual PET diagnosis of post-therapeutic lesions was a good predictor of overall survival of unresectable HCC patients. The low FDG group showed significantly longer survival (average: 608 days) than that (average: 328 days) of the high FDG group (p<0.0001). Multivariate analysis showed four significant prognostic factors for the survival: post-therapeutic alpha-fetoprotein ({alpha}FP) level (=400 ng/ml, p=0.004), post-therapeutic visual PET diagnosis (p=0.006), post-therapeutic clinical stage (UICC stage IV, p=0.04) and post-therapeutic Milan criteria (p=0.03), while pre-therapeutic clinical factors, SUV by post-therapeutic FDG PET (5.0 or more) or others did not show significance. The present study suggests that post-therapeutic PET performed within 1 month after non-operative therapy can be a good predictor of overall survival in unresectable HCC patients, while pre-therapeutic evaluation including PET, tumour markers and clinical staging may not be useful. (orig.)

Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

DEFF Research Database (Denmark)

Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette

2002-01-01

In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...

Unusual Thymic Hyperplasia Mimicking Lipomatous Tumor in an Eight-Year-Old Boy with Concomitant Pericardial Lipomatosis and Right Facial Hemihypertrophy

International Nuclear Information System (INIS)

Kim, Yoo Jin; Kim Woo Sun; Cheon, Jung Eun; Lim, Yun Jung; Kim, In One; Yeon, Kyung Mo; Jung, Kyeong Cheon; Byun, Sun Ju

2011-01-01

We report a case of thymic hyperplasia accompanied by pericardial lipomatosis and right facial hemihypertrophy in an 8-year-old boy. On imaging studies, the hyperplastic thymus had prominent curvilinear and nodular fatty areas simulating a fat-containing anterior mediastinal mass, which is an unusual finding in children. To our knowledge, this is the first report on a child with a combination of thymic hyperplasia, pericardial lipomatosis, and right facial hemihypertrophy. The radiologic findings are presented with a brief discussion.

Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection

NARCIS (Netherlands)

Hazenberg, Mette D.; Borleffs, J.C.C.; Otto, S.A.; Cohen Stuart, J.W.T. (James Willem Theodoor); Verschuren, M.C.M. (Martie); Boucher, C.A.B.; Coutinho, R.A.; Lange, Joep M.A.; Rinke de Wit, T.F. (Tobias); Tsegaye, A. (Aster); Dongen, J.J.M. (Jaques) van; Hamann, D. (Dörte); Boer, R.J. de; Miedema, F.

2000-01-01

Recent thymic emigrants can be identified by T cell receptor excision circles (TRECs) formed during T-cell receptor rearrangement. Decreasing numbers of TRECs have been observed with aging and in human immunodeficiency virus (HIV)-1 infected individuals, suggesting for thymic impairment. Here,

Human thymic epithelial cells express functional HLA-DP molecules

DEFF Research Database (Denmark)

Jørgensen, A; Röpke, C; Nielsen, M

1996-01-01

T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN-gamma treatment strongly upregulated the HLA-DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels...

Immunologic competence in adults following thymic irradiation in infancy

International Nuclear Information System (INIS)

Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

1977-01-01

Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis

Immunologic competence in adults following thymic irradiation in infancy

Energy Technology Data Exchange (ETDEWEB)

Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

1977-07-01

Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis.

Genetic analysis of radiation-induced mouse thymic lymphomas

International Nuclear Information System (INIS)

Kominami, R.; Wakabayashi, Y.; Niwa, O.

2003-01-01

Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas

Changes in protein expression in p53 deleted spontaneous thymic lymphomas

DEFF Research Database (Denmark)

Honoré, Bent; Vorum, Henrik; Pedersen, Anders Elm

2004-01-01

with the protein expression in p53+/+ and p53-/- thymocytes. Only a minority (13 proteins) of the quantitatively changed proteins were common for the two thymic lymphoma cell lines, suggesting that the p53 deficiency mainly results in genetic dysfunctions which are individual for a given tumor. Two of the detected...... structure containing motifs of the glyoxalase-bleomycin resistance protein family (MDR) as deduced from the cDNA....

Imatinib for the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumours: systematic review and economic evaluation.

Science.gov (United States)

Wilson, J; Connock, M; Song, F; Yao, G; Fry-Smith, A; Raftery, J; Peake, D

2005-07-01

To assess the clinical and cost-effectiveness of imatinib in the treatment of unresectable and/or metastatic, KIT-positive, gastrointestinal stromal tumours (GISTs), relative to current standard treatments. Electronic databases. As there were no randomised trials that have directly compared imatinib with the current standard treatment in patients with advanced GIST, this review included non-randomised controlled studies, cohort studies, and case series that reported effectiveness results of treatment with imatinib and/or other interventions in patients with advanced GIST. The effectiveness assessment was based on the comparison of results from imatinib trials and results from studies of historical control patients. Economic evaluation was mainly based on an assessment and modification (when judged necessary) of a model submitted by Novartis. Evidence from published uncontrolled trials involving 187 patients, and from abstracts reporting similar uncontrolled trials involving 1700 patients, indicates that approximately 50% of imatinib-treated individuals with advanced GIST experience a dramatic clinical response in terms of at least a 50% reduction in tumour mass. At present, although useful data are accumulating, it is not possible to predict which patients may respond in this way. Fifteen studies where possible GIST patients had been treated with therapies other than imatinib or best supportive care were also identified. All imatinib-treated patients experienced adverse effects, although they were relatively mild. Overall, imatinib was reported to be well tolerated. The most common serious events included unspecified haemorrhage and neutropenia. Skin rash, oedema and periorbital oedema were the common adverse events observed. Patients on the highest dose regimen (1000 mg per day in one trial) may experience dose-limiting drug toxicity. A structured assessment was carried out of the Novartis economic evaluation of imatinib for unresectable and/or metastatic GIST

Local radiotherapy for patients with unresectable hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Won; Lim, Do Hoon; Paik, Seung Woon; Koh, Kwang Cheol; Choi, Moon Seok; Park, Cheol Keun; Yoo, Byung Chul; Lee, Jeong Eun; Kang, Min Kyu; Park, Young Je; Nam, Hee Rim; Ahn, Yong Chan; Huh, Seung Jae

2005-01-01

Purpose: To evaluate the response to local radiotherapy (RT) for unresectable hepatocellular carcinoma (HCC) and to analyze the dose-response relationship and the treatment-related morbidities. Methods and materials: Between 1998 and 2002, 59 patients who were treated with localized RT were evaluated. RT was delivered with a curative intent, and the radiation dose was 30-55 Gy (biologic effective dose of 39.0-70.2 Gy 10 using the α/β ratio of 10 Gy) with 2-3 Gy as a daily dose. The tumor response was evaluated by the change in maximum tumor size on serial CT scans, and the morbidity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. Results: An objective tumor response was achieved in 39 of 59 patients (66.1%) with complete response (CR) in 5 patients and partial response (PR) in 34 patients. More than 50 Gy 10 had a significant response; CR or PR was 72.8% with >50 Gy 10 and 46.7% with ≤50 Gy 10 (p = 0.0299). The 2-year overall survival rate after RT was 27.4% (median survival time: 10 months), and this was affected by the tumor response (p = 0.0640); the 2-year overall survival rate after RT was 50.0% for CR and 21.8% for PR. There was no Grade 3 or 4 acute toxicity, and 3 patients (5.1%) developed gastric or duodenal ulcer. Conclusions: Radiotherapy for unresectable HCC resulted in 66.1% of tumor response with acceptable toxicity, and the radiation dose seems to be a significant prognostic factor in RT response for HCC

Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

Energy Technology Data Exchange (ETDEWEB)

Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Pollock, Bruce E. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Schomberg, Paula J. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Link, Michael J. [Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Stafford, Scott L., E-mail: Stafford.scott@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)

2012-05-01

Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4-56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm{sup 3} (range, 0.7-26.7). The median tumor margin dose was 15 Gy (range, 12-20). The median follow-up was 8.0 years (range, 0.5-15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

International Nuclear Information System (INIS)

Hallemeier, Christopher L.; Pollock, Bruce E.; Schomberg, Paula J.; Link, Michael J.; Brown, Paul D.; Stafford, Scott L.

2012-01-01

Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4–56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm 3 (range, 0.7–26.7). The median tumor margin dose was 15 Gy (range, 12–20). The median follow-up was 8.0 years (range, 0.5–15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

Complicated biallelic inactivation of Pten in radiation-induced mouse thymic lymphomas

Energy Technology Data Exchange (ETDEWEB)

Yamaguchi, Yu [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Takabatake, Takashi; Kakinuma, Shizuko; Amasaki, Yoshiko; Nishimura, Mayumi; Imaoka, Tatsuhiko; Yamauchi, Kazumi; Shang, Yi [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Miyoshi-Imamura, Tomoko [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Genetic Counseling Program, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyou-ku, Tokyo 112-8610 (Japan); Nogawa, Hiroyuki [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Kobayashi, Yoshiro [Department of Biomolecular Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510 (Japan); Shimada, Yoshiya, E-mail: y_shimad@nirsgo.jp [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan)

2010-04-01

Inactivation of the phosphatase and tensin homolog gene (Pten) occurs via multiple tissue-dependent mechanisms including epigenetic silencing, point mutations, insertions, and deletions. Although frequent loss of heterozygosity around the Pten locus and plausible involvement of epigenetic silencing have been reported in radiation-induced thymic lymphomas, the proportion of lymphomas with inactivated Pten and the spectrum of causal aberrations have not been extensively characterized. Here, we assessed the mode of Pten inactivation by comprehensive analysis of the expression and alteration of Pten in 23 radiation-induced thymic lymphomas developed in B6C3F1 mice. We found no evidence for methylation-associated silencing of Pten; rather, complex structural abnormalities comprised of missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions were identified in 8 of 23 lymphomas (35%). Sequencing of deletion breakpoints suggested that aberrant V(D)J recombination and microhomology-mediated rearrangement were responsible for the focal deletions. Seven of the 8 lymphomas had biallelic alterations, and 4 of them did not express Pten protein. These Pten aberrations coincided with downstream Akt phosphorylation. In conclusion, we demonstrate that Pten inactivation is frequently biallelic and is caused by a variety of structural abnormalities (rather than by epigenetic silencing) and is involved in radiation-induced lymphomagenesis.

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

Science.gov (United States)

Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

2014-01-10

The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

Yttrium-90 Radioembolization for Unresectable Standard-chemorefractory Intrahepatic Cholangiocarcinoma: Survival, Efficacy, and Safety Study

Energy Technology Data Exchange (ETDEWEB)

Rafi, Shoaib; Piduru, Sarat M. [Emory University School of Medicine, Division of Interventional Radiology and Image Guided Medicine, Department of Radiology (United States); El-Rayes, Bassel; Kauh, John S. [Emory University School of Medicine, Department of Hematology and Medical Oncology (United States); Kooby, David A.; Sarmiento, Juan M. [Emory University School of Medicine, Department of Surgical Oncology in Surgery (United States); Kim, Hyun S., E-mail: kevin.kim@emory.edu [Emory University School of Medicine, Division of Interventional Radiology and Image Guided Medicine, Department of Radiology (United States)

2013-04-15

To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 {+-} 193 [95 % confidence interval (CI) 374-1130] and 345 {+-} 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 {+-} 190 (95 % CI 78-822) and 345 {+-} 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 {+-} 309 (95 % CI 0-1010) days versus 345 {+-} 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. Y90 radioembolization is effective for unresectable standard-chemorefractory ICC.

{sup 18}F-FDG uptake on PET in primary mediastinal non-thymic neoplasm: A clinicopathological study

Energy Technology Data Exchange (ETDEWEB)

Kaira, Kyoichi, E-mail: kkaira1970@yahoo.co.jp [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Abe, Masato [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakagawa, Kazuo; Ohde, Yasuhisa; Okumura, Takehiro [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Takahashi, Toshiaki; Murakami, Haruyasu; Shukuya, Takehito; Kenmotsu, Hirotsugu; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Hayashi, Isamu [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Oriuchi, Noboru [Department of Diagnostic Radiology and Nuclear medicine, Gunma University Graduate School of Medicine, Showa-machi, Maebashi 371-8511, Gunma (Japan); Endo, Masahiro [Division of Diagnostic Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Kondo, Haruhiko [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakajima, Takashi [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan)

2012-09-15

Background: The usefulness of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography (PET) has been investigated in thymic epithelial tumors. However, little is known about PET imaging of {sup 18}F-FDG in primary non-thymic mediastinal neoplasms. The aim of this study is to explore the clinicopathological significance of {sup 18}F-FDG PET in primary mediastinal (non-thymic) neoplasms. Methods: Twenty-one patients with mediastinal neoplasms who underwent {sup 18}F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1α); hexokinase I; vascular endothelial growth factor (VEGF); microvessels (CD34); epidermal growth factor receptor (EGFR); Akt/mTOR signaling pathway (p-Akt and p-mTOR); cell cycle control (p53). Results: Seventeen of 21 patients were imaged on PET system using {sup 18}F-FDG, but 4 patients with a histology of cyst showed nothing abnormal in PET scans. The histology of the resected tumors was as follows: 6 schwannoma, 3 teratoma, 4 cyst, 3 sarcoma, 1 undifferentiated carcinoma, 1 seminoma, 1 mediastinal goiter, 1 ganglioneuroma, and 1 Hodgkin lymphoma. {sup 18}F-FDG uptake was significantly correlated with Glut1, HIF-1α, EGFR, p-Akt and p-S6K. These biomarkers were highly expressed in schwannoma, teratoma and high grade malignancies, whereas all patients with cyst and ganglioneuroma had no positive expression of these biomarkers. High uptake of {sup 18}F-FDG was significant associated with Glut1, VEGF, EGFR, p-Akt, p-S6K and tumor maximal size. Conclusion: The amount of {sup 18}F-FDG uptake in primary mediastinal non-thymic neoplasms is determined by the presence of glucose metabolism (Glut1), hypoxia (HIF-1α) and upstream components of HIF-1α (EGFR, p-Akt and p-S6K)

A prospective and randomized study of radiotherapy, sequential chemotherapy radiotherapy and concomitant chemo therapy-radiotherapy in unresectable non small cell carcinoma of the lung

Directory of Open Access Journals (Sweden)

Dasgupta Anirban

2006-01-01

Full Text Available Purpose: Treatment of advanced Non small cell lung cancer (NSCLC often produces dismal results. Combination of available treatment modalities has reportedly improved the outcome. A prospectively randomized trial was conducted, comparing combined treatment modalities versus radiotherapy alone, in treatment of unresectable NSCLC. Materials and Methods: A total of 103 patients were randomized to three groups. In group ′A′, 32 patients received radiotherapy alone (6500 cGy/30 fraction. In group ′B′, 35 patients received neoadjuvant chemotherapy (Cisplatin 80 mg/m2 on day 1 and Etoposide 100 mg/m day 1-3 intravenously q3 weeks for 3 cycles, followed by radiotherapy (6000 cGy/30 fractions and 3 more cycles of Chemotherapy, with the same regimen. In group ′C′, 36 patients received radiotherapy (5000 cGy/25 fractions with concurrent chemotherapy (ciplatin 20 mg/m2 + Etoposide 75 mg/m2 intravenously on day 1-5 and day 22-26, followed by 2 more cycles of chemotherapy,q3 weeks with the same regimen. Results: Initial treatment responses were significantly higher in group ′B′ ( P P Conclusion: Addition of chemotherapy with radiation in unresectable NSCLC improves response rates, time to tumour progression and disease free survival, though the same effect is not translated in overall survival.

Unresectable liver metastases in colorectal cancer: review of current strategies.

Science.gov (United States)

Sueur, Benjamin; Pellerin, Olivier; Voron, Thibault; Pointet, Anne L; Taieb, Julien; Pernot, Simon

2016-12-01

The objective of the treatment of colorectal cancer patients with unresectable liver metastases should be clearly defined at the outset. Potentially resectable patients should be distinguished from clearly unresectable patients. In defining resectability, it is important to take into account both anatomic characteristics and patient characteristic (comorbidities, symptoms, age). According to this evaluation, treatment should be tailored to each patient. The most widely accepted standard is doublet cytotoxic regimen plus biotherapy (anti-EGFR or anti-VEGF antibodies according to RAS status, but some patients could benefit from an intensified regimen, as triplet chemotherapy ± bevacizumab, or intraarterial treatments (hepatic arterial infusion, radioembolization or chemoembolization), in order to allow resectability. It is therefore very important to discuss the treatments with a multidisciplinary team, including an experienced surgeon, an interventional radiologist and an oncologist. On the other hand, some patients could benefit in terms of quality of life and decreased toxicity from less intense treatment when resection is not an objective. First-line monotherapy or a maintenance strategy with biotherapy and/or cytotoxics could be discussed with these patients, and treatment holidays should be considered in selected patients. Finally, in patients with secondary resection of liver metastases, specificity should be considered in choosing the best adjuvant treatment, such as response to preoperative treatment and individual risk of relapse, which many in some cases justify intensification with hepatic arterial infusion in an adjuvant setting.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

Energy Technology Data Exchange (ETDEWEB)

Pacella, Claudio M. [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)], E-mail: claudiomaurizio.pacella@fastwebnet.it; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)

2008-04-15

Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

International Nuclear Information System (INIS)

Pacella, Claudio M.; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico

2008-01-01

Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival

Postoperative Radiation Therapy for Non-Small Cell Lung Cancer and Thymic Malignancies

International Nuclear Information System (INIS)

Gomez, Daniel R.; Komaki, Ritsuko

2012-01-01

For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC) as well as thymic malignancies. The indications, radiation doses, and treatment fields vary amongst subtypes of thoracic tumors, as does the level of data supporting the use of radiation. For example, in the setting of NSCLC, postoperative radiation is typically reserved for close/positive margins or N2/N3 disease, although such diseases as superior sulcus tumors present unique cases in which the role of neoadjuvant vs. adjuvant treatment is still being elucidated. In contrast, for thymic malignancies, postoperative radiation therapy is often used for initially resected Masaoka stage III or higher disease, with its use for stage II disease remaining controversial. This review provides an overview of postoperative radiation therapy for thoracic tumors, with a separate focus on superior sulcus tumors and thymoma, including a discussion of acceptable radiation approaches and an assessment of the current controversies involved in its use

Inferior Vena Cava and Renal Vein Thrombosis Associated with Thymic Carcinoma

Directory of Open Access Journals (Sweden)

Vlad Teodor Berbecar

2017-01-01

Full Text Available Thymic tumors are rare mediastinal tumors that can present with a wide variety of symptoms. They can cause distant manifestations and are frequently associated with paraneoplastic syndromes. In our case, we describe the evolution of a 68-year-old male whose first manifestation was thrombosis of the inferior vena cava and renal veins. Thrombosis of large abdominal veins is rare, especially without being associated with any other comorbidity or risk factors.

Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer.

Science.gov (United States)

Zhu, Jun; Zhang, Hai-Ping; Jiang, Sen; Ni, Jian

2017-08-01

We investigated the effects of neoadjuvant chemotherapy administered via bronchial arterial infusion (BAI) on unresectable stage III lung squamous cell carcinoma (SCC). This was a single-arm retrospective study of chemotherapy with gemcitabine plus cisplatin (GP) administered via BAI to patients with unresectable lung SCC. Data regarding the post-treatment response rate, downstage rate, and surgery rate, as well as progression-free survival (PFS), overall survival (OS), quality of life, and post-BAI side effects were collected. A total of 36 patients were enrolled in this study between August 2010 and May 2014. The response rate was 72.2%, and the downstage rate was 22.2%. Among the patients who were downstaged, 16 (44.4%) patients were because of their T stage, and 5 (13.9%) patients were downstaged due to to their N stage. The surgery rate was 52.8%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 52.1%. The median PFS was 14.0 months [95% confidence interval (CI): 8.6-19.4], and the median OS was 25.0 months (95% CI: 19.1-30.9). The quality of life was significantly improved, and the chemotherapy was well tolerated. Compared with intravenous neoadjuvant chemotherapy, BAI chemotherapy significantly improved the surgery rate, prolonged PFS and OS, and improved the quality of life in patients with unresectable stage III lung SCC.

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

Science.gov (United States)

Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma

Directory of Open Access Journals (Sweden)

Michelle S. Boyar

2008-01-01

Full Text Available We assessed the efficacy of combined temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma in a phase II single-institution trial. Twenty-four patients were enrolled. Temozolomide (150 mg/m2/day for 7 days every other week was administered with concomitant thalidomide (200 mg/day, and continued until unacceptable toxicity or disease progression. There were no complete responses and two (10% partial responses. Five patients (24% had stable disease for at least six months. Fourteen patients (67% progressed after a median of two-month treatment. The median overall survival (twenty-two assessable patients was 9.5 months [95% CI 7–28 months]. There were no treatment-related deaths or CTC grade 4 toxicities. Thirteen patients were dose-reduced or discontinued thalidomide due to toxicity. In conclusion, this combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with advanced leiomyosarcoma. We hypothesize that temozolomide is the active agent in this regimen, and should be further studied.

Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression

DEFF Research Database (Denmark)

Jin, Xin; Nowell, Craig S; Ulyanchenko, Svetlana

2014-01-01

does not require FOXN1. Here, we have used a revertible severely hypomorphic allele of Foxn1, Foxn1R, to test the stability of the common TEPC in vivo. By reactivating Foxn1 expression postnatally in Foxn1R/- mice we demonstrate that functional TEPCs can persist in the thymic rudiment until at least 6...... months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression, suggesting that manipulation of FOXN1 activity may prove...... a valuable method for long term maintenance of TEPC in vitro....

Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

DEFF Research Database (Denmark)

Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette

2002-01-01

) repertoire were determined. The study demonstrated no correlation between the 2 scanning methods (r = 0.201, p = 0.358 in patients and r = 0.457, p = 0.184 in controls). Among the patients, no association was found between the sonographically estimated thymic size and immunological parameters such as CD4...... count (r = 0.083, p = 0.706), naive CD4 count (r = 0.067, p = 0.762), CD4 + TREC frequency (r = 0.028, p = 0.900) and CD4 + TCR repertoire (r = -0.057, p = 0.828). These findings show that CT remains superior for assessing thymic size in adults and is preferable to ultrasound when evaluating...

Molecular characterization of non-thymic lymphomas in mice exposed to continuous low-dose-rate g-ray irradiation

International Nuclear Information System (INIS)

Takabatake, T.; Fujikawa, K.; Nakamura, S.; Tanaka, S.; Tanaka, I.; Tanaka-Braga III, I.; Sunaga, Y.; Ichinoche, K.; Sato, F.; Tanaka, K.; Matsumoto, T.

2004-01-01

To investigate the effects of continuous low-dose-rate irradiation on life span and neoplasm incidence, SPE B6C3 F1 mice were irradiated with 137Cs-ray at dose-rates of 20, 1 and 0.05 mGy/day with accumulated doses equivalent to 8000, 40 and 20 mGy, respectively. Examination of a total of 3,000 irradiated and 1,000 non-irradiated control mice showed that the life spans of the both sexes irradiated at 20 mGy/day, respectively. Examination of a total of 3,000 irradiated and 1,000 non-irradiated control mice showed that the life spans of the both sexes irradiated at 20 mGy/day were significantly shorter than that of the non-irradiated group. No significant difference in the cause of death and mortality rates was found between the groups. However, non-thymic lymphomas, the most common lethal neoplasm, showed a tendency to develop at an earlier age in mice irradiated with 20 mGy/day, regardless of sex. to obtain clues on the molecular mechanisms underlying the earlier development of non-thymic lymphomas in 20 mGy/day irradiated group, detailed molecular characterizations of non-thymic lymphomas with respect to B-cell or T-cell origin was done by detecting rearrangements in immunoglobulin heavy gene and in T-cell receptor b-and g chain genes by Southem hybridization method. to determine whether the early development of non-thymic lymphomas in 20 mGy/day irradiated group is associated wi the any recurrent chromosomal imbalance such as deletions and amplifications, the genome-wide scanning is also currently in progress by both LOH and array CGH methods. Present data obtained by LOH method show that deletions in parts of chromosomes 11 and 12 were more frequent than in chromosomes 2, 4 and 14 in both the non-irradiated control and 20 mGy/day irradiated groups. this work is supported by grants from Aomori Prefecture, Japan. (Author)

Surgical palliation of unresectable pancreatic head cancer in elderly patients

Science.gov (United States)

Hwang, Sang Il; Kim, Hyung Ook; Son, Byung Ho; Yoo, Chang Hak; Kim, Hungdai; Shin, Jun Ho

2009-01-01

AIM: To determine if surgical biliary bypass would provide improved quality of residual life and safe palliation in elderly patients with unresectable pancreatic head cancer. METHODS: Nineteen patients, 65 years of age or older, were managed with surgical biliary bypass (Group A). These patients were compared with 19 patients under 65 years of age who were managed with surgical biliary bypass (Group B). In addition, the results for group A were compared with those obtained from 17 patients, 65 years of age or older (Group C), who received percutaneous transhepatic biliary drainage to evaluate the quality of residual life. RESULTS: Five patients (26.0%) in Group A had complications, including one intraabdominal abscess, one pulmonary atelectasis, and three wound infections. One death (5.3%) occurred on postoperative day 3. With respect to morbidity, mortality, and postoperative hospitalization, no statistically significant difference was noted between Groups A and B. The number of readmissions and the rate of recurrent jaundice were lower in Group A than in Group C, to a statistically significant degree (P = 0.019, P = 0.029, respectively). The median hospital-free survival period and the median overall survival were also significantly longer in Group A (P = 0.001 and P < 0.001, respectively). CONCLUSION: Surgical palliation does not increase the morbidity or mortality rates, but it does increase the survival rate and improve the quality of life in elderly patients with unresectable pancreatic head cancer. PMID:19248198

The effect of early measles vaccination on thymic size. A randomized study from Guinea-Bissau

DEFF Research Database (Denmark)

Christensen, Lone Damkjær; Eriksen, Helle Brander; Biering-Sørensen, Sofie

2014-01-01

In low-income countries early measles vaccine (MV) is associated with reduced child mortality which cannot be explained by prevention of measles. A large thymus gland in infancy is also associated with reduced mortality. We hypothesized that early MV is associated with increased thymic size. Within...

Identification of differentially expressed proteins in spontaneous thymic lymphomas from knockout mice with deletion of p53

DEFF Research Database (Denmark)

Honoré, Bent; Buus, Søren; Claësson, Mogens H

2008-01-01

ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two-dimensiona......ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two...... alpha type 3, transforming acidic coiled-coil containing protein 3, mitochondrial ornithine aminotransferase and epidermal fatty acid binding protein and down-regulation of adenylosuccinate synthetase, tubulin beta-3 chain, a 25 kDa actin fragment, proteasome subunit beta type 9, cofilin-1 and glia...

Concomitant bid radiotherapy with cisplatin and 5-fluorouracil in unresectable carcinoma of the pharynx: 10 year's experience at the Centre Antoine Lacassagne

International Nuclear Information System (INIS)

Magne, N.; Pivot, X.; Marcy, P.Y.; Chauvel, P.; Courdi, A.; Dassonville, O.; Possonnet, G.; Vallicioni, J.; Ettore, F.; Falewee, M.N.; Milano, G.; Santini, J.; Lagrange, J.L.; Schneider, M.; Demard, F.; Bensadoun, R.J.

2001-01-01

Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors. From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal internal between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21 -day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m 2 (day 1) and 5-FU was given as 6-day continuous infusion (750 mg/m 2 /day at 1. course; 430 mg/m 2 /day at 2. and 3. courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy. Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 3 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall were the Karnofsky index (71% survival at 3 years for patients

Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+ T cell counts and T cell receptor rearrangement excision circles

DEFF Research Database (Denmark)

Lima, K; Abrahamsen, Gitte Meldgaard; Foelling, I

2010-01-01

Thymic hypoplasia is a frequent feature of the 22q11.2 deletion syndrome, but we know little about patients' age-related thymic output and long-term consequences for their immune system. We measured the expression of T cell receptor rearrangement excision circles (TREC) and used flow cytometry...

18F-fluorodeoxyglucose positron tomography is useful in evaluating the efficacy of multidisciplinary treatments for so-called borderline unresectable pancreatic head cancers

International Nuclear Information System (INIS)

Murakami, Makoto; Katayama, Kanji; Yamaguchi, Akio; Iida, Atsushi; Goi, Takanori; Hirono, Yasuo; Nagano, Hideki; Koneri, Kenji

2011-01-01

Currently, computed tomography (CT) is widely used to evaluate the efficacy of treatments on tumor regression in unresectable pancreatic head carcinomas. Recently, 18 F-fluorodeoxyglucose positron emission tomography (PET) examination has been used for the initial diagnosis of pancreatic tumors, for diagnosis of distant metastasis, and for recurrences of pancreatic carcinomas. PET has also been used for the qualitative diagnosis of existing tumors. The current study was designed to observe if PET examination can be used to gauge the efficacy of multidisciplinary treatments, and to estimate the prognosis for unresectable pancreatic head carcinomas in similar clinical stages and during therapy. This was a prospective cohort study and included 18 cases. All cases were unresectable pancreatic head cancers diagnosed as TNM classification stage 3, and had undergone identical multidisciplinary treatment regimens. The level of tumor markers, tumor-size reduction, and maximum standardized uptake values (SUV max ) were correlated with prognosis. Pearson's correlation and Kaplan-Meyer survival rate curves were used for statistical analysis. Tumor-size reduction in CTs and the transition of tumor markers were not related to patient prognosis. Cases in which post-treatment SUV max values were reduced to <3.0 were correlated with a more favorable prognosis and demonstrated extended survival rates. PET examination can be used to estimate the prognosis of unresectable pancreatic head carcinomas which have undergone multidisciplinary treatments. (author)

Cell-intrinsic role for NF-kappa B-inducing kinase in peripheral maintenance but not thymic development of Foxp3+ regulatory T cells in mice.

Directory of Open Access Journals (Sweden)

Susan E Murray

Full Text Available NF-κB inducing kinase (NIK, MAP3K14 is a key signaling molecule in non-canonical NF-κB activation, and NIK deficient mice have been instrumental in deciphering the immunologic role of this pathway. Global ablation of NIK prevents lymph node development, impairs thymic stromal development, and drastically reduces B cells. Despite altered thymic selection, T cell numbers are near normal in NIK deficient mice. The exception is CD4(+ regulatory T cells (Tregs, which are reduced in the thymus and periphery. Defects in thymic stroma are known to contribute to impaired Treg generation, but whether NIK also plays a cell intrinsic role in Tregs is unknown. Here, we compared intact mice with single and mixed BM chimeric mice to assess the intrinsic role of NIK in Treg generation and maintenance. We found that while NIK expression in stromal cells suffices for normal thymic Treg development, NIK is required cell-intrinsically to maintain peripheral Tregs. In addition, we unexpectedly discovered a cell-intrinsic role for NIK in memory phenotype conventional T cells that is masked in intact mice, but revealed in BM chimeras. These results demonstrate a novel role for NIK in peripheral regulatory and memory phenotype T cell homeostasis.

S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling

Science.gov (United States)

Kumar, Ashok; Zamora-Pineda, Jesus; Degagné, Emilie

2017-01-01

Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC). Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes. PMID:29333002

S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling

Directory of Open Access Journals (Sweden)

Ashok Kumar

2017-01-01

Full Text Available Sphingosine-1-phosphate (S1P is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL. SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC. Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes.

Hematological alterations and thymic function in newborns of HIV-infected mothers receiving antiretroviral drugs.

Science.gov (United States)

Wongnoi, Rotjanee; Penvieng, Nawaporn; Singboottra, Panthong; Kingkeow, Doungnapa; Oberdorfer, Peninnah; Sirivatanapa, Pannee; Pornprasert, Sakorn

2013-06-08

To investigate the effects of antiretroviral (ARV) drugs on hematological parameters and thymic function in HIV-uninfected newborns of HIV-infected mothers. Cross sectional study. Chiang-Mai University Hospital, Chiang-Mai, Thailand. 49 HIV-uninfected and 26 HIV-infected pregnancies. Cord blood samples of newborns from HIV-uninfected and HIV-infected mothers were collected. Hematological parameters were measured using automatic blood cell count. T-cell receptor excision circles (TRECs) levels in cord blood mononuclear cells (CBMCs), CD4+ and CD8+ T-cells were quantified using real-time PCR.. Hemotological parameters and thymic function. Newborn of HIV-infected mother tended to have lower mean levels of hemoglobin than those of HIV-uninfected mother (137 ±22 vs 146 ±17 g/L, P = 0.05). Furthermore, mean of red blood cell (RBC) counts and hematocrit and median of TRECs in CD4+ T-cells in the newborns of the former were significantly lower than those of the latter [3.6 ±0.7 vs 4.8 ±0.6 x 1012 cells/L, P cells) in HIV-uninfected newborns of HIV-infected mothers.

Cellular and biochemical actions of adrenal glucocorticoid hormones on rat thymic lymphocytes.

OpenAIRE

Young, D A; Voris, B P; Nicholson, M L

1981-01-01

The molecular, biochemical, and cellular effects of adrenal glucocorticoid hormones on thymic lymphocytes are reviewed, with emphasis on their relationship to the growth suppressive and lethal actions that occur in lymphoid tissues when glucocorticoids are administered to the whole animal. The data support the hypothesis that the hormonal inhibition of growth and development is a consequence of its ability to suppress cellular energy production, causing the cells to behave as though they were...

Treatment results and prognostic indicators in thymic epithelial tumors: a clinicopathological analysis of 45 patients.

Science.gov (United States)

Ansari, Mansour; Dehsara, Farzin; Mohammadianpanah, Mohammad; Mosalaei, Ahmad; Omidvari, Shapour; Ahmadloo, Niloofar

2014-07-01

Thymomas are rare epithelial tumors arising from thymus gland. This study aims at investigating the clinical presentation, prognostic factors and treatment outcome of forty five patients with thymoma and thymic carcinoma. Forty-five patients being histologically diagnosed with thymoma or thymic carcinoma that were treated and followed-up at a tertiary academic hospital during January 1987 and December 2008 were selected for the present study. Twelve patients were solely treated with surgery, 14 with surgery followed by adjuvant radiotherapy, 12 with sequential combined treatment of surgery, radiotherapy and/or chemotherapy and 7 with non-surgical approach including radiotherapy and/or chemotherapy.  Tumors were classified based on the new World Health Organization (WHO) histological classification. There were 18 women and 27 men with a median age of 43 years. Twelve patients (26.7%) had stage I, 7 (17.8%) had stage II, 23 (51%) had stage III and 2 (4.5%) had stage IV disease. Tumors types were categorized as type A (n=4), type AB (n=10), type B1 (n=9), type B2 (n=10), type B3 (n=5) and type C (n=7). In univariate analysis for overall survival, disease stage (P=0.001), tumor size (P=0.017) and the extent of surgical resection (P<0.001) were prognostic factors. Regarding the multivariate analysis, only the extent of the surgical resection (P<0.001) was the independent prognostic factor and non-surgical treatment had a negative influence on the survival. The 5-year and 10-year overall survival rates were 70.8% and 62.9%, respectively. Complete surgical resection is the most important prognostic factor in patients with thymic epithelial tumors.

Cyclosporine promotes the induction of thymic lymphomas in C57BL/6 mice initiated by a single dose of γ-radiation

International Nuclear Information System (INIS)

Yabu, Koji; Warty, V.S.; Gorelik, E.; Shinozuka, Hisashi

1991-01-01

We previously demonstrated that a single dose of γ-radiation (350 rads) was able to induce thymic lymphomas in C57BL mice when followed by promoting treatment with oral cyclosporine (CsA), a non-genotoxic immunosuppressant. We have now tested the efficacy of various doses of γ-radiation as an initiator of CsA promotion of the induction of thymic lymphomas in male C57BL mice. The effects of oral CsA on the splenic natural killer (NK) cell activity of non-irradiated and irradiated (400 rads, 1X) mice were tested by the standard 51 Cr release assays against YAC-1 cells. The cumulative incidence of thymic lymphomas induced by a single dose of γ-radiation at 100, 200, 400 and 600 rads were 10, 25, 63 and 75% respectively, after 42 weeks of CsA promotion. The splenic NK cell activity in non-irradiated mice given CsA for 4 weeks was twice as high as that in the control mice. CsA inhibited poly I:C-induced augmentation of the splenic NK cell activity. In mice given a single dose (400 rads) of γ-radiation and CsA for 4 weeks, a similar but reduced enhancement of the splenic NK cell activity as seen in non-irradiated mice was observed. These results indicate that the efficacy of CsA promotion in the induction of thymic lymphomas is dependent on the initiating doses of γ-radiation, and that CsA enhances host splenic NK cell activity during the early stage of tumor promotion. (author)

Osseous oligometastases from thymic carcinoma: a case report suggesting the effectiveness of palliative-intent radiotherapy treatment.

Science.gov (United States)

Kashima, Jumpei; Horio, Hirotoshi; Okuma, Yusuke; Hosomi, Yukio; Hishima, Tsunekazu

2016-01-01

Oligometastasis, a recently proposed concept, is defined as an intermediate state of cancer, between localized and systemic disease, that may be well controlled by local ablative treatment. Thymic carcinoma is a rare cancer with a poor prognosis. A definitive management approach has yet to be confirmed by a high level of evidence. We present the case of a 41-year-old female who underwent curative-intent surgery for a stage III squamous cell carcinoma of the thymus. Bone metastases were detected 1 year later by magnetic resonance imaging. These were treated with palliative-intent radiotherapy. Disease progression has not been observed in more than 15 years since the achievement of complete radiological remission. The treatment outcomes in this and other reported cases suggest that some patients with oligometastatic thymic carcinoma may achieve prolonged survival or even cure with low-dose radiotherapy delivered to the metastases.

Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

Energy Technology Data Exchange (ETDEWEB)

Mosier, D.E.; Mond, J.J.; Goldings, E.A.

1977-12-01

The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other.

Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

International Nuclear Information System (INIS)

Mosier, D.E.; Mond, J.J.; Goldings, E.A.

1977-01-01

The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other

Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood.

Science.gov (United States)

Duggal, Niharika Arora; Pollock, Ross D; Lazarus, Norman R; Harridge, Stephen; Lord, Janet M

2018-04-01

It is widely accepted that aging is accompanied by remodelling of the immune system including thymic atrophy and increased frequency of senescent T cells, leading to immune compromise. However, physical activity, which influences immunity but declines dramatically with age, is not considered in this literature. We assessed immune profiles in 125 adults (55-79 years) who had maintained a high level of physical activity (cycling) for much of their adult lives, 75 age-matched older adults and 55 young adults not involved in regular exercise. The frequency of naïve T cells and recent thymic emigrants (RTE) were both higher in cyclists compared with inactive elders, and RTE frequency in cyclists was no different to young adults. Compared with their less active counterparts, the cyclists had significantly higher serum levels of the thymoprotective cytokine IL-7 and lower IL-6, which promotes thymic atrophy. Cyclists also showed additional evidence of reduced immunesenescence, namely lower Th17 polarization and higher B regulatory cell frequency than inactive elders. Physical activity did not protect against all aspects of immunesenescence: CD28 -ve CD57 +ve senescent CD8 T-cell frequency did not differ between cyclists and inactive elders. We conclude that many features of immunesenescence may be driven by reduced physical activity with age. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Cryotherapy of employing Argon/Helium assisted with TACE in treating unresectable primary liver carcinoma

International Nuclear Information System (INIS)

Zhang Zhiliang; Yang Xuedong; Cao Yongwei; Lin Xiangyang; Zhang Yongping; Liu Yayuan

2004-01-01

Objective: To investigate the effect of cryotherapy of employing Argon/Helium assisted with TACE for the unresectable primary liver carcinoma. Methods: 124 cases with primary liver carcinoma were randomly divided into two groups: 60 cases were treated by TACE and cryotherapy; the other 64 cases were simply done by TACE as control. In general, TACE was undertaken once a month and altogether three times for a course. Cryotherapy was undergone 1-3 times for a course. Results: The total effective rates (CR + PR) were 45.3% for the control group and 68.3% for the combined therapy group, with an obvious difference between the two groups, 0.5, 1, 1.5 years survival rate were 81.3%, 62.5%, 43.8% respectively in the control group; 93.3%, 83.3%, 63.3% respectively for the combined group. There was an obvious difference between the two groups of 1, 1.5 years of survival rates. Conclusions: Cryotherapy of employing Argon/Helium assisted with TACE for the unresectable primary liver carcinoma is feasible with raising the effective rate and prolonging survival time. (authors)

Diagnostic value of plain chest roentgenogram and CT scan findings in four cases of massive thymic hyperplasia

International Nuclear Information System (INIS)

Kobayashi, T.; Hirabayashi, Y.; Kobayashi, Y.

1986-01-01

Massive thymic hyperplasia (MTH) is rare in the pediatric age group, especially in infants. However, because of a wide variation in size and weight of the thymus, an enlarged gland is often resected because of suspicion of a neoplasm or a cyst. Some cases of thymoma resembling pulmonary acute infection occur less frequently than MTH, but if respiratory problems are accompanied by a large thymus immediate diagnosis is often necessary to differentiate between these two conditions. Four infants (14 days to 4 months of age) with MTH were recently studied, all having an acute onset an of severe respiratory distress. The infants were referred to our center with a tentative diagnosis of thymic or other intrathoracic tumors. The following case reports illustrate our diagnostic approach to evaluate patients with symptoms suggesting MTH and the response to the ''steroid test''. (orig.)

Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC

DEFF Research Database (Denmark)

Schytte, Tine; Hansen, Olfred; Stohlberg-Rohr, Thomine

2010-01-01

    Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity   Backgro......    Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity......   Background: Lung and oesophageal toxicity have been regarded as main toxicity in definitive radiotherapy (RT) of non-small cell lung cancer (NSCLC), whereas cardiac toxicity has not been offered much concern. This is probably due to the poor prognosis for patients with unresectable NSCLC. In this study we...

The prognostic value of the systemic inflammatory score in patients with unresectable metastatic colorectal cancer.

Science.gov (United States)

Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Fukuoka, Tatsunari; Matsutani, Shinji; Kimura, Kenjiro; Amano, Ryosuke; Hirakawa, Kosei; Ohira, Masaichi

2018-07-01

Inflammation has been widely recognized as a contributor to cancer progression and several inflammatory markers have been reported as associated with the clinical outcomes in patients with various types of cancer. Recently, a novel inflammatory marker, the systemic inflammatory score (SIS), which is based on a combination of the lymphocyte-to-monocyte ratio (LMR) and the serum albumin concentration has been reported as a useful prognostic marker. The aim of the present study was to assess the prognostic value of the SIS in patients with unresectable metastatic colorectal cancer (mCRC). The retrospective cohort study included 160 patients who underwent combination chemotherapy for unresectable mCRC between January 2008 and December 2016. The SIS was used to classify the patients into three groups based on their LMR and the serum albumin concentration. Patients with high-LMR and high serum albumin level were given a score of 0; patients with low-LMR or low serum albumin level were given a score of 1; patients with low-LMR and low serum albumin level were given a score of 2. There were significant differences in the overall survival among the three SIS groups and the SIS was an independent prognostic factor for the overall survival. Although the SIS was significantly associated with the overall survival rate even when using the original cut-off values, the SIS according to the new cut-off values had a more accurate prognostic value. The present study determined that the SIS was a useful biomarker for predicting the survival outcomes in patients with unresectable mCRC, although the optimum cut-off value of the SIS according to the patients' background needs to be examined in further studies.

Imaging follow-up in patients with unresectable cellular hepatocarcinoma treated with conventional TACE

International Nuclear Information System (INIS)

Dumitru, R.

2012-01-01

Full text: Background: Hepatocellular carcinoma (HCC) represents more than 5% of all neoplasms and is the most frequent cause of mortality in patients with cirrhosis. Although a number of therapeutic options are available, transarterial chemoembolisation is widely used in the treatment of unresectable HCC. Aim: Evaluation of the role of CT and MRI exams in the imaging followup of patients with unresectable hepatocellular carcinoma treated with conventional transarterial chemoembolisation (TACE). Materials and methods: We retrospectively reviewed 120 consecutive patients with the diagnosis of HCC, sent to the Department of Radiology, Medical Imaging and Interventional Radiology between january 2011 and april 2012 for TACE. The diagnosis of HCC was established using imaging criteria and elevated alfafetoprotein levels (higher than 400ng/ml) or histologic diagnosis. After the procedure, the imaging followup algorithm consisted in an ultrasound exam 24 hours after the procedure, a CT exam 1 month, a MRI exam 3 months later (if the previous CT showed no tumoral residues) and a CT exam 6 months later. The tumoral response was evaluated using the modified RECIST criteria (tumoral dimensions defined as the product of the 2 largest diameters), the visualisation of tumoral arterial enhancement and the presence of intratumoral lipiodol accumulation (defined as absent, homogenous or heterogenous). Results: At the CT exam performed 1 month after the procedure, 44 patients (37%) had homogenous intratumoral lipiodol accumulation, without any tumoral residues and with dimensional reduction. In patients with tumoral residue (n=76), the intratumoral lipiodol accumulation was homogenous (n=48) or heterogenous (n=28); in 5 cases, after the first TACE procedure, we had no lipiodol accumulation in the target lesion. Conclusion: CT exam is an essential tool in the postprocedural followup in patients with unresectable hepatocellular carcinoma treated with conventional transarterial

Apoptosis-promoted tumorigenesis: γ-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death

OpenAIRE

Michalak, Ewa M.; Vandenberg, Cassandra J.; Delbridge, Alex R.D.; Wu, Li; Scott, Clare L.; Adams, Jerry M.; Strasser, Andreas

2010-01-01

Although tumor development requires impaired apoptosis, we describe a novel paradigm of apoptosis-dependent tumorigenesis. Because DNA damage triggers apoptosis through p53-mediated induction of BH3-only proteins Puma and Noxa, we explored their roles in γ-radiation-induced thymic lymphomagenesis. Surprisingly, whereas Noxa loss accelerated it, Puma loss ablated tumorigenesis. Tumor suppression by Puma deficiency reflected its protection of leukocytes from γ-irradiation-induced death, because...

Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk

DEFF Research Database (Denmark)

Jeppesen, Dorthe Lisbeth; Hasselbalch, H; Ersbøll, A K

2003-01-01

AIM: To examine the size of the thymus in uninfected infants born to HIV-positive mothers and to study the effects of feeding by human donor milk on the size of the thymus in these infants. METHODS: The absolute and relative thymic size was assessed by sonography as thymic index (Ti), and the Ti....../weight-ratio (Ti/w) at birth and at 4 mo of age in 12 healthy uninfected infants born to HlV-infected mothers. All infants were exclusively fed pasteurized donor milk. The results were compared with those obtained from a previous cohort of exclusively breastfed, partially breastfed and exclusively formula......-fed infants. RESULTS: At birth the Ti was reduced in infants born to HIV-infected mothers in comparison with that in control infants but this difference disappeared when their birthweights were taken into consideration (Ti/w-ratio). At 4 mo of age the geometric mean Ti of infants fed donor milk was 23...

Treatment Outcome Following Transarterial Chemoembolization in Advanced Bone and Soft Tissue Sarcomas

Energy Technology Data Exchange (ETDEWEB)

Jiang, Chunyu; Wang, Jianbo, E-mail: a602131499@163.com [Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Department of Radiology (China); Wang, Yonggang [Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Department of Oncology (China); Zhao, Jungong; Zhu, Yueqi; Ma, Xu; Zhou, Jia [Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Department of Radiology (China); Yan, Xuebing [Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Department of General Surgery (China)

2016-10-15

PurposeTransarterial chemoembolization (TACE) is used to treat unresectable bone and soft tissue sarcoma (STS) and as a pre-surgical adjuvant treatment. However, its efficiency for advanced STS is undetermined. This study evaluated TACE’s efficiency in treating advanced STS and prognostic factors for patient survival.Materials and MethodsWe enrolled 39 patients with unresectable STS who underwent TACE as an alternative treatment during 2010–2014, with overall survival (OS) as the primary end point. Cancer pain was evaluated by visual analogue scores (VAS) before and after TACE procedures. Factors that affect survival were evaluated by multivariate analyses (Cox proportional hazard model).ResultsMean OS after TACE was 23.7 ± 2.1 months, with 1-year OS 71.5 %, 2-year OS 45.8 %, and 3-year OS 32.5 %. Lesion number and tumor stage were key predictors of survival. TACE was found to decrease cancer pain VAS and increase relapse interval. Size of polyvinyl alcohol (PVA) particle diameter (P = 0.03) and imaging response (P = 0.044) were also found to affect relapse interval.ConclusionTACE was an effective treatment for advanced STS, with a 32.5 % 3-year OS rate, and led to lower cancer pain VAS and longer relapse intervals than chemoinfusion only. Smaller PVA particles are preferable during the TACE procedure.

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided versus empirical chemotherapy in unresectable non-small cell lung cancer.

Science.gov (United States)

Moon, Yong Wha; Sohn, Joo Hyuk; Kim, Yong Tai; Chang, Hyun; Jeong, Jae Heon; Lee, Young Joo; Chang, Joon; Kim, Se Kyu; Jung, Minkyu; Hong, Soojung; Choi, Sung Ho; Kim, Joo-Hang

2009-10-01

We retrospectively compared adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided and empirical chemotherapies for unresectable non-small cell lung cancer (NSCLC) in this case-control study. Unresectable NSCLC patients receiving ATP-CRA-guided platinum-based doublets as first-line therapy were enrolled as cases (n=27; 14 platinum-sensitive and 13 platinum-resistant patients). Performance status, stage, and chemotherapeutic regimen-matched patients receiving empirical chemotherapy were selected from the retrospective database as controls (n=93) in a case to control ratio of approximately 1:3. Response rate and survival (progression-free; overall) in both groups were not significantly different. However, the platinum-sensitive subgroup by ATP-CRA showed a higher response rate than the empirical group (71 versus 38%; p=0.023) with a trend toward longer progression-free survival (8.7 versus 4.8 months for platinum-sensitive versus empirical; p=0.223) and overall survival (not reached versus 12.6 months for platinum-sensitive versus empirical for p=0.134). ATP-CRA may be helpful in selecting platinum-responsive patients in unresectable NSCLC. We consider that nonplatinum doublets in platinum-resistant patients by ATP-CRA may be a more adapted approach than platinum-based doublets in future clinical trials.

Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

International Nuclear Information System (INIS)

Longo, D.L.; Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.

1985-01-01

The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

Treatment Results and Prognostic Indicators in Thymic Epithelial Tumors: A Clinicopathological Analysis of 45 Patients

Directory of Open Access Journals (Sweden)

Mansour Ansari

2014-07-01

Full Text Available Background: Thymomas are rare epithelial tumors arising from thymus gland. This study aims at investigating the clinical presentation, prognostic factors and treatment outcome of forty five patients with thymoma and thymic carcinoma. Methods: Forty-five patients being histologically diagnosed with thymoma or thymic carcinoma that were treated and followed-up at a tertiary academic hospital during January 1987 and December 2008 were selected for the present study. Twelve patients were solely treated with surgery, 14 with surgery followed by adjuvant radiotherapy, 12 with sequential combined treatment of surgery, radiotherapy and/or chemotherapy and 7 with non-surgical approach including radiotherapy and/or chemotherapy. Tumors were classified based on the new World Health Organization (WHO histological classification. Results: There were 18 women and 27 men with a median age of 43 years. Twelve patients (26.7% had stage I, 7 (17.8% had stage II, 23 (51% had stage III and 2 (4.5% had stage IV disease. Tumors types were categorized as type A (n=4, type AB (n=10, type B1 (n=9, type B2 (n=10, type B3 (n=5 and type C (n=7. In univariate analysis for overall survival, disease stage (P=0.001, tumor size (P=0.017 and the extent of surgical resection (P<0.001 were prognostic factors. Regarding the multivariate analysis, only the extent of the surgical resection (P<0.001 was the independent prognostic factor and non-surgical treatment had a negative influence on the survival. The 5-year and 10-year overall survival rates were 70.8% and 62.9%, respectively. Conclusion: Complete surgical resection is the most important prognostic factor in patients with thymic epithelial tumors.

Primary thymic extranodal marginal zone B cell lymphoma as an incidental finding in a Caucasian woman

DEFF Research Database (Denmark)

Krogh Petersen, Jeanette; Larsen, Thomas Stauffer; Møller, Michael Boe

2015-01-01

Primary thymic extranodal marginal zone B cell lymphoma (TML) is an extremely rare lymphoma strongly associated with autoimmune disease. We report an exceedingly rare case of TML found in a non-Asian population. TML was found incidentally in a 60-year-old Caucasian woman with a short history...

Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and pathological findings

International Nuclear Information System (INIS)

Pirronti, T.; Rinaldi, P.; Marano, P.; Batocchi, A.P.; Evoli, A.; Di Schino, C.

2002-01-01

Purpose: To achieve a better understanding of the role of CT and MR imaging in the study of the mediastinum in patients with myasthenia gravis (MG). Material and Methods: Mediastinal CT and MR findings were correlated with the histopathological results in 104 thymectomized MG patients. Results: CT was performed in 104 patients; in 11 of them, MR was also carried out. 44 patients had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in 46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77% specificity for thymoma. In 10 patients with invasive thymoma, CT was indiscriminate, while invasiveness was detected in 7 cases at MR (70% sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5 cases, but the exact localization and degree of invasion were best defined by MR. Conclusion: In MG patients CT is a sensitive, specific and efficient modality for detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown to be accurate in detecting invasive thymoma both preoperatively and in postoperative follow-up

Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and pathological findings

Energy Technology Data Exchange (ETDEWEB)

Pirronti, T.; Rinaldi, P.; Marano, P. [Univ. Cattolica del S. Cuore, Roma (Italy). Inst. of Radiology; Batocchi, A.P.; Evoli, A.; Di Schino, C. [Univ. Cattolica del S. Cuore, Roma (Italy). Inst. of Neurology

2002-07-01

Purpose: To achieve a better understanding of the role of CT and MR imaging in the study of the mediastinum in patients with myasthenia gravis (MG). Material and Methods: Mediastinal CT and MR findings were correlated with the histopathological results in 104 thymectomized MG patients. Results: CT was performed in 104 patients; in 11 of them, MR was also carried out. 44 patients had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in 46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77% specificity for thymoma. In 10 patients with invasive thymoma, CT was indiscriminate, while invasiveness was detected in 7 cases at MR (70% sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5 cases, but the exact localization and degree of invasion were best defined by MR. Conclusion: In MG patients CT is a sensitive, specific and efficient modality for detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown to be accurate in detecting invasive thymoma both preoperatively and in postoperative follow-up.

Synergistic action of radiation and chemical carcinogen in induction of thymic lymphoma in mice

International Nuclear Information System (INIS)

Kajitani, Takashi; Kamiya, Kenji; Seyama, Toshio; Ito, Takaaki; Yokoro, Kenjiro

1980-01-01

Young adult C57BL/6 female mice were used to study the induction of leukemia by a combined treatment of x-rays and N-nitrosoethylurea (NEU). Administration of NEU after x-ray irradiation induced the leukemia in 100% with shortening latent period, which indicated that the combined treatment enhanced the leukemia induction. Thymic localized X-irradiation decreased the leukemia induction ratio from 100 to 55% and prolonged the latent period from 86 days to 128 days, compared with the whole body irradiation. For whole body irradiation, thymus weights, cell counts, rates of DNA-synthesizing cells, and rates, of mitotic index were decreased markedly after irradiation. For thymus weights and cell counts minimum values were observed after 3 days, and recovered by 10 days. DNA-synthesizing cells and the rates of mitotic index began to increase from the minimum value at the first day to the maximum value at the 5th day after irradiation. By thymic localized irradiation, no marked damage nor recovering process could be followed. It was suggested that the administration of NEU after irradiation, especially, to the young recovering cells with high potential for proliferation derived the high induction rate of leukemia. (Nakanishi, T.)

Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk.

Science.gov (United States)

Jeppesen, D; Hasselbalch, H; Ersbøll, A K; Heilmann, C; Valerius, N H

2003-06-01

To examine the size of the thymus in uninfected infants born to HIV-positive mothers and to study the effects of feeding by human donor milk on the size of the thymus in these infants. The absolute and relative thymic size was assessed by sonography as thymic index (Ti), and the Ti/weight-ratio (Ti/w) at birth and at 4 mo of age in 12 healthy uninfected infants born to HlV-infected mothers. All infants were exclusively fed pasteurized donor milk. The results were compared with those obtained from a previous cohort of exclusively breastfed, partially breastfed and exclusively formula-fed infants. At birth the Ti was reduced in infants born to HIV-infected mothers in comparison with that in control infants but this difference disappeared when their birthweights were taken into consideration (Ti/w-ratio). At 4 mo of age the geometric mean Ti of infants fed donor milk was 23.8 and the mean Ti/w-ratio was 4.2. Compared with those of exclusively breastfed infants, the Ti and Ti/w-ratio of infants fed donor milk were significantly reduced (p milk-fed infants compared with that in the formula-fed infants (p = 0.02). At birth the size of the thymus was smaller in uninfected infants of HIV-positive mothers compared with infants of HIV-negative mothers but when birthweight was taken into account this difference disappeared. Feeding by human donor milk seemed to result in an increased size of the thymus at 4 mo of age compared with thymic size in infants that were exclusively formula fed.

Clinical application of SPECT-CT with 99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs).

Science.gov (United States)

Sergieva, Sonya; Robev, Bozhil; Dimcheva, Milena; Fakirova, Albena; Hristoskova, Radka

2016-01-01

Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with 99mTc-Tektrotyd for imaging, staging and follow up of patients with bronchial and thymic neuroendocrine tumors. Forty-one patients with thoracic tumors with neuroendocrine differentiation were studied. Sixty-eight examinations including SPECT-CT studies of the neck and chest and/or abdomen and pelvis were carried out 2-4 hrs. post i.v. administration of aver-age 740 MBq activity dose of 99mTc-EDDA/HYNIC-TOC (Tektrotyd, Polatom). In all 41 investigated patients we obtained 81.25% (13/16), 88% (22/25) and 85.36% (35/41) of sensitivity, specificity and accuracy of this diagnostic approach, respectively. Somatostatin-receptor scintigraphy correctly identified all primary NETs located in the lungs and thymus. SPECT-CT studies with 99mTc-EDDA/HYNIC-TOC resulted in exact pre-surgical and pre-treatment N/M staging of bronchial and thymic NETs, except 2 cases with multiple hepatic metastases and 1 with massive suprarenal metastasis. It can be concluded that SPECT-CT with 99mTc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.

Early Relapse of Unresectable Gallbladder Cancer after Discontinuation of Gemcitabine Monotherapy Administered for 5 Years in a Patient Who Had Complete Response to the Treatment

Directory of Open Access Journals (Sweden)

Koichi Suyama

2013-10-01

Full Text Available The tumor shrinkage effect of gemcitabine is considered to be limited in cases of advanced gallbladder cancer, and there are few reports of complete response to gemcitabine therapy in patients with this cancer. Therefore, the treatment continuation strategy in these patients, after a complete response has been achieved, still remains to be established. Here, we present the case of a 77-year-old patient with unresectable gallbladder cancer, who after showing complete response to gemcitabine monotherapy administered for 5 years, showed early relapse within only 11 months of discontinuation of the drug. Thus, it is necessary to establish a suitable treatment continuation strategy for patients who show complete response to gemcitabine treatment.

Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms.

Science.gov (United States)

Feyerabend, Thorsten B; Terszowski, Grzegorz; Tietz, Annette; Blum, Carmen; Luche, Hervé; Gossler, Achim; Gale, Nicholas W; Radtke, Freddy; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2009-01-16

Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion. Single-cell genotyping showed, however, that the majority of these thymic B cells arose from Notch1-sufficient cells by a cell-extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B cells originating from Notch1-deleted pro-T cells. Chimeric mice lacking the Notch ligand delta-like 4 (Dll4) in thymus epithelium revealed an essential role for Dll4 in T cell development. Thus, Notch1-Dll4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus.

Use of Yttrium-90 TheraSphere for the treatment of unresectable hepatocellular carcinoma.

Science.gov (United States)

Liu, Michael D; Uaje, Michelle B; Al-Ghazi, Muthana S; Fields, Denise; Herman, June; Kuo, Jeffrey V; Milne, Norah; Nguyen, Thong H; Ramsinghani, Nilam S; Tokita, Kenneth M; Tsai, Fong Y; Vajgrt, Duane J; Imagawa, David K

2004-11-01

This is a retrospective analysis of a new treatment modality, intra-arterial administration of Yttrium-90 TheraSphere, for unresectable hepatocellular carcinoma (HCC). Patients with HCC not amenable to surgical treatment who had satisfactory physiological function without comorbid disease or significant pulmonary shunting were eligible for treatment. Patients were categorized into complete, partial, or no response based on serum alpha-fetoprotein (AFP) levels and CT or MRI imaging. Fourteen patients were considered candidates for treatment. Three patients were excluded due to significant hepatopulmonary shunting. Eleven patients were treated with TheraSphere. One patient (9%) had a complete response, eight patients (78%) had a partial response, and two patients (18%) showed no response. Partial and complete responders with AFP-associated HCC demonstrated a median decrease in AFP levels of 79 per cent at 73 days. No patients developed liver toxicity nor died due to treatment. Five patients (45%) died of progressive disease at a median of 7 months post-treatment. Six patients (54%) were alive at a median of 11 months (range, 9 to 20 months). Okuda stage 2 and 3 patients showed a median survival of 11 months and 7 months, respectively. Yttrium-90 TheraSphere treatment for unresectable hepatocellular carcinoma is well tolerated and appears to extend survival.

Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma

DEFF Research Database (Denmark)

Ascierto, Paolo A; Del Vecchio, Michele; Robert, Caroline

2017-01-01

of ipilimumab 10 mg/kg versus 3 mg/kg. METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint...

Treatment of multiple unresectable basal cell carcinomas from Gorlin-Goltz syndrome: a case report.

Science.gov (United States)

Ojevwe, Fidelis O; Ojevwe, Cindy D; Zacny, James P; Dudek, Arkadiusz Z; Lin, Amy; Kohlitz, Patrick

2015-03-01

Nevoid basal cell carcinoma syndrome (NBCCS), which is also known by other names, including Gorlin-Goltz syndrome and multiple basal-cell carcinoma (BCC) syndrome, is a rare multi-systemic disease inherited in a dominant autosomal manner with complete penetrance and variable expressivity. The main clinical manifestations include multiple BCCs, odontogenic keratocysts of the jaw, hyperkeratosis of the palms and soles, skeletal abnormalities, intracranial calcifications and facial deformities. A 31-year-old male diagnosed with Gorlin-Goltz syndrome with multiple unresectable facial BCCs was treated with the Hedgehog inhibitor vismodegib. After one month of therapy on vismodegib, there were significant reductions in the size of multiple BCCs on the patient's face. The patient remains on this therapy. Hedgehog pathway inhibition is an effective strategy to treat unresectable BCCs from Gorlin-Goltz syndrome. Although vismodegib shows some promising clinical results in the early phase of its use, there are concerns of possible resistance developing within months. Duration of therapy, role of maintenance treatment and drug modification to reduce resistance need to be explored in future case studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Correlation between melphalan pharmacokinetics and hepatic toxicity following hyperthermic isolated liver perfusion for unresectable metastatic disease.

Science.gov (United States)

Mocellin, Simone; Pilati, Pierluigi; Da Pian, Pierpaolo; Forlin, Marco; Corazzina, Susanna; Rossi, Carlo Riccardo; Innocente, Federico; Ori, Carlo; Casara, Dario; Ujka, Francesca; Nitti, Donato; Lise, Mario

2007-02-01

In the present work, we report on the results of our pilot study of hyperthermic isolated hepatic perfusion (IHP) with melphalan alone for patients with unresectable metastatic liver tumors refractory to conventional treatments, with particular regard to the correlation between pharmacokinetic findings and hepatic toxicity. Inclusion criteria were unresectable liver metastases, hepatic parenchyma replacement unresectable liver metastases underwent IHP. No intraoperative mortality occurred. Treatment-related systemic toxicity was minimal and reversible. Three patients (15%) experienced grade 4 hepatic toxicity and died due to liver failure and subsequent multiorgan failure. Other six patients had significant (grade 3-4) but transitory hepatic toxicity. Complete and partial responses were observed in three and nine out of 17 evaluable patients, respectively (overall response rate = 70%). The pharmacokinetics study showed a 3% mean perfusate-to-plasma drug leakage (range 1-6%). Logistic regression analysis showed that drug concentration in the perfusate circuit, but not preoperative tests, significantly and independently correlated with hepatic toxicity (P = 0.028). Following melphalan-based IHP, objective tumor regression could be observed in a remarkable percentage of patients refractory to standard treatments. However, hepatic toxicity and related mortality were significant. Our findings suggest that drug dosage personalization based on the measurement of drug distribution volumes might minimize

Percutaneous intraductal radiofrequency ablation in the management of unresectable Bismuth types III and IV hilar cholangiocarcinoma.

Science.gov (United States)

Wang, Yu; Cui, Wei; Fan, Wenzhe; Zhang, Yingqiang; Yao, Wang; Huang, Kunbo; Li, Jiaping

2016-08-16

To assess the feasibility and safety of percutaneous intraductal radiofrequency ablation (RFA) for unresectable Bismuth types III and IV hilar cholangiocarcinoma. Percutaneous intraductal RFA combined with metal stent placement was successful in all patients without any technical problems; the technical success rate was 100%. Chemotherapy was administered to two patients. After treatment, serum direct bilirubin levels were notably decreased. Six patients died during the follow-up period. Median stent patency from the time of the first RFA and survival from the time of diagnosis were 100 days (95% confidence interval (CI), 85-115 days) and 5.3 months (95% CI, 2.5-8.1 months), respectively. No acute pancreatitis, bile duct bleeding and perforation, bile leakage, or other severe complications occurred. Four cases of procedure-related cholangitis, three cases of postoperative abdominal pain, and five cases of asymptomatic transient increase in serum amylase were observed. One patient who presented with stent blockage 252 days' post-procedure underwent repeat ablation. Between September 2013 and May 2015, nine patients with unresectable Bismuth types III and IV hilar cholangiocarcinoma who were treated with percutaneous intraductal RFA combined with metal stent placement after the percutaneous transhepatic cholangial drainage were included in the retrospective analysis. Procedure-related complications, stent patency, and survival after treatment were investigated. Percutaneous intraductal RFA combined with metal stent placement is a technically safe and feasible therapeutic option for the palliative treatment of unresectable Bismuth types III and IV hilar cholangiocarcinoma. Its long-term efficacy and safety is promising, but needs further study via randomized and prospective trials that include a greater number of patients.

Inhibitory effects of a polypeptide thymic factor on the development of 7,12-dimethylbenz(a)anthragene-induced mammary adenocarcinoma in female rats

Energy Technology Data Exchange (ETDEWEB)

Anisimov, V.N.; Danetskaya, E.V.; Morozov, V.G.; Khavinson, V.Kh.

1980-01-01

It has come to be recognized that tumor growth is accompanied by inhibition of cellular immunity and the function of the T lymphocytes. Restitution of T lymphocyte function by means of several pharmacologic agents such as levamisole, phenformin, or epithalamin (an epiphyseal factor) has, in a number of cases, been accompanied by growth inhibition of both spontaneous and induced tumors. In addition, the importance of the thymus in the regulation of T lymphocytes and in antitumor immunity has been recognized. Several indicators point to the fact that the thymus contains physiologically active substances which stimulate T cell-dependent immunity and prevent the occurrence of neoplasms. These considerations have led to attempts at isolation of active thymic factors and studies on their effects on the appearance and growth of tumors. Previously, a thymic factor - thymarin - had been isolated which imparted immunocompetence to the T lymphocytes. This factor differs from other thymic preparations, including thymosine, in terms of a number of physicochemical characteristics and is a polypeptide with a molecular weight of 5000. This study is concerned with its effects on tumor development - mammary gland adenocarcinoma induced in animals with a chemical carcinogen.

Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial.

Science.gov (United States)

Ruers, Theo; Van Coevorden, Frits; Punt, Cornelis J A; Pierie, Jean-Pierre E N; Borel-Rinkes, Inne; Ledermann, Jonathan A; Poston, Graeme; Bechstein, Wolf; Lentz, Marie-Ange; Mauer, Murielle; Folprecht, Gunnar; Van Cutsem, Eric; Ducreux, Michel; Nordlinger, Bernard

2017-09-01

Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n  38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases. © The Author 2017. Published by Oxford University Press.

Analysis of early initiating event(s) in radiation-induced thymic lymphomagenesis

International Nuclear Information System (INIS)

Muto, Masahiro; Ying Chen; Kubo, Eiko; Mita, Kazuei

1996-01-01

Since the T cell receptor rearrangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of γ T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen-2 + (TL-2 + ) thymocytes. Limited numbers of TL-2 + cells from individual irradiated B10.Thy-1.1 mice were injected into B10.Thy-1.2 mice intrathymically, and the common genetic changes among the donor-type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, but there was no common mutation among the donor-type lymphomas from individual irradiated mice, suggesting that these mutations were late-occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F; 10C), t(1A; 13D) or t(6A; XB) among the donor-type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after γ T cell receptor rearrangements, might be important candidates for initiating events. In the donor-type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after γ TCR rearrangements. (author)

Prognosis of external radiotherapy for unresected bile duct carcinoma

International Nuclear Information System (INIS)

Hirokawa, Yutaka; Kashiwado, Kozo; Kashimoto, Kazuki

1991-01-01

Thirty two patients with unresectable bile duct carcinoma were treated with external irradiation. The outcome of these patients was retrospectively analyzed in terms of survival time and prognostic variables. Nine prognostic variables were examined as follows: sex, performance status, age, radiation doses; irradiation fields, the presence or absence of chemotherapy, values of lactic dehydrogenase before the beginning of treatment, total bilirubin values, and hemoglobin values. In all patients, median survival was 7.3 months, and one-year survival time was 34.4%. The most significant prognostic variable was total radiation doses, followed by performance status, total bilirubin values, and irradiation fields. Higher survival rate was associated with 60 Gy or more doses, the combination of UFT chemotherapy, and 4 mg/dl or less of total bilirubin values. (N.K.)

Y-90 microspheres in the treatment of unresectable hepatocellularcarcinoma

International Nuclear Information System (INIS)

Al-Kalbani, A.; Kamel, Y.

2008-01-01

A small percentage of patients with hepatocellular carcinoma (HCC) arecandidates for curative treatment in form of resection or transplantation.There are different treatment options for unresectable HCC-like localablative therapies and recently systemic therapy with Sorafenib. All of thesehave variable response rate and had been proven to improve survival. In thelast few years, there is a growing interest in TheraSphere radioembolization.It consists of yttrium (Y-90) embedded into nonbiodegradeable glassmicrospheres. It is selectively administered by intraarterial hepaticinjection giving high doses of radiation to the tumor and sparing the liverparenchyma. It has been shown to improve survival and used as a bridge totransplantation and to downstage tumors for resection. Therasphere seems tohave favorable safety profile and has been used in patients with portal veinthrombosis with successful outcome. (author)

Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III-IV unresectable head and neck cancer. Results of a randomized phase II study

International Nuclear Information System (INIS)

Takacsi-Nagy, Zoltan; Polgar, Csaba; Major, Tibor; Fodor, Janos; Hitre, Erika; Remenar, Eva; Kasler, Miklos; Oberna, Ferenc; Goedeny, Maria

2015-01-01

Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer. Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone. Response rate, local tumor control (LTC), locoregional tumor control (LRTC), overall survival (OS), progression-free survival (PFS), and toxicity results were assessed. Three patients from the ICT + CRT group did not appear at the first treatment, so a total of 63 patients were evaluated in the study (30 ICT + CRT group and 33 CRT group). Three patients died of febrile neutropenia after ICT. The median follow-up time for surviving patients was 63 months (range 53-82 months). The rate of radiologic complete response was 63 % following ICT + CRT, whereas 70 % after CRT alone. There were no significant differences in the 3-year rates of LTC (56 vs. 57 %), LRTC (42 vs. 50 %), OS (43 vs. 55 %), and PFS (41 vs. 50 %) in the ICT + CRT group and in the CRT group, respectively. The rate of grade 3-4 neutropenia was significantly higher in the ICT + CRT group than in the CRT group (37 and 12 %; p = 0.024). Late toxicity (grade 2 or 3 xerostomia) developed in 59 and 42 % in the ICT + CRT and CRT groups, respectively. The addition of ICT to CRT did not show any advantage in our phase II trial, while the incidence of adverse events increased. The three deaths as a consequence of ICT call attention to the importance of

Thymic lymphocytes. III. Cooperative phenomenon in the proliferation of thymocytes under Con A stimulation.

Science.gov (United States)

Papiernik, M; Jacobson, J B

1986-01-01

In the present paper, the response of thymocytes to Con A is analyzed in terms of a cooperative phenomenon between medullary thymocytes, cortical thymocytes, thymic accessory cells, and interleukin 2. Medullary thymocytes respond spontaneously to Con A and produce IL-2. The addition of exogenously produced IL-2 enhances their proliferation. Small numbers of cortical (PNA+) thymocytes do not respond to Con A, even in the presence of IL-2-containing supernatant. By increasing the number of PNA+ cells per well, sensitivity to Con A and IL-2 appears. This response may be linked either to the increase in a minor PNA+-responding population and/or to the enhanced contamination by medullary thymocytes and macrophages in non-responding PNA+ thymocyte population. In this hypothesis, either the contaminating cells respond by themselves and/or cooperate with PNA+ cells to induce their proliferation. Coculture of non-responding low numbers of PNA+ thymocytes with Con A- and IL-2-containing supernatant in the presence of PNA- cells containing thymic medullary thymocytes and macrophages always produces a higher response than that of each individual population. These results show that a cooperative phenomenon occurs in the cocultures of PNA+ and PNA- thymic cells. We can show using PNA+ and PNA- thymocytes with different Thy 1 alleles, that indeed both PNA+ and populations participate PNA-thymocytes with different Thy 1 alleles, that indeed both PNA+ and PNA- populations participate in the generation of proliferating cells. We can demonstrate, by lysis experiments with monoclonal antibodies and complement that at the end of coculture, most of the proliferating cells are Lyt 1+, and part are Lyt 2+ or L3T4+. We discuss the fact that the phenotype of the cells after activation does not allow us to deduce the phenotype of their precursors. Lysis of Ia+ cells prior to coculture, reduces the level of the proliferative response but does not modify the percentage of cooperation produced

Influence of prognostic groupings and treatment results in the management of unresectable hepatoma: experience with cis-platinum-based chemoradiotherapy in 76 patients

International Nuclear Information System (INIS)

Abrams, Ross A.; Cardinale, Robert M.; Enger, Cheryl; Haulk, Thomas L.; Hurwitz, Herbert; Osterman, Floyd; Sitzmann, James V.

1997-01-01

Purpose: Internationally, hepatoma is a common cause of cancer death. Although the only curative therapy is surgical, most tumors are unresectable and cause death. The value of nonsurgical, antineoplastic therapy for such tumors is controversial. This study was undertaken to extend and confirm promising, but preliminary, treatment observations in the unresectable context. Methods and Materials: From 1988 to 1993, 76 patients with unresectable, biopsy proven, hepatoma underwent uniform pretreatment assessment followed by induction therapy with external beam radiotherapy (21 Gy/7 fractions/10 days) and intravenous Cisplatinum, 50 mg/m 2 . One month later patients began monthly intrahepatic artery Cisplatinum, 50 mg/m 2 . Clinical course and treatment outcomes were correlated with previously published prognostic factors and groupings (Nomura et al., Okuda et al., Stillwagon, et al.). Results: The toxicity of this therapy was modest and nonlimiting. Twenty-four patients (32%) progressed during induction and prior to receiving two cycles of intrahepatic artery Cisplatinum without evidence of benefit. Patients showing this early progression were more likely to be Stillwagon unfavorable than favorable (p = 0.013), Okuda Stage II than Stage I (p = 0.024), and slightly but not statistically more likely to be alpha-fetoprotein positive than alpha-fetoprotein negative (p = 0.098). The overall objective response rate was 43% (38% among AFP positive and 62% among AFP negative patients) (p = 0.15). Although 21 patients had evidence of extra hepatic metastases, survival for these patients did not differ from patients without metastases (p = 0.09) and patients with extra hepatic metastases were just as likely to show intrahepatic response (p = 0.84). Conclusion: The chemoradiotherapy program utilized produced objective response and minimal toxicity. One-third of patients progressed rapidly in spite of treatment. Among the remaining patients, response occurred frequently. This

B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

International Nuclear Information System (INIS)

Reddy, M.M.; Goh, K.; Hempelmann, L.H.

1976-01-01

B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

Directory of Open Access Journals (Sweden)

Neves-dos-Santos Sandra

2010-01-01

Full Text Available Abstract Background We investigated the effects of the signaling molecules, cyclic AMP (cAMP and protein-kinase C (PKC, on gap junctional intercellular communication (GJIC between thymic epithelial cells (TEC. Results Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC. Conclusions Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.

Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Esnaola, Nestor F.; Chaudhary, Uzair B.; O'Brien, Paul; Garrett-Mayer, Elizabeth; Camp, E. Ramsay; Thomas, Melanie B.; Cole, David J.; Montero, Alberto J.; Hoffman, Brenda J.; Romagnuolo, Joseph; Orwat, Kelly P.; Marshall, David T.

2014-01-01

Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved

Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Esnaola, Nestor F. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Chaudhary, Uzair B.; O' Brien, Paul [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Garrett-Mayer, Elizabeth [Division of Biostatistics and Epidemiology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Camp, E. Ramsay [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Thomas, Melanie B. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Cole, David J. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Montero, Alberto J. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Hoffman, Brenda J.; Romagnuolo, Joseph [Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Orwat, Kelly P. [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Marshall, David T., E-mail: marshadt@musc.edu [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States)

2014-03-15

Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.

Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis.

Science.gov (United States)

Xing, Chen; Ma, Ning; Xiao, He; Wang, Xiaoqian; Zheng, Mingke; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Wang, Renxi

2015-03-01

This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4(+) T cells, this population of B cells supported the maintenance of CD4(+)Foxp3(+) Tregs in vitro, in part, via the CD5-CD72 interaction. Mice homozygous for Cd19(Cre) (CD19(-/-)) express B cells with impaired signaling and humoral responses. Strikingly, CD19(-/-) mice produce fewer CD4(+)Foxp3(+) Tregs and a greater percentage of CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Consistent with these results, transfer of thymic CD19(+)CD5(+)CD1d(hi) B cells into CD19(-/-) mice resulted in significantly up-regulated numbers of CD4(+)Foxp3(+) Tregs with a concomitant reduction in CD4(+)CD8(-) and CD4(-)CD8(+) T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19(+)CD5(+)CD1d(hi) B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4(+)Foxp3(+) Tregs and IL-10-producing Bregs. This study suggests that thymic CD19(+)CD5(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis. © Society for Leukocyte Biology.

Very accelerated radiation therapy: preliminary results in locally unresectable head and neck carcinomas

Energy Technology Data Exchange (ETDEWEB)

Bourhis, Jean; Fortin, Andre; Dupuis, Olivier; Domenge, Christian; Lusinchi, Antoine; Marandas, Patrick; Schwaab, Guy; Armand, Jean Pierre; Luboinski, Bernard; Malaise, Edmond; Eschwege, Francois; Wibault, Pierre

1995-06-15

Purpose: To report preliminary results of a very accelerated radiation therapy Phase I/II trial in locally advanced head and squamous cell carcinomas (HNSCC). Methods and Materials: Between 01/92 and 06/93, 35 patients with an unresectable HNSCC were entered in this study. Thirty-two (91%) had Stage IV, and 3 had Stage III disease. The mean nodal diameter, in patients with clinically involved nodes (83%), was 6.3 cm. The median Karnovsky performance status was 70. The treatment consisted of a twice daily schedule (BID) giving 62 Gy in 20 days. Results: In all cases, confluent mucositis was observed, which started about day 15 and resolved within 6 to 10 weeks. Eighty percent of patients had enteral nutritional support. The nasogastric tube or gastrostomy was maintained in these patients for a mean duration of 51.8 days. Eighteen patients (53%) were hospitalized during the course of treatment due to a poor medical status or because they lived far from the center (mean 25 days). Nineteen patients (56%) (some of whom were initially in-patients) were hospitalized posttreatment for toxicity (mean 13 days). Five patients (15%) were never hospitalized. During the follow-up period, 12 local and/or regional failures were observed. The actuarial 18-month loco-regional control rate was 59% (95% confidence interval, 45-73%). Conclusions: The dramatic shortening of radiation therapy compared to conventional schedules in our series of very advanced HNSCC resulted in: (a) severe acute mucosal toxicity, which was manageable but required intensive nutritional support in all cases; and (b) high loco-regional response rates, strongly suggesting that the time factor is likely to be critical for tumor control in this type of cancer.

Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial.

Science.gov (United States)

Tap, William D; Papai, Zsuzsanna; Van Tine, Brian A; Attia, Steven; Ganjoo, Kristen N; Jones, Robin L; Schuetze, Scott; Reed, Damon; Chawla, Sant P; Riedel, Richard F; Krarup-Hansen, Anders; Toulmonde, Maud; Ray-Coquard, Isabelle; Hohenberger, Peter; Grignani, Giovanni; Cranmer, Lee D; Okuno, Scott; Agulnik, Mark; Read, William; Ryan, Christopher W; Alcindor, Thierry; Del Muro, Xavier F Garcia; Budd, G Thomas; Tawbi, Hussein; Pearce, Tillman; Kroll, Stew; Reinke, Denise K; Schöffski, Patrick

2017-08-01

Evofosfamide is a hypoxia-activated prodrug of bromo-isophosphoramide mustard. We aimed to assess the benefit of adding evofosfamide to doxorubicin as first-line therapy for advanced soft-tissue sarcomas. We did this international, open-label, randomised, phase 3, multicentre trial (TH CR-406/SARC021) at 81 academic or community investigational sites in 13 countries. Eligible patients were aged 15 years or older with a diagnosis of an advanced unresectable or metastatic soft-tissue sarcoma, of intermediate or high grade, for which no standard curative therapy was available, an Eastern Cooperative Oncology Group performance status of 0-1, and measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (1:1) to receive doxorubicin alone (75 mg/m 2 via bolus injection administered over 5-20 min or continuous intravenous infusion for 6-96 h on day 1 of every 21-day cycle for up to six cycles) or doxorubicin (given via the same dose procedure) plus evofosfamide (300 mg/m 2 intravenously for 30-60 min on days 1 and 8 of every 21-day cycle for up to six cycles). After six cycles of treatment, patients in the single-drug doxorubicin group were followed up expectantly whereas patients with stable or responsive disease in the combination group were allowed to continue with evofosfamide monotherapy until documented disease progression. A web-based central randomisation with block sizes of two and four was stratified by extent of disease, doxorubicin administration method, and previous systemic therapy. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival, analysed in the intention-to-treat population. Safety analyses were done in all patients who received any amount of study drug. This study was registered with ClinicalTrials.gov, number NCT01440088. Between Sept 26, 2011, and Jan 22, 2014, 640 patients were enrolled and randomly assigned to a treatment group (317 to

Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus.

Directory of Open Access Journals (Sweden)

Jie Dong

Full Text Available After a tightly regulated developmental program in the thymus, "mature" single positive (SP thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+ pre-RTEs, a population of CD4(+ SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+ pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+ pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+ pre-RTEs is independent of MHC class II and Aire molecules.

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis.

Science.gov (United States)

Zhang, Rong-Xin; Ma, Wen-Juan; Gu, Yu-Ting; Zhang, Tian-Qi; Huang, Zhi-Mei; Lu, Zhen-Hai; Gu, Yang-Kui

2017-07-27

It is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients. One hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients. One hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910). This study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

Percutaneous Irreversible Electroporation of Unresectable Hilar Cholangiocarcinoma (Klatskin Tumor): A Case Report

Energy Technology Data Exchange (ETDEWEB)

Melenhorst, Marleen C. A. M., E-mail: m.melenhorst@vumc.nl; Scheffer, Hester J., E-mail: hj.scheffer@vumc.nl; Vroomen, Laurien G. P. H., E-mail: la.vroomen@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands); Kazemier, Geert, E-mail: g.kazemier@vumc.nl; Tol, M. Petrousjka van den, E-mail: mp.vandentol@vumc.nl [VU University Medical Center, Department of Surgery (Netherlands); Meijerink, Martijn R., E-mail: mr.meijerink@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands)

2016-01-15

Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant tumors located near large vessels or bile ducts. The presence of metal objects in the ablation zone, such as Wallstents, is generally considered a contraindication for IRE, because tissue heating due to power conduction may lead to thermal complications. This report describes a 66-year-old female with a Bismuth–Corlette stage IV unresectable cholangiocarcinoma with a metallic Wallstent in the common bile duct, who was safely treated with percutaneous IRE with no signs for relapse 1 year after the procedure.

Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction

Science.gov (United States)

Kim, Jae Yun; Ko, Gyu Bong; Lee, Tae Hoon; Park, Sang-Heum; Lee, Yun Nah; Cho, Young Sin; Jung, Yunho; Chung, Il-Kwun; Choi, Hyun Jong; Cha, Sang-Woo; Moon, Jong Ho; Cho, Young Deok; Kim, Sun-Joo

2017-01-01

Background/Aims Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. Methods A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. Results The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). Conclusions Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs. PMID:28208003

Comparison of post-embolization syndrome in the treatment of patients with unresectable hepatocellular carcinoma: Trans-catheter arterial chemo-embolization versus Yttrium-90 glass microspheres

International Nuclear Information System (INIS)

Goin, J.E.; Roberts, C.A.; Dancey, J.E.; Sickles, C.J.; Leung, D.A.; Soulen, M.C.

2004-01-01

Post-embolization syndrome (PES) occurs in most patients who undergo trans-catheter arterial chemoembolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). Intra-hepatic arterial administration of TheraSphere, yttrium-90 glass microspheres, is an alternative treatment for unresectable HCC that does not require embolization of major vessels and may have a more favorable toxicity profile than TACE. This paper compares the incidence of PES after TACE vs. TheraSphere treatment in unresectable HCC patients. Data for 29 TACE-treated and 34 TheraSphere-treated patients were evaluated for PES. PES toxicities (i.e., nausea, vomiting, fever in the absence of infection, and abdominal pain) were scored according to Southwest Oncology Group (SWOG) toxicity criteria. PES was defined as a total score for the four toxicities of 2 or greater. Survival was defined from the date of treatment to the date of death. TACE patients underwent one to seven treatment procedures; TheraSphere patients underwent one to two treatment procedures. The incidence of PES was 3.8-times (95% confidence interval 1.6-16.3) higher after TACE [20/29(69%)] than after TheraSphere [6/34 (18%)] treatment; this difference was statistically significant (p=.003). Median survival was similar for TheraSphere (N=20; 378 days, CI 209-719) and TACE (N=29; 343 days, CI 217-511) patients. It was concluded that treatment of unresectable HCC with TheraSphere results in a much lower incidence of PES compared to TACE. Since TheraSphere is a pure beta emitter; it can potentially be administered safely on an outpatient basis, and appears to be at least as efficacious as TACE on survival with fewer treatments per patient. (author)

Carbon Ion Radiation Therapy for Unresectable Sacral Chordoma: An Analysis of 188 Cases

Energy Technology Data Exchange (ETDEWEB)

Imai, Reiko, E-mail: r_imai@nirs.go.jp [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Kamada, Tadashi [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Araki, Nobuhito [Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Abe, Satoshi; Iwamoto, Yukihide; Ozaki, Toshifumi; Kanehira, Chihiro; Kaya, Mitsunori; Takahashi, Kazuhisa; Chuman, Hirokazu; Tsujii, Hirohiko; Tsuneyoshi, Masazumi; Nishida, Yoshihiro; Hiraga, Hiroaki; Hiruma, Toru; Machinami, Rikuo; Matsumine, Akihiko; Matsumoto, Seiichi; Morioka, Hideo; Yamaguchi, Takehiko; and others

2016-05-01

Purpose: To evaluate the results of carbon ion radiation therapy administered to 188 patients with unresectable primary sacral chordomas. Patients and Methods: One hundred eighty-eight patients were treated with carbon ion radiation therapy at a single institute between 1996 and 2013 and retrospectively analyzed. The median age was 66 years. The highest proximal invasion reached past S2 level in 137 patients. The median clinical target volume was 345 cm{sup 3}. One hundred six patients received 67.2 gray equivalents (GyE)/16 fractions (fr), 74 patients received 70.4 GyE/16 fr, 7 patients received 73.6 GyE/16 fr, and 1 patient received 64.0 GyE/16 fr. Results: The median follow-up period was 62 months (range, 6.8-147.5 months). Seventy percent of patients were followed for 5 years or until death. The 5-year local control, overall survival, and disease-free survival rates were 77.2%, 81.1%, and 50.3%, respectively. Forty-one patients had a local recurrence. Sex, tumor volume, level of proximal invasion, and irradiated dose were unrelated to local control. There was grade 3 toxicity of the peripheral nerves in 6 patients and grade 4 toxicity of the skin in 2 patients. Ambulation remained in 97% of patients. Conclusions: Carbon ion radiation therapy was safe and effective for unresectable chordoma and provided good local control and survival while preserving ambulation.

Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

Directory of Open Access Journals (Sweden)

Okita Yoshihiro

2010-02-01

Full Text Available Abstract Background The combination of gemcitabine (GEM and S-1, an oral 5-fluorouracil (5-FU derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. Methods Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed. Results The maximum concentration (Cmax, the area under the curve from the drug administration to the infinite time (AUCinf, and the elimination half-life (T1/2 of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax were not significantly different between S-1 administration with and without GEM. Conclusion There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.

A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck

Energy Technology Data Exchange (ETDEWEB)

Mesía, Ricard, E-mail: rmesia@iconcologia.net [Medical Oncology Department, Institut Català d' Oncologia L' Hospitalet, Barcelona (Spain); Vázquez, Silvia [Medical Oncology Department, Institut Català d' Oncologia L' Hospitalet, Barcelona (Spain); Grau, Juan J. [Medical Oncology Department, Hospital Clínic i Provincial, Barcelona (Spain); García-Sáenz, Jose A. [Medical Oncology Department, Hospital Clínico San Carlos, Madrid (Spain); Lozano, Alicia [Radiation Oncology Department, Institut Català d' Oncologia L' Hospitalet, Barcelona (Spain); García, Carlos [Medical Oncology Department, Hospital General Yagüe, Burgos (Spain); Carles, Joan [Medical Oncology Department, Hospital del Mar, Barcelona (Spain); Irigoyen, Antonio [Medical Oncology Department, Hospital Virgen de las Nieves, Granada (Spain); Mañós, Manel [Department of Otorhinolaryngology, Hospital de Bellvitge, Barcelona (Spain); García-Paredes, Beatriz [Medical Oncology Department, Hospital Clínico San Carlos, Madrid (Spain); Barco, Elvira del [Medical Oncology Department, Gregorio Marañón University Hospital, Madrid (Spain); Taberna, Miren [Medical Oncology Department, Institut Català d' Oncologia L' Hospitalet, Barcelona (Spain); Escobar, Yolanda [Medical Oncology Department, Gregorio Marañón University Hospital, Madrid (Spain); and others

2016-02-01

Purpose: Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. Methods and Materials: A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m{sup 2} day 1; cisplatin, 75 mg/m{sup 2} day 1; 5-fluorouracil [5-FU], 750 mg/m{sup 2} day 1-5) and cetuximab, 250 mg/m{sup 2} weekly (loading dose of 400 mg/m{sup 2}). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. Results: Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6

In vitro evidence for participation of DEC-205 expressed by thymic cortical epithelial cells in clearance of apoptotic thymocytes.

NARCIS (Netherlands)

Small, M; Kraal, G.

2003-01-01

Binding of apoptotic cells was compared after incubation of thymocytes with two clones of murine thymic stromal cells to which CD4(+)/CD8(+) thymocytes attach. With the BA/10, but not the BA/2, clone, thymocytes with apoptotic morphology were bound irreversibly. These tightly bound thymocytes were

Role of radiofrequency ablation in unresectable hepatocellular carcinoma: An Indian experience

International Nuclear Information System (INIS)

Kalra, Naveen; Kang, Mandeep; Bhatia, Anmol; Duseja, Ajay K; Dhiman, Radha K; Arya, Virendra K; Rajwanshi, Arvind; Chawla, Yogesh K; Khandelwal, Niranjan

2013-01-01

To evaluate the role of radiofrequency ablation (RFA) as an ablative technique in patients with unresectable hepatocellular carcinoma (HCC). A tertiary care center, prospective study. The subjects comprised 31 patients (30 males, one female; age range 32-75 years) with HCC (41 lesions) who were treated with image-guided RFA. The follow-up period ranged from 3 months to 6 years, and included a multiphasic computed tomography (CT) at 1, 3 and 6 months post-RFA, and every 6 months thereafter. Patient outcome was evaluated and the tumor recurrence, survival and complications were assessed. Discrete categorical data were presented as n (%) and continuous data as mean ± SD. Pearson correlation coefficient was used to determine the relationship between the different variables. Kaplan–Meier survival curve and Log-rank test were used to test the significance of difference between the survival time of the different groups. The ablation success rate was 80.5% (33/41 HCC lesions). 12.2% (5/41) of the lesions were managed with repeat RFA due to tumor residue. 4.9% (2/41) of the lesions were managed with repeated RFA and transarterial chemoembolization. Eight patients had tumor recurrence (five patients (16.1%) had local recurrence and three patients (9.6%) had distant recurrence). Eleven patients died within 3.5-20 months post-RFA. The survival rate at 1 year in patients who completed at least 1 year of follow-up was 63.3%. There was one major complication (1/31, 3.2%) in a patient with a subcapsular lesion and ascites. This patient developed hemoperitoneum in the immediate postprocedure period and was managed with endovascular treatment. She, however, had hepatic decompensation and died 48 h post-RFA. RFA is an effective and safe treatment for small unresectable HCC

Hepatic arterial 90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients.

Science.gov (United States)

Carr, Brian I

2004-02-01

Hepatocellular carcinoma (HCC) generally arises in a cirrhotic liver and, in most cases, is multifocal and bilobar. Although trans-hepatic artery chemoembolization (TACE) can be highly affective in shrinking tumors, it is limited by virtue of the damage that it can cause to the liver that is already damaged by chronic disease. A high priority in HCC research, after primary prevention and early detection, is to find new treatment modalities that are both effective and non-toxic to the underlying cirrhotic liver. A cohort of 65 patients with biopsy-proven unresectable HCC have been treated with hepatic arterial 90Yttrium microspheres (Therasphere), and the interim results are reported here. Only 1 cycle of Therasphere treatment ever was performed on 46 patients, 17 patients had 2 cycles, and 2 patients had 3 cycles of therapy. The median dose delivered was 134 Gy, typically as either 5 or 10 GBq (2-4 million microspheres). Clinical toxicities include 9 episodes of abdominal pain and 2 episodes of acute cholecystitis, requiring cholecystectomy. A main lab toxicity was elevated bilirubin which increased by more than 200% in 25 patients (30.5%) during 6 months of therapy, although 18 of these patients had only transient elevation. A prominent finding was prolonged and profound (>70%) lymphopenia in more than 75% of the patients, but without clinical significance. Forty-two patients (64.6%) had a substantial decrease in tumor vascularity in response to therapy, and 25 patients (38.4%) had a partial response, by computed tomography scan. Median survival for Okuda stage I patients (n=42) was 649 days (historical comparison 244) and for Okuda stage II patients (n=23) was 302 days (historical comparison 64 days). All patients were followed after therapy for a minimum of 6 months. There were 42 deaths, 21 due to liver failure, 6 from HCC progression, and 3 from metastases. Therasphere appears to be a relatively safe and effective therapy for advanced-stage unresectable HCC.

Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG)

International Nuclear Information System (INIS)

Huiskens, Joost; Gulik, Thomas M van; Lienden, Krijn P van; Engelbrecht, Marc RW; Meijer, Gerrit A; Grieken, Nicole CT van; Schriek, Jonne; Keijser, Astrid; Mol, Linda; Molenaar, I Quintus; Verhoef, Cornelis; Jong, Koert P de; Dejong, Kees HC; Kazemier, Geert; Ruers, Theo M; Wilt, Johanus HW de; Tinteren, Harm van; Punt, Cornelis JA

2015-01-01

Colorectal cancer patients with unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and the lack of consensus on criteria for (un)resectability complicates the interpretation of published results. CAIRO5 is a multicentre, randomised, phase 3 clinical study. Colorectal cancer patients with initially unresectable liver-only metastases are eligible, and will not be selected for potential resectability. The (un)resectability status is prospectively assessed by a central panel consisting of at least one radiologist and three liver surgeons, according to predefined criteria. Tumours of included patients will be tested for RAS mutation status. Patients with RAS wild type tumours will be treated with doublet chemotherapy (FOLFOX or FOLFIRI) and randomised between the addition of either bevacizumab or panitumumab, and patients with RAS mutant tumours will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or triple chemotherapy (FOLFOXIRI) plus bevacizumab. Radiological evaluation to assess conversion to resectability will be performed by the central panel, at an interval of two months. The primary study endpoint is median progression-free survival. Secondary endpoints are the R0/1 resection rate, median overall survival, response rate, toxicity, pathological response of resected lesions, postoperative morbidity, and correlation of baseline and follow-up evaluation with respect to outcomes by the central panel. CAIRO5 is a prospective multicentre trial that investigates the optimal systemic induction therapy for patients with initially unresectable, liver-only colorectal cancer metastases. CAIRO 5 is registered at European Clinical Trials Database (EudraCT) (2013-005435-24). CAIRO 5 is registered at ClinicalTrials.gov: NCT02162563, June 10, 2014

T-lymphocyte subsets, thymic size and breastfeeding in infancy

DEFF Research Database (Denmark)

Jeppesen, Dorthe Lisbeth; Hasselbalch, Helle; Lisse, Ida M

2004-01-01

We followed the changes in concentration of T-lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4......+ and CD8+ cells. Two different populations of infants between birth and 1 year of age were examined. Study Group I: infants with a variable duration of breastfeeding. Study Group II: long-term breastfed infants. In both groups a correlation was found between CD8+ cells and the thymic index at 10 months...... to 10 months of age; and a positive correlation between the number of breastfeedings per day at 8 months of age, and an increase in CD4+ cells from 8 to 10 months of age (p Breastfeeding might have both a current and long...

Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts

DEFF Research Database (Denmark)

Nielsen, S. D.; Jeppesen, D. L.; Kolte, L.

2001-01-01

and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts (459.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/microL, P mothers were found (frequency of CD4(+) cells with TRECs was 3.6% +/- 0.7% compared with 14.3% +/- 2.2% in controls, P ...). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T...... cells in FTOCs. In conclusion, lower numbers of naive CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-positive mothers may be due to impaired progenitor cell function....

T-cell receptor excision circles (TREC) in CD4+ and CD8+ T-cell subpopulations in atopic dermatitis and psoriasis show major differences in the emission of recent thymic emigrants

DEFF Research Database (Denmark)

Just, Helle L; Deleuran, Mette; Vestergaard, Christian

2008-01-01

. In contrast, both men and women with psoriasis had significantly reduced TREC levels, which were, on average, only 30% of that of healthy persons. In atopic dermatitis the levels of TREC declined with increasing levels of IgE, disease intensity and extent of eczema. Furthermore, patients with atopic......-cells, this indicates that atopic dermatitis patients can have compensatory emissions of thymic emigrants, whereas psoriatic patients do not, thus supporting different thymic function in these two diseases....

Factors Predicting Survival after Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Farina M. Hanif

2014-10-01

Full Text Available Background: Transarterial chemoembolization is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma. Survival after transarterial chemoembolization can be highly variable. The purpose of this study is to identify the factors that predict overall survival of patients with unresectable hepatocellular carcinoma who undergo transarterial chemoembolization as the initial therapy. Methods:We included patients who underwent transarterial chemoembolization from 2007 to 2012 in this study. Patient’s age, gender, cause of cirrhosis, Child-Turcotte-Pugh score, model of end-stage liver disease score, Cancer of the Liver Italian Program score, Okuda stage, alpha- fetoprotein level, site, size and number of tumors were recorded. Radiological response to transarterial chemoembolization was assessed by computerized tomography scan at 1 and 3 months after the procedure. Repeat sessions of transarterial chemoembolization were performed according to the response. We performed survival assessment and all patients were assessed for survival at the last follow-up. Results: Included in this study were 71 patients of whom there were 57 (80.3 % males, with a mean age of 51.9±12.1 years (range: 18-76 years. The mean follow-up period was 12.5±10.7 months. A total of 31 (43.7% patients had only one session of transarterial chemoembolization, 17 (23.9% underwent 2 and 11 (15.5% had 3 or more sessions. On univariate analysis, significant factors that predicted survival included serum bilirubin (P=0.02, esophageal varices (P=0.002, Cancer of the Liver Italian Program score (P=0.003, tumor size (P=0.005, >3 sessions of transarterial chemoembolization (P=0.006 and patient's age (P=0.001. Cox regression analysis showed that tumor size of 1 transarterial chemoembolization session (P=0.004 were associated with better survival. Conclusion: Our study demonstrates that survival after transarterial chemoem- bolization is predicted by tumor size

Combined Treatment of Residual, Recurrent and Unresectable Gastric Cancer

International Nuclear Information System (INIS)

Bae, Hoon Sik

1990-01-01

A series of 25 patients with residual, recurrent, and unresectable gastric cancer received various combination of surgery, radiotherapy (RT), chemotherapy (CT), and hyperthermia (HT). They were placed INTO 7 categories; 1) CT and HT-14 patients; 2) RT and HT-15 patients; 3) surgery, RT and HT-2 patients; 4) surgery, RT, HT and CT-1 patient; 5) RT, HT and CT-1 patient; 6) RT and CT-1 patient; 7) RT alone-1 patient. Three patients had curative resection. 21 patients received irradiation with tightly contoured portals to spare as much small bowel, kidney and marrow as possible. Hyperthermia was applied regionally once or twice a week for 23 patients using 8 MHz radiofrequency capacitive heating device (Thermotron RF-8). HT was given approximately 30 min after RT. 7 patients were treated with CT: 4 patients received HT and concomitant Mitomycin-C; 3 patients received HT and sequential 5-FU+Adriamycin+Mitomycin-C. There was not any treatment related deaths. There was also no evidence of treatment related problems with liver, kidney, stomach, or spinal cord except only one case of transient diabetic ketoacidosis. The tumor response was evaluable in 22 patients. None achieved complete remission. 11(50%) achieved partial remission. The response rate was correlated with total radiation dose and achieved maximum temperature. 9 of 14 (64%) received more than 4000 cGy showed partial remission; especially, all 3 patients received more than 5500 cGy achieved partial response. 8 of the 12 patients (67%) who achieved maximal temperature more than 41 .deg. C showed partial response in comparing with 25% (2 of 8 patients, below 41 .deg. C). The numbers of HT, however, was not correlated with the response. 3 of the 25 patients (12%) remain alive. The one who was surgically unresectable and underwent irradiation alone is in progression of the disease with distant metastases. The remaining two patients with curative resection are alive with free of disease, 24 and 35 months

Effect of Boron on Thymic Cytokine Expression, Hormone Secretion, Antioxidant Functions, Cell Proliferation, and Apoptosis Potential via the Extracellular Signal-Regulated Kinases 1 and 2 Signaling Pathway.

Science.gov (United States)

Jin, Erhui; Ren, Man; Liu, Wenwen; Liang, Shuang; Hu, Qianqian; Gu, Youfang; Li, Shenghe

2017-12-27

Boron is an essential trace element in animals. Appropriate boron supplementation can promote thymus development; however, a high dose of boron can lead to adverse effects and cause toxicity. The influencing mechanism of boron on the animal body remains unclear. In this study, we examined the effect of boron on cytokine expression, thymosin and thymopoietin secretion, antioxidant function, cell proliferation and apoptosis, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in the thymus of rats. We found that supplementation with 10 and 20 mg/L boron to the drinking water significantly elevated levels of interleukin 2 (IL-2), interferon γ (IFN-γ), interleukin 4 (IL-4), and thymosin α1 in the thymus of rats (p boron had no apparent effect on many of the above indicators. In contrast, supplementation with 480 and 640 mg/L boron had the opposite effect on the above indicators in rats and elevated levels of pro-inflammatory cytokines, such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α) (p boron to the drinking water had a U-shaped dose-effect relationship with thymic cytokine expression, hormone secretion, antioxidant function, cell proliferation, and apoptosis. Specifically, supplementation with 10 and 20 mg/L boron promoted thymocyte proliferation and enhanced thymic functions. However, supplementation with 480 and 640 mg/L boron inhibited thymic functions and increased the number of apoptotic thymocytes, suggesting that the effects of boron on thymic functions may be caused via the ERK1/2 signaling pathway.

Paclitaxel, cisplatin, 5-fluorouracil and radiotherapy in the management of advanced squamous cell carcinoma of the head and neck. A phase II trial

International Nuclear Information System (INIS)

Merlano, Marco; Russi, Elvio G.; Numico, Gianmauro; Colantonio, Ida; Garrone, Ornella; Pelissero, Antonio; Granetto, Cristina; Gasco, Milena; Di Costanzo, Gianna; Heouaine, Abdelhamid; Vigna Taglianti, Riccardo; Cipolat, Marco

2005-01-01

Aim of the present study was to test, activity and toxicity of a rapidly alternating chemoradiation (paclitaxel based) in 31 patients with unresectable, locally advanced or recurrent after surgery, head and neck cancer. Three-year overall survival and progression-free survival were 61.4 and 73.7%, respectively. Main side effects remain a major problem

Thymic Nurse Cells Participate in Heterotypic Internalization and Repertoire Selection of Immature Thymocytes; Their Removal from the Thymus of Autoimmune Animals May be Important to Disease Etiology.

Science.gov (United States)

Guyden, J C; Martinez, M; Chilukuri, R V E; Reid, V; Kelly, F; Samms, M-O D

2015-01-01

Thymic nurse cells (TNCs) are specialized epithelial cells that reside in the thymic cortex. The initial report of their discovery in 1980 showed TNCs to contain up to 200 thymocytes within specialized vacuoles in their cytoplasm. Much has been reported since that time to determine the function of this heterotypic internalization event that exists between TNCs and developing thymocytes. In this review, we discuss the literature reported that describes the internalization event and the role TNCs play during T cell development in the thymus as well as why these multicellular complexes may be important in inhibiting the development of autoimmune diseases.

Tumor carcinóide do timo - Caso clínico Thymic carcinoid - case report

Directory of Open Access Journals (Sweden)

Lina Carvalho

2010-01-01

have an excellent prognosis, while locally invasive tumours in more advanced stages have a relatively poor prognosis as happens with thymomas. Complete surgical removal is the critical factor for long-term survival rates and the basis for treatment of all thymic tumours, independent of histologic type. As an important cause of death, especially in carcinoid tumours associated with MEN-1 and Cushing’s syndrome, some authors advocate the need for profilactic thymectomy in these patients.

Living Donor Liver Transplantation for Unresectable Liver Adenomatosis Associated with Congenital Absence of Portal Vein: A Case Report and Literature Review.

Science.gov (United States)

Brasoveanu, Vladislav; Ionescu, Mihnea Ioan; Grigorie, Razvan; Mihaila, Mariana; Bacalbasa, Nicolae; Dumitru, Radu; Herlea, Vlad; Iorgescu, Andreea; Tomescu, Dana; Popescu, Irinel

2015-09-19

Abernethy malformation (AM), or congenital absence of portal vein (CAPV), is a very rare disease which tends to be associated with the development of benign or malignant tumors, usually in children or young adults. We report the case of a 21-year-old woman diagnosed with type Ib AM (portal vein draining directly into the inferior vena cava) and unresectable liver adenomatosis. The patient presented mild liver dysfunction and was largely asymptomatic. Living donor liver transplantation was performed using a left hemiliver graft from her mother. Postoperatively, the patient attained optimal liver function and at 9-month follow-up has returned to normal life. We consider that living donor liver transplantation is the best therapeutic solution for AM associated with unresectable liver adenomatosis, especially because compared to receiving a whole liver graft, the waiting time on the liver transplantation list is much shorter.

Beam angle selection for intensity-modulated radiotherapy (IMRT) treatment of unresectable pancreatic cancer: are noncoplanar beam angles necessary?

Science.gov (United States)

Chang, D S; Bartlett, G K; Das, I J; Cardenes, H R

2013-09-01

External beam radiation therapy with concurrent chemotherapy (CRT) is widely used for the treatment of unresectable pancreatic cancer. Noncoplanar (NCP) 3D conformal radiotherapy (3DCRT) and coplanar (CP) IMRT have been reported to lower the radiation dose to organs at risk (OARs). The purpose of this article is to examine the utility of noncoplanar beam angles in IMRT for the management of pancreatic cancer. Sixteen patients who were treated with CRT for unresectable adenocarcinoma of the pancreatic head or neck were re-planned using CP and NCP beams in 3DCRT and IMRT with the Varian Eclipse treatment planning system. Compared to CP IMRT, NCP IMRT had similar target coverage with slightly increased maximum point dose, 5,799 versus 5,775 cGy (p = 0.008). NCP IMRT resulted in lower mean kidney dose, 787 versus 1,210 cGy (p kidney dose, but did not improve other dose-volume criteria. The use of NCP beam angles is preferred only in patients with risk factors for treatment-related kidney dysfunction.

Early outcomes of radiofrequency ablation in unresectable metastatic colorectal cancer from a tertiary cancer hospital in India

Directory of Open Access Journals (Sweden)

Suyash Kulkarni

2017-01-01

Full Text Available Aims: The study was carried out to evaluate the early outcomes using Radiofrequency Ablation (RFA for unresectable liver metastases in the management of metastatic colorectal cancer (mCRC from an area of low endemicity. Material and Methods: 60 Patients with unresectable colorectal liver metastases had undergone 88 sessions of RFA from January 2007 till December 2013. The results were retrospectively analysed to evaluate the outcomes in terms of efficacy and survival rates. Results: The median follow up of patients in our series was 24.8months. 35/52 (67.3% patients had complete response at 3 months while 8 patients were lost to follow up. Of the 17 patients who had recurrence, 4 (23.5% were at the ablated site while 13 patients (76.4% progressed elsewhere. Abdominal pain was commonest post procedural symptom (20%. There was no procedure related mortality or any major complications. Mean disease free interval and Progression free survival was 6.7 and 13.1 months. Estimated median survival in patients with liver limited disease and those with small lesion (3 cm was associated with decreased survival.

Thymic and lymph node mesenchymal subsets can be derived from PDGFRα/β+Gp38+CD34+ICAM1- vascular adventitial precursors

DEFF Research Database (Denmark)

Sitnik, Katarzyna Maria; Wendland, Kerstin; Weishaupt, Holger

While discrete Gp38- and Gp38+ mesenchymal populations have previously been described in the lymph nodes (LNs) and in the thymus the putative relationship between LN and thymic mesenchymal cells remains unclear. Here, using transcriptome profiling as well as phenotypic and localization studies we...

Results of combined modality treatment in patients with primary unresectable cancer of the oral cavity

International Nuclear Information System (INIS)

Kawecki, A.; Starosciak, S.; Towpik, E.; Jagielska, B.; Lenartowicz, B.; Pietras, M.; Szutkowski, Z.; Kiprian, D.

2001-01-01

Neoadjuvant chemotherapy may improve the results of treatment for primarily unresectable cancer of the oral cavity. The aim of this study was to estimate the tolerance and early results of neoadjuvant chemotherapy followed by surgical resection of oral cavity cancer, with immediate reconstruction and adjuvant radiotherapy. 56 patients hospitalized at the Department of Head and Neck Cancer of the Maria Sklodowska-Curie Memorial Cancer Centre - Institute of Oncology between August 1997 and June 2000 were enrolled for the purpose of the study. When tumour regresion was observed after 2-4 courses of neoadjuvant chemotherapy consisting of cisplatin, 5-fluorouracil, methotrexate, vinblastin, etoposide and leucovorin, the patients were referred for surgical resection with immediate reconstruction, followed by adjuvant radiotherapy. Regression of the primary tumor and lymph nodes of the neck was observed in 41 patients, all of whom were referred for radical surgery followed by adjuvant radiotherapy. The tolerance of combined treatment was acceptable. Complete regression was obtained in 37/56 patients. During observation 12 patients failed due to locoregional progression and 2 due to distant metastases. 23/56 patients (41 %) are alive without evidence of disease. Neoadjuvant chemotherapy allows for radical resection in a majority of patients with primarily unresectable cancer of the oral cavity. The tolerance of treatment is good. What is important, radiotherapy and chemotherapy do not impair wound healing and vascularity of musculo-cutaneous island flaps

Efficacy of Endoscopic Over 3-branched Partial Stent-in-Stent Drainage Using Self-expandable Metallic Stents in Patients With Unresectable Hilar Biliary Carcinoma.

Science.gov (United States)

Uchida, Daisuke; Kato, Hironari; Muro, Shinichiro; Noma, Yasuhiro; Yamamoto, Naoki; Horiguchi, Shigeru; Harada, Ryo; Tsutsumi, Koichiro; Kawamoto, Hirofumi; Okada, Hiroyuki; Yamamoto, Kazuhide

2015-07-01

The treatment of biliary stricture is crucially important for continuing stable chemotherapy for unresectable biliary carcinoma; however, there is no consensus regarding the use of hilar biliary drainage. In this study, we examined the efficacy of endoscopic over 3-branched biliary drainage using self-expandable metallic stents (SEMSs) in patients with unresectable malignant hilar biliary stricture (HBS). A total of 77 patients with unresectable HBS treated with a SEMS and chemotherapy were retrospectively reviewed. There were 59 patients with cholangiocarcinoma and 18 patients with gallbladder carcinoma. The patients were divided into 2 groups (4- or 3-branched group and 2- or 1-branched group) and compared with respect to the duration of stent patency and overall survival. A comparison of the patients' baseline characteristics showed no significant differences between the 4- or 3-branched group and the 2- or 1-branched group. Neither the duration of patency nor survival time exhibited significant differences between the 2 groups, although, among the patients achieving disease control , the duration of patency period and survival time of the 4- or 3-branched group were significantly higher than those observed in the 2- or 1-branched group (P=0.0231 and 0.0466). The use of endoscopic over 3-branched biliary drainage with a SEMS may improve the duration of patency in patients with HBS.

Primary colectomy in patients with stage IV colon cancer and unresectable distant metastases improves overall survival: results of a multicentric study.

Science.gov (United States)

Karoui, Mehdi; Roudot-Thoraval, Françoise; Mesli, Farida; Mitry, Emmanuel; Aparicio, Thomas; Des Guetz, Gaetan; DesGuetz, Gaetan; Louvet, Christophe; Landi, Bruno; Tiret, Emmanuel; Sobhani, Iradj

2011-08-01

Whether patients with stage IV colon cancer and unresectable distant metastases should be managed by primary colectomy followed by chemotherapy or immediate chemotherapy without resection of the primary tumor is still controversial. This study aimed to evaluate predictive factors associated with survival in patients with stage IV colon cancer and unresectable distant metastases. This large retrospective multicentric study included 6 academic hospitals. This study was conducted at 6 Paris University Hospitals (Assistance Publique-Hôpitaux de Paris; Saint Antoine, Henri Mondor, Ambroise Paré, Hôpital Europeen Gorges Pompidou, Bichat, and Avicenne). Between 1998 and 2007, 208 patients with good performance status and stage IV colon cancer with unresectable distant metastases received chemotherapy, either as initial management or after primary tumor resection. Survival was estimated by use of the Kaplan-Meier method. Factors associated with survival were tested by means of a log-rank test. Results were expressed as median values with 95% confidence intervals. Factors independently related to survival were tested using a Cox regression model adjusted for a propensity score. Of the 208 patients, 85 underwent colectomy before chemotherapy, whereas 123 were treated with use of primary chemotherapy with or without biotherapy. At univariate analysis, the following factors were significantly associated with survival: primary colectomy (P = .031), secondary curative surgery (P < .001), well-differentiated primary tumor (P < .001), exclusive liver metastases (P < .027), absence of need for colonic stent (P = .009), and addition of antiangiogenic (P = .001) or anti-epidermal growth factor receptor (P = .013) drugs to chemotherapy. After Cox multivariate analysis and after adjusting for the propensity score, all of these factors, with the exception of two, colonic stent and anti-epidermal growth factor receptor drug, were found to be independently associated with overall

Y-90 microshperes in the treatment of unresectable hepatocellular carcinoma.

Science.gov (United States)

Al-Kalbani, Abdullah; Kamel, Yasser

2008-04-01

A small percentage of patients with hepatocellular carcinoma (HCC) are candidates for curative treatment in form of resection or transplantation. There are different treatment options for unresectable HCC-like local ablative therapies and recently systemic therapy with Sorafenib. All of these have variable response rate and had been proven to improve survival. In the last few years, there is a growing interest in TheraSphere radioembolization. It consists of yttrium90 (Y-90) embedded into nonbiodegradable glass microspheres. It is selectively administered by intraarterial hepatic injection giving high doses of radiation to the tumor and sparing the liver parenchyma. It has been shown to improve survival and used as a bridge to transplantation and to downstage tumors for resection. Therasphere seems to have favorable safety profile and has been used in patients with portal vein thrombosis with successful outcome.

Generation of Functional Thymic Epithelium from Human Embryonic Stem Cells that Supports Host T Cell Development

OpenAIRE

Parent, Audrey V.; Russ, Holger A.; Khan, Imran S.; LaFlam, Taylor N.; Metzger, Todd C.; Anderson, Mark S.; Hebrok, Matthias

2013-01-01

Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into th...

Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro

Directory of Open Access Journals (Sweden)

Marvin Paulo Lins

Full Text Available BACKGROUND: Several evidences indicate that hormones and neuropeptides function as immunomodulators. Among these, growth hormone (GH is known to act on the thymic microenvironment, supporting its role in thymocyte differentiation. The aim of this study was to evaluate the effect of GH on human thymocytes and thymic epithelial cells (TEC in the presence of laminin. RESULTS: GH increased thymocyte adhesion on BSA-coated and further on laminin-coated surfaces. The number of migrating cells in laminin-coated membrane was higher in GH-treated thymocyte group. In both results, VLA-6 expression on thymocytes was constant. Also, treatment with GH enhanced laminin production by TEC after 24 h in culture. However, VLA-6 integrin expression on TEC remained unchanged. Finally, TEC/thymocyte co-culture model demonstrated that GH elevated absolute number of double-negative (CD4-CD8- and single-positive CD4+ and CD8+ thymocytes. A decrease in cell number was noted in double-positive (CD4+CD8+ thymocytes. CONCLUSIONS: The results of this study demonstrate that GH is capable of enhancing the migratory capacity of human thymocytes in the presence of laminin and promotes modulation of thymocyte subsets after co-culture with TEC.

Treatment of primary unresectable carcinoma of the pancreas with I-125 implantation

Energy Technology Data Exchange (ETDEWEB)

Peretz, T.; Nori, D.; Hilaris, B.; Manolatos, S.; Linares, L.; Harrison, L.; Anderson, L.L.; Fuks, Z.; Brennan, M.F. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA))

1989-11-01

Between January 1 1974 and October 31 1987, 98 patients with biopsy proven unresectable adenocarcinoma of the pancreas were treated with I-125 implants during laparotomy. Presenting symptoms were pain, jaundice, and weight loss. All patients underwent laparotomy and surgical staging. Thirty patients had T1NoMo disease, 47 patients had T2-3NoMo disease, and 21 patients had significant regional lymph node involvement (T1-3N1Mo). The surgical procedure performed was biopsy only (16 patients), gastric bypass, biliary bypass, and partial or total pancreatectomy with incomplete resection. The total activity and the number of seeds used were determined from the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Stereoshift localization X ray films were taken 3-6 days after operation. The mean activity, minimal peripheral dose (MPD), and volume of the implants were 35 mCi, 13,660 cGy, and 53 cm3, respectively. In addition, 27 patients received postoperative external irradiation and 27 patients received chemotherapy. Postoperative complications were observed in 19 patients. These included post-operative death (1 patient), biliary fistula (4), intraabdominal abscess (4), GI bleeding (3), gastric or small bowel obstruction (6), sepsis (5), and deep vein thrombophlebitis (4). Pain relief was obtained in 37/57 patients (65%) presenting with pain. A multivariate analysis showed that four factors significantly affected survival: T stage, N stage, administration of chemotherapy, and more than 30% reduction in the size of the implant on follow-up films. The median survival for the entire group was 7 months. A subgroup of patients with T1No stage disease who received chemotherapy survived 18.5 months. The indications for I-125 seed implantation in unresectable carcinoma of the pancreas are discussed.

Treatment of primary unresectable carcinoma of the pancreas with I-125 implantation

International Nuclear Information System (INIS)

Peretz, T.; Nori, D.; Hilaris, B.; Manolatos, S.; Linares, L.; Harrison, L.; Anderson, L.L.; Fuks, Z.; Brennan, M.F.

1989-01-01

Between January 1 1974 and October 31 1987, 98 patients with biopsy proven unresectable adenocarcinoma of the pancreas were treated with I-125 implants during laparotomy. Presenting symptoms were pain, jaundice, and weight loss. All patients underwent laparotomy and surgical staging. Thirty patients had T1NoMo disease, 47 patients had T2-3NoMo disease, and 21 patients had significant regional lymph node involvement (T1-3N1Mo). The surgical procedure performed was biopsy only (16 patients), gastric bypass, biliary bypass, and partial or total pancreatectomy with incomplete resection. The total activity and the number of seeds used were determined from the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Stereoshift localization X ray films were taken 3-6 days after operation. The mean activity, minimal peripheral dose (MPD), and volume of the implants were 35 mCi, 13,660 cGy, and 53 cm3, respectively. In addition, 27 patients received postoperative external irradiation and 27 patients received chemotherapy. Postoperative complications were observed in 19 patients. These included post-operative death (1 patient), biliary fistula (4), intraabdominal abscess (4), GI bleeding (3), gastric or small bowel obstruction (6), sepsis (5), and deep vein thrombophlebitis (4). Pain relief was obtained in 37/57 patients (65%) presenting with pain. A multivariate analysis showed that four factors significantly affected survival: T stage, N stage, administration of chemotherapy, and more than 30% reduction in the size of the implant on follow-up films. The median survival for the entire group was 7 months. A subgroup of patients with T1No stage disease who received chemotherapy survived 18.5 months. The indications for I-125 seed implantation in unresectable carcinoma of the pancreas are discussed

Human epidermal growth factor receptor2 expression in unresectable gastric cancers: Relationship with CT characteristics

Energy Technology Data Exchange (ETDEWEB)

Lee, Jeong Sub [Dept. of Radiology, Jeju National University Hospital, Jeju (Korea, Republic of); Kim, Se Hyung; Im, Seock Ah; Kim, Min A; Han, Joon Koo [Seoul National University Hospital, Seoul (Korea, Republic of)

2017-09-15

To retrospectively analyze the qualitative CT features that correlate with human epidermal growth factor receptor 2 (HER2)-expression in pathologically-proven gastric cancers. A total of 181 patients with pathologically-proven unresectable gastric cancers with HER2-expression (HER2-positive [n = 32] and negative [n = 149]) were included. CT features of primary gastric and metastatic tumors were reviewed. The prevalence of each CT finding was compared in both groups. Thereafter, binary logistic regression determined the most significant differential CT features. Clinical outcomes were compared using Kaplan-Meier method. HER2-postive cancers showed lower clinical T stage (21.9% vs. 8.1%; p = 0.015), hyperattenuation on portal phase (62.5% vs. 30.9%; p = 0.003), and was more frequently metastasized to the liver (62.5% vs. 32.2%; p = 0.001), than HER2-negative cancers. On binary regression analysis, hyperattenuation of the tumor (odds ratio [OR], 4.68; p < 0.001) and hepatic metastasis (OR, 4.43; p = 0.001) were significant independent factors that predict HER2-positive cancers. Median survival of HER2-positive cancers (13.7 months) was significantly longer than HER2-negative cancers (9.6 months) (p = 0.035). HER2-positive gastric cancers show less-advanced T stage, hyperattenuation on the portal phase, and frequently metastasize to the liver, as compared to HER2-negative cancers.

Human epidermal growth factor receptor2 expression in unresectable gastric cancers: Relationship with CT characteristics

International Nuclear Information System (INIS)

Lee, Jeong Sub; Kim, Se Hyung; Im, Seock Ah; Kim, Min A; Han, Joon Koo

2017-01-01

To retrospectively analyze the qualitative CT features that correlate with human epidermal growth factor receptor 2 (HER2)-expression in pathologically-proven gastric cancers. A total of 181 patients with pathologically-proven unresectable gastric cancers with HER2-expression (HER2-positive [n = 32] and negative [n = 149]) were included. CT features of primary gastric and metastatic tumors were reviewed. The prevalence of each CT finding was compared in both groups. Thereafter, binary logistic regression determined the most significant differential CT features. Clinical outcomes were compared using Kaplan-Meier method. HER2-postive cancers showed lower clinical T stage (21.9% vs. 8.1%; p = 0.015), hyperattenuation on portal phase (62.5% vs. 30.9%; p = 0.003), and was more frequently metastasized to the liver (62.5% vs. 32.2%; p = 0.001), than HER2-negative cancers. On binary regression analysis, hyperattenuation of the tumor (odds ratio [OR], 4.68; p < 0.001) and hepatic metastasis (OR, 4.43; p = 0.001) were significant independent factors that predict HER2-positive cancers. Median survival of HER2-positive cancers (13.7 months) was significantly longer than HER2-negative cancers (9.6 months) (p = 0.035). HER2-positive gastric cancers show less-advanced T stage, hyperattenuation on the portal phase, and frequently metastasize to the liver, as compared to HER2-negative cancers

Combined Therapies for the Treatment of Technically Unresectable Liver Malignancies: Bland Embolization and Radiofrequency Thermal Ablation within the Same Session

International Nuclear Information System (INIS)

Bonomo, Guido; Della Vigna, Paolo; Monfardini, Lorenzo; Orgera, Gianluigi; Chiappa, Antonio; Bianchi, Paolo Pietro; Zampino, Maria Giulia; Orsi, Franco

2012-01-01

Purpose: This retrospective study evaluated the feasibility, efficacy, and safety of combining transcatheter arterial embolization (TAE) with radiofrequency thermal ablation (RFA) in a single session for the treatment of technically unresectable liver-only malignancies. Methods: From May 2006 to January 2011, a total of 30 patients affected by liver metastases with single or multiple unresectable liver-only lesions underwent a combined treatment with TAE followed by RFA in the same session, for a total of 36 treated lesions. Patients were extrapolated from a cohort of patients discussed within the weekly institutional tumor board. TAE was performed by using 100 μm microspheres; RFA was performed immediately after TAE by positioning the electrode needle via ultrasound and/or computed tomographic guidance. Local tumor responses and procedure-related complications were evaluated. Results: Completion of both procedures was obtained in all patients for all 36 lesions. Liver lesions had a maximum axial diameter ranging 16–59 mm. Postintervention unenhanced ablated areas ranged 28–104 mm in maximum axial diameter. Safety margins ranged 1–30.5 mm. Complete response, defined as complete devascularization at computed tomography, was obtained in all treated lesions for a maximum period of 12 months. Tumor relapse was observed in one patient at 12 months. Sixteen patients developed new liver lesions or progressive systemic disease during follow-up. Nine patients were still disease-free. Seven patients died as a result of systemic progressive disease. One major treatment-related complication was observed. Conclusions: In patients with technically unresectable liver-only malignancies, single-session combined TAE-RFA is an effective and safe treatment.

Clinical experience of intrapleural administration of fibrin glue for secondary pneumothorax with advanced lung cancer

International Nuclear Information System (INIS)

Nishino, Takeshi; Takizawa, Hiromitsu; Yoshida, Mitsuteru; Kawakami, Yukikiyo; Sakiyama, Shoji; Kondo, Kazuya

2014-01-01

Secondary pneumothorax with advanced lung cancer is an intractable and serious pathosis, which directly aggravates patients' Quality of Life (QOL) and prognosis. We first select the intrapleural administration of fibrin glue for secondary pneumothorax with advanced lung cancer. From April 2009 to May 2012, we encountered 5 patients who developed secondary pneumothorax during treatment for advanced lung cancer. Their average age was 60.8 years old, and 4 of them had squamous cell carcinoma, 1 had adenocarcinoma, and all had unresectable advanced lung cancer. In 4 of them, the point of air leakage could be detected by pleurography, and leakage could be stopped by the intrapleural administration of fibrin glue. All of them could receive chemotherapy or radiotherapy after treatment for secondary pneumothorax. The intrapleural administration of fibrin glue may be an effective and valid treatment for intractable secondary pneumothorax with advanced lung cancer. (author)

A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma.

Science.gov (United States)

Sakane, Tadashi; Murase, Takayuki; Okuda, Katsuhiro; Takino, Hisashi; Masaki, Ayako; Oda, Risa; Watanabe, Takuya; Kawano, Osamu; Haneda, Hiroshi; Moriyama, Satoru; Saito, Yushi; Yamada, Takeshi; Nakanishi, Ryoichi; Inagaki, Hiroshi

2018-01-23

Currently, four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays. The cases of 53 patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays showed similar scores in each case. Histopathologically, high TC scores were observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no significant relationships among the IC scores in the four assays. In SqCCs, the high expression of PD-L1 (defined as ≥50% TC score) in TCs tended to be associated with early stage cancer. The patients with high expression levels of PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In thymic carcinomas, the staining pattern showed high concordance among the four assays when TCs - rather than ICs - were stained. High PD-L1 positivity in TCs, especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a promising therapeutic approach.

Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

Directory of Open Access Journals (Sweden)

Samantha J Westrop

Full Text Available HIV-1(+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+ individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

Directory of Open Access Journals (Sweden)

Mélanie Saint-Jean

2018-01-01

Full Text Available Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs. This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2 regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4 or IV (n=6 melanoma. All but 1 patient with unresectable stage III melanoma (1st line had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation.

Analysis of the expression level and methylation of tumor protein p53, phosphatase and tensin homolog and mutS homolog 2 in N-methyl-N-nitrosourea-induced thymic lymphoma in C57BL/6 mice.

Science.gov (United States)

Huo, Xueyun; Li, Zhenkun; Zhang, Shuangyue; Li, Changlong; Guo, Meng; Lu, Jing; Lv, Jianyi; Du, Xiaoyan; Chen, Zhenwen

2017-10-01

Tumorigenesis is often caused by somatic mutation or epigenetic changes in genes that regulate aspects of cell death, proliferation and survival. Although the functions of multiple tumor suppressor genes have been well studied in isolation, how these genes cooperate during the progression of a single tumor remains unclear in numerous cases. The present study used N-methyl-N-nitrosourea (MNU), one of the most potent mutagenic nitrosourea compounds, to induce thymic lymphoma in C57BL/6J mice. Subsequently, the protein expression levels of phosphatase and tensin homolog (PTEN), transformation protein 53 and mutS homolog 2 (MSH2) were evaluated concomitantly in the thymus, liver, kidney and spleen of MNU-treated mice by western blotting. To determine whether changes in expression level were due to aberrant epigenetic regulation, the present study further examined the methylation status of each gene by MassARRAY analysis. During the tumorigenesis process of an MNU-induced single thymic lymphoma, the expression level of PTEN was revealed to be reduced in thymic lymphoma samples but not in normal or non-tumor thymus tissue samples. Furthermore, a marked reduction of P53 expression levels were demonstrated in thymic lymphomas and spleens with a metastatic tumor. Conversely, MSH2 upregulation was identified only in liver, kidney, and spleen samples that were infiltrated by thymic lymphoma cells. Furthermore, the present study revealed that a number of 5'-C-phosphate-G-3' sites located in the promoter of aberrantly expressed genes had significantly altered methylation statuses. These results improve the understanding of the course of mutagen-induced cancer, and highlight that epigenetic regulation may serve an important function in cancer.

Phase I Results of Vinorelbine With Concurrent Radiotherapy in Elderly Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer: West Japan Thoracic Oncology Group (WJTOG3005-DI)

Energy Technology Data Exchange (ETDEWEB)

Harada, Hideyuki, E-mail: h.harada@scchr.jp [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Seto, Takashi [Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka (Japan); Igawa, Satoshi [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Tsuya, Asuka [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Wada, Mayuko [Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Kaira, Kyoichi; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Hayakawa, Kazushige [Department of Radiology, Kitasato University School of Medicine, Kanagawa (Japan); Nishimura, Tetsuo [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Masuda, Noriyuki [Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan)

2012-04-01

Purpose: To investigate the safety and efficacy of concurrent vinorelbine and thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 71 years of age or older with unresectable Stage III NSCLC. Patients were treated with thoracic radiotherapy (60 Gy) and concurrent vinorelbine (20 mg/m{sup 2} in Level 1 and 25 mg/m{sup 2} in Level 2) on Days 1 and 8 every 3 weeks for two cycles, followed by adjuvant vinorelbine (25 mg/m{sup 2}) on Days 1 and 8 every 3 weeks for two cycles. Results: Four patients were enrolled at Level 1. One patient experienced Grade 3 febrile neutropenia at Level 1 and the dose was escalated to Level 2. At Level 2, 2 of 6 patients experienced dose-limiting toxicities (Grade 4 neutropenia in 1 patient and Grade 3 infection in another). Three of 6 patients developed late Grade 2 or 3 pneumonitis. Therefore, the dose was de-escalated to Level 1. An additional 6 patients were enrolled at Level 1, 4 of whom experienced dose-limiting toxicities (incomplete radiotherapy because of Grade 2 pneumonitis in 1 patient and Grade 3 infection in 1, Grade 3 febrile neutropenia in 1, and Grade 3 esophagitis in 1). Moreover, late Grade 3 pneumothorax and Grade 5 pneumonitis occurred in 1 and 1 patient, respectively. Overall, Grade 2, 3 and 5 pneumonitis occurred in 3, 3, and 1 among 16 patients, respectively. Conclusions: Concurrent vinorelbine and thoracic radiotherapy resulted in a high incidence of severe pneumonitis when the standard dose of this agent was used for elderly patients. We therefore recommend caution in the use of this regimen and schedule for elderly patients.

Nur77 nuclear import and its NBRE-binding activity in thymic lymphoma cells are regulated by different mechanisms sensitive to FK506 or HA1004

International Nuclear Information System (INIS)

Kochel, Izabela; Rapak, Andrzej; Ziolo, Ewa; Strzadala, Leon

2005-01-01

Thymic lymphoma cells restore their sensitivity to ionomycin-induced apoptosis when treated with FK506 or HA1004. In apoptosis-resistant cells, ionomycin-induced Nur77 strongly binds DNA during the first 2 h of response, in contrast to lymphoma cells treated with ionomycin together with FK506 or HA1004, which undergo massive apoptosis. We show that Nur77 could discriminate between calcium signals sensitive to FK506 and those sensitive to HA1004, as the inhibitors differentially regulate the kinetics of Nur77 nuclear import, and FK506, unlike HA1004, inhibits Nur77 DNA-binding activity. In the presence of HA1004, NBRE binding by Nur77 protein increases with time (6 h vs 2 h), whereas the final outcome of both inhibitors is apoptosis of thymic lymphoma cells

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided platinum-based 2-drug chemotherapy for unresectable nonsmall-cell lung cancer.

Science.gov (United States)

Moon, Yong Wha; Choi, Sung Ho; Kim, Yong Tai; Sohn, Joo Hyuk; Chang, Joon; Kim, Se Kyu; Park, Moo Suk; Chung, Kyung Young; Lee, Hyoun Ju; Kim, Joo-Hang

2007-05-01

The study investigated correlations between adenosine triphosphate / chemotherapy response assay (ATP-CRA) and clinical outcomes after ATP-CRA-guided platinum-based chemotherapy for unresectable nonsmall-cell lung cancer (NSCLC). The authors performed an in vitro chemosensitivity test, ATP-CRA, to evaluate the chemosensitivities of anticancer drugs such as cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and vinorelbine for chemonaive, unresectable NSCLC. The cell death rate was determined by measuring the intracellular ATP levels of drug-exposed cells compared with untreated controls. A sensitive drug was defined as a drug producing 30% or more reduction in ATP compared with untreated controls. Assay-guided platinum-based 2-drug chemotherapy was given to patients with pathologically confirmed NSCLC. Thirty-four patients were enrolled. Thirty tumor specimens were obtained by bronchoscopic biopsies and 4 obtained surgically. The median age was 61 years and 27 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The response rate was 43.8%. At a median follow-up period of 16.9 months, the median progression-free and overall survivals were 3.6 and 11.2 months, respectively. Patients were dichotomized into the platinum-sensitive (S; 20 patients) and resistant (R; 14 patients) groups. The positive/negative predictive values were 61.1% and 78.6% with a predictive accuracy of 68.8%. Although without significant differences in pretreatment parameters, the S-group showed better clinical response (P=.036), longer progression-free survival (P=.060), and longer overall survival (P=.025). Despite using bronchoscopic biopsied specimens, ATP-CRA and clinical outcomes correlated well after assay-guided platinum-based 2-drug chemotherapy for unresectable NSCLC. There was a favorable response and survival in the platinum-sensitive vs resistant groups. Copyright (c) 2007 American Cancer Society

Influence of age on the proliferation and peripheralization of thymic T cells

International Nuclear Information System (INIS)

Hirokawa, K.; Utsuyama, M.; Katsura, Y.; Sado, T.

1988-01-01

Bone marrow cells obtained from B10.Thy-1.1 mice (H-2b, Thy-1.1) were injected directly into the thymus of C57BL/6 mice (H-2b,Thy 1.2) of various ages. Thymocyte precursors in the injected donor-bone marrow cells could proliferate in the thymic microenvironment in the following manner: first, preferentially proliferating into the subcapsular cortex; and second, spreading to the whole layer of the cortex, a portion of them gradually moving into the medulla. The proliferation of donor-type thymocytes was most pronounced when intrathymic injection of bone marrow cells (ITB) was performed in newborn mice and especially prominent in week-old mice; it took approximately ten weeks for donor-type thymocytes to finish the whole course of proliferation, differentiation, and emigration to the periphery. When ITB was performed in mice 4 weeks of age and older, the proliferation of donor-type thymocytes was retarded at onset, less pronounced in magnitude, and disappeared earlier. Emigration of donor-type T cells from the thymus to the peripheral lymphoid tissues occurred most rapidly when ITB was performed in newborn mice, and these T cells continued to reside thereafter in the peripheral lymphoid tissues. However, when ITB was performed in mice 4 weeks of age and older, the number of emigrated T cells in the spleen decreased (about a tenth of that in newborn mice) and, moreover, these T cells resided only transiently in the spleen. It was suggested that T cells emigrating from the thymus of mice from newborn to 2 weeks of age are long-lived, whereas those from the thymus in mice 4 weeks of age and older are short-lived. However, when 4-week-old young adult mice were treated by irradiation or hydrocortisone, the thymic capacity was enhanced in terms of proliferation and peripheralization of thymocytes, and emigrated T cells became long-lived

Selective lymphoid irradiation. V. Synergism with pretransplant thymectomy or thymic irradiation in cardiac transplantation in rats

International Nuclear Information System (INIS)

Iga, C.; Fawwaz, R.; Nowygrod, R.; Reemtsma, K.; Hardy, M.A.

1985-01-01

Selective lymphoid irradiation (SLI) using palladium-109-hematoporphyrin (Pd-H), given four days prior to transplantation, combined with two doses of antilymphocyte globulin (ALG) (10 mg, days -2 and -1), was evaluated as a method of induction of permanent heterotopic cardiac allograft survival in the highly histoincompatible rat strain combination of ACI (RT1(1))-to-Lewis (RT1a). Both Pd-H and ALG localize poorly in the thymus, so this study evaluated whether thymic irradiation (TI) or thymectomy (TX) of the adult recipient results in indefinite allograft survival. Immunosuppression with Pd-H or ALG alone gave a mean survival time (MST) of 6.7 +/- 0.6 days, but the combination of the two agents led to an MST of 17.6 +/- 3.4 days. When TI was combined with Pd-H and ALG, cardiac allograft survival was prolonged to 50.2 +/- 13.9 days, but TI alone showed an MST of 10.3 +/- 1.8 days. Permanent cardiac allograft survival (greater than 250 days) was achieved in all thymectomized recipients treated with the combination of Pd-H and a brief course of ALG. These animals also accepted second-set skin grafts and rejected third-party skin grafts following more than 150 days of ACI cardiac allograft survival. Thymic irradiation, although effective in acting synergistically with SLI and ALG, led to prolonged, but limited allograft survival, although thymectomy with SLI and ALG is synergistic in prolonging allograft survival permanently without chronic immunosuppression

[Conversion Therapy of Initially Unresectable Rectal Cancer with Perforation via FOLFOX4 Chemotherapy].

Science.gov (United States)

Yamada, Chizu; Ishikawa, Fumihiko; Nitta, Hiroshi; Fujita, Yoshihisa; Omoto, Hideyuki; Kamata, Shigeyuki; Ito, Hiroshi

2015-11-01

We describe a case of perforated rectal cancer that became curatively resectable after FOLFOX4 chemotherapy. An 81- year-old woman was transferred to our hospital with a diagnosis of bowel perforation. She underwent emergency transverse colostomy, peritoneal lavage, and the insertion of indwelling drainage tubes, because the perforated rectal cancer was considered unresectable. After recuperation, she received chemotherapy consisting of FOLFOX4 and bevacizumab. Owing to a good response to the treatment after 4 months, rectal resection was achieved curatively. Wound dehiscence occurred as a postoperative complication. The patient chose not to receive adjuvant chemotherapy. Currently, she has been alive for more than 1 year 3 months after resection without recurrence.

A multidisciplinary treatment strategy for locally advanced rectal cancer

International Nuclear Information System (INIS)

Kimura, F.; Yanagi, Hidenori; Atono, R.

2012-01-01

The aim of this study is to examine the therapeutic effects and adverse events of preoperative chemoradiation therapy (CRT) for locally advanced rectal cancer in different radiation doses and fractions. A total of 142 consecutive patients with locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the rectum were treated with preoperative CRT and were operated radically. 121 patients with resectable cT3 or N1-2 rectal adenocarcinoma were assigned to receive pelvic radiation with single fractions of 2.5 Gy twice daily to a total dose of 25 Gy (Short CRT). Surgery was undergone within two weeks. 21 patients with clinical unresectable or marginally resectable cT4 rectal cancer were assigned to receive preoperative pelvic radiation therapy 45 to 50.4 Gy at 1.8 Gy per day. Surgery was performed 6 to 8 weeks after completion of neoadjuvant therapy (Long CRT). We examined retrospectively the preoperative therapeutic effect and adverse event of Short CRT and Long CRT. Short CRT; Overall R0 resection rate was 98%. Anus preserving rate was 95%. pCR rate was 5%. Median follow-up was 62 months. The actuarial 5-year-local-control rate was 94%. Overall survival for 5 years was 92%. Long neoadjuvant chemoradiation therapy (NCRT); Overall R0 resection rate was 90%. Anus preserving rate was 86%. pCR rate was 24%. Median follow-up was 60 months. The actuarial 5-year-local-control rate was 88%. Overall survival rate for 5 years was 88%. Radiation related adverse event such as pelvic infection and skin trouble was significantly higher in the long CRT group. Local control in primarily resectable rectal cancer after short chemoradiation was excellent. Long chemoradiation for unresectable or marginal cT4 rectum cancer was higher response ratio, but induced more radiation related adverse event than short course CRT. (author)

Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival.

Science.gov (United States)

Salem, Riad; Lewandowski, Robert J; Atassi, Bassel; Gordon, Stuart C; Gates, Vanessa L; Barakat, Omar; Sergie, Ziad; Wong, Ching-Yee O; Thurston, Kenneth G

2005-12-01

To present safety and efficacy results obtained in treatment of a cohort of patients with unresectable hepatocellular carcinoma (HCC) with use of 90Y microspheres (TheraSphere). Forty-three consecutive patients with HCC were treated with 90Y microspheres over a 4-year period. Patients were treated by liver segment or lobe on one or more occasions based on tumor distribution, liver function, and vascular flow dynamics. Patients were followed for adverse events, objective tumor response, and survival. Patients were stratified into three risk groups according to method of treatment and risk stratification (group 0, segmental; group 1, lobar low-risk; group 2, lobar high-risk) and Okuda and Child-Pugh scoring systems. Based on follow-up data from 43 treated patients, 20 patients (47%) had an objective tumor response based on percent reduction in tumor size and 34 patients (79%) had a tumor response when percent reduction and/or tumor necrosis were used as a composite measure of tumor response. There was no statistical difference among the three risk groups with respect to tumor response. Survival times from date of diagnosis were different among the risk groups (P TheraSpheres) provides a safe and effective method of treatment for a broad spectrum of patients presenting with unresectable HCC. Further investigation is warranted.

High-dose rate intra-operative radiation therapy for local advanced and recurrent colorectal cancer

International Nuclear Information System (INIS)

Harrison, L.B.; Mychalczak, B.; Enker, W.; Anderson, L.; Cohen, A.E.; Minsky, B.

1996-01-01

In an effort to improve the local control for advanced and recurrent cancers of the rectum, we have integrated high-dose rate intra-operative radiation therapy (HDR-IORT) into the treatment program. Between 11/92 and 10/95, 47 patients (pts) were treated. There were 26 males and 21 females whose ages ranged from 30-80 (median = 62) years. There were 19 pts with primary unresectable rectal cancer, and 28 pts who were treated for recurrent rectal cancer. Histology was adenocarcinoma - 45 pts, squamous cancer - 2 pts. The range of follow-up is 1-34 months (median = 14 months). The majority of primary unresectable pts received pre-operative radiation therapy (4500-5040 cGy) with chemotherapy (5-FU with Leucovorin) 4-6 weeks later, they underwent resection + HDR-IORT (1200 cGy). For the 28 pts with recurrent cancer, the majority received surgery and HDR-IORT alone because they had received prior RT. For the pts with primary unresectable disease, actuarial 2-year local control was 77%, actuarial distant metastasis-free survival was 71%, disease free survival was 66%, and overall survival was 84%. For those pts with recurrent disease, actuarial 2-year local control rate was 65%, distant metastasis-free survival was 65%, disease free survival was 47%, and overall survival was 61%. Complications occurred in 36%. There were no cases where the anatomical distribution of disease, or technical limitations prevented the adequate delivery of HDR-IORT. We conclude that this technique was most versatile, and enabled all appropriate pts to receive IORT. The preliminary data in terms of local control are encouraging, even for the poor prognostic sub-group of pts with recurrent cancer

comparison of clinical features and CT findings between atypical thymoma and thymic carcinoma

International Nuclear Information System (INIS)

Wang Xiangyang; Tan Ye; Chen Juan; Wei Jiahu; Pan Jishun; Du Jun; Zhou Cheng

2011-01-01

Objective: To investigate the differences and the similarities of clinical presentations and CT features between type B3 thymoma (atypical thymoma) and type C thymoma (thymic carcinoma) in the WHO classification of thymic epithelial tumors. Methods: Complete CT findings of thirty cases of type B3 and seventeen cases of type C thymic epithelial tumors confirmed by histopathology according to WHO 2004 Classification System and clinical features including the prognosis of each case were reviewed retrospectively. Statistical analyses of the data for the age and the long diameter were performed with Independent-Samples t test between the two groups. Statistical analysis for gender, association with myasthenia gravis, method of the operation, contours, shapes, calcification,necrosis, enhancement pattern of the tumors on CT, presence of mediastinal lymphadenopathy, invasion of mediastinal fat, chest wall, pericardium, great vessel, pleural mediastinum, metastasis to the plural, pleural effusion, distant metastasis were performed with Fisher exact test. Kaplan-Meier method was employed for survival analysis. Results: Clinical data: the average age of type B3 group was significantly younger (t=-2.905, P=0.006). 90.0% (27/30) of patients in type B3 group were complicated by myasthenia gravis, while only 5.9% (1/17) of patients in type C group were complicated by myasthenia gravis. The difference between the two groups was statistically significant (P=0.000). The ratio of complete resection of type B3 group (80.0%) was significantly higher than that in type C group (P=0.001), 70.6% (12/17) of patients in type C group died within 2 years after surgical resection, while only 20.0% (6/30) of patients in type B3 group died within one to nine years after surgical resection. Three years' survival ratio of C group was 29.4%, and five years' survival ratio of C group was lower than 14.7%, which was significantly lower than B3 group five years' survival ratio was 94.7%), which was

Unresectable Hepatocellular Carcinoma: Radioembolization Versus Chemoembolization: A Systematic Review and Meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Lobo, Laila; Yakoub, Danny; Picado, Omar; Ripat, Caroline; Pendola, Fiorella; Sharma, Rishika; ElTawil, Rana [University of Miami - Miller School of Medicine, Division of Surgical Oncology at Department of Surgery, Sylvester Comprehensive Cancer Center (United States); Kwon, Deukwoo [University of Miami - Miller School of Medicine, Department of Biostatistics and Bioinformatics, Sylvester Comprehensive Cancer Center (United States); Venkat, Shree [University of Miami - Miller School of Medicine, Department of Radiology, Sylvester Comprehensive Cancer Center (United States); Portelance, Loraine; Yechieli, Raphael, E-mail: ryechieli@med.miami.edu [University of Miami - Miller School of Medicine, Department of Radiation Oncology, Sylvester Comprehensive Cancer Center (United States)

2016-11-15

BackgroundTransarterial radioembolization (TARE) has emerged as a newer regional therapy to transarterial chemoembolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). The aim of this study is to compare clinical outcomes of both the techniques.MethodsOnline search for studies comparing TARE to TACE from 2005 to present was performed. Primary outcome was overall survival rate for up to 4 years. Secondary outcomes included post-treatment complications and treatment response. Quality of included studies was evaluated by STrengthening the Reporting of OBservational studies in Epidemiology criteria. Relative risk (RR) and 95 % confidence intervals (CI) were calculated from pooled data.ResultsThe search strategy yielded 172 studies, five met selection criteria and included 553 patients with unresectable HCC, 284 underwent TACE and 269 underwent TARE. Median ages were 63 and 64 years for TACE and TARE, respectively. Meta-analysis showed no statistically significant difference in survival for up to 4 years between the two groups (HR = 1.06; 95 % CI 0.81–1.46, p = 0.567). TACE required at least one day of hospital stay compared to TARE which was mostly an outpatient procedure. TACE had more post-treatment pain than TARE (RR = 0.51, 95 % CI 0.36–0.72, p < 0.01), but less subjective fatigue (RR = 1.68, 95 % CI 1.08–2.62, p < 0.01). There was no difference between the two groups in the incidence of post-treatment nausea, vomiting, fever, or other complications. In addition, there was no difference in partial or complete response rates between the two groups.ConclusionTARE appears to be a safe alternative treatment to TACE with comparable complication profile and survival rates. Larger prospective randomized trials, focusing on patient-reported outcomes and cost–benefit analysis are required to consolidate these results.

A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer.

Science.gov (United States)

Ben-Josef, Edgar; Schipper, Mathew; Francis, Isaac R; Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel; Simeone, Diane M; Sonnenday, Christopher; Abrams, Ross; Leslie, William; Khan, Gazala; Zalupski, Mark M

2012-12-01

Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥ 1,500/mm(3), platelets ≥ 100,000/mm(3), creatinine CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Toxicities and effects of involved-field irradiation with concurrent cisplatin for unresectable carcinoma of the pancreas

International Nuclear Information System (INIS)

Kawakami, Hiroyuki; Uno, Takashi; Isobe, Kouichi; Ueno, Naoyuki; Aruga, Takashi; Sudo, Kentaro; Yamaguchi, Taketo; Saisho, Hiromitsu; Kawata, Tetsuya; Ito, Hisao

2005-01-01

Purpose: To evaluate local effects and acute toxicities of involved field irradiation with concurrent cisplatin (CDDP) for unresectable pancreatic carcinoma. Materials and Methods: Thirty-three patients with unresectable pancreatic carcinoma were treated with chemoradiotherapy. Sixteen were Stage IVA; 17 were Stage IVB. The total prescribed dose of radiotherapy was 50 Gy/25 fractions or 50.4 Gy/28 fractions, using a three-dimensionally determined involved-field that included only the primary tumor and clinically enlarged lymph nodes. Twelve patients received a daily i.v. infusion of CDDP; 21 patients received a combination of CDDP and 5-fluorouracil either i.v. or through the proper hepatic artery. Results: Twenty-seven (82%) patients completed planned chemoradiotherapy. Nausea was the most frequent complaint. No patient experienced Grade 4 toxicities. More than half achieved pain relief. As for the primary site, only 4 patients (12%) achieved a partial response at 4 weeks; however, 3 additional patients attained >50% tumor reduction thereafter. The most frequent site of disease progression was the liver, and only 3 patients developed local progression alone. No regional lymph nodal progression outside the treatment field was seen. Median survival time and survival at 1 year were 7.1 months and 27%, respectively, for the entire group. Difference in overall survival between patients with and without distant metastases was significant (p = 0.01). Conclusions: Involved-field irradiation with concurrent daily CDDP was well tolerated without compromising locoregional effects

Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection.. Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation

Energy Technology Data Exchange (ETDEWEB)

Habermehl, D.; Lindel, K.; Rieken, S.; Haase, K.; Welzel, T.; Debus, J.; Combs, S.E. [University Hospital of Heidelberg (Germany). Dept. of Radiation Oncology; Goeppert, B.; Schirmacher, P. [Heidelberg Univ. (Germany). Inst. of Pathology; Buechler, M.W. [University Hospital of Heidelberg (Germany). Dept. of Visceral Surgery

2012-09-15

Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease. Patients and methods: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups. Results: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups. Conclusion: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials. (orig.)

Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

International Nuclear Information System (INIS)

Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

2006-01-01

Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

The petit rat (pet/pet), a new semilethal mutant dwarf rat with thymic and testicular anomalies.

Science.gov (United States)

Chiba, Junko; Suzuki, Katsushi; Suzuki, Hiroetsu

2008-12-01

The petit rat (pet/pet) is a recently discovered semilethal mutant dwarf. The neonatal pet/pet rats had a low body weight and small thymus and testis. During the first 3 d after birth, 50% of the male and 80% of the female pet/pet pups were lost or found dead. Surviving pet/pet rats showed marked retardation of postnatal growth, and their body weights were 41% (female rats) and 32% (male rats) of those of normal rats at the adult stage. The pet/pet rats exhibited proportional dwarfism, and their longitudinal bones were shorter than those of controls without skeletal malformations. Most organs of male pet/pet rats, especially the thymus, testis, adipose tissue surrounding the kidney, and accessory sex organs, weighed markedly less at 140 d of age than did those of their normal counterparts. The thymus of pet/pet rats was small with abnormal thymic follicles. Testes from pet/pet rats exhibited 2 patterns of abnormal histology. Spermatogenesis was present in testes that were only slightly anomalous, but the seminiferous tubules were reduced in diameter. In severely affected testes, most of the seminiferous tubules showed degeneration, and interstitial tissue was increased. Plasma growth hormone concentrations did not differ between pet/pet and normal male rats. The dwarf phenotype of pet/pet rats was inherited as an autosomal recessive trait. These results indicate that the pet/pet rat has a semilethal growth-hormone-independent dwarf phenotype that is accompanied by thymic and testicular anomalies and low birth weight.

Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma

International Nuclear Information System (INIS)

Wilson, L.M.; Barrington, S.F.; Kettle, A.G.; O'Doherty, M.J.; Coakley, A.J.; Morrison, I.D.

1998-01-01

The management of 38 consecutive patients with differentiated thyroid carcinoma in the period 1991-1996, who each received at least one therapy dose of iodine-131, was reviewed, looking in particular at those in whom anterior mediastinal uptake was demonstrated on scans taken 3 and 7 days post-therapy. Such activity was noted in ten patients. On the basis of clinical follow-up, thyroglobulin measurement and radiological and other scintigraphic imaging, in nine of the ten patients the anterior mediastinal activity was attributed to physiological thymic uptake. Of those nine, all were under 50 years of age; seven were considered disease free, one had residual disease in the neck and one had distant metastases. Physiological uptake by the thymus was more prominent on the 7-day scans and in patients with low tumour volumes. For appropriate patient management it is essential to recognise that physiological uptake of 131 I by the thymus in patients under 50 years of age is a potential cause of false-positive therapy scans. (orig.)

Outcomes of radioembolization for unresectable hepatocellular carcinoma in patients with marginal functional hepatic reserve.

Science.gov (United States)

Biederman, Derek M; Posham, Raghuram; Durrani, Raisa J; Titano, Joseph J; Patel, Rahul S; Tabori, Nora E; Nowakowski, Francis S; Fischman, Aaron M; Lookstein, Robert A; Kim, Edward

To evaluate the outcomes of radioembolization (RE) as a therapy for unresectable hepatocellular carcinoma (HCC) in patients with marginal functional hepatic reserve. A retrospective review of 471 patients (1/2010-7/2015) treated with RE (Therasphere, BTG, UK) was performed. A total of 36 patients (mean age: 66.1±9.3, male: 86.1%) underwent therapy for HCC with a MELD≥15 (median: 16, range: 15-22). Baseline demographics of the study cohort were as follows: etiology (HCV: 26, 72.2%), cirrhosis (n=32, 88.9%), ECOG 0 (n=16, 44.4%), Child-Pugh class (A=15, B=19, C=2), unilobar distribution (n=27, 75%), AFP>200 (n=11, 30.6%), portal vein thrombosis (PVT, n=7, 19.4%), metastasis (n=3, 8.3%). Outcomes analyzed included CTCAEv4.03 laboratory toxicities (120-day), imaging response (mRECIST), progression-free survival (PFS), and overall survival (OS). A total of 42 treatments were performed with mean dose of 2.02±1.23GBq. The cumulative grade 3/4 toxicity was 28% overall and 21% for bilirubin at 120-days. The objective response and disease control rates were 48.3% (14/29) and 69% (20/29) respectively. The median (95% CI) PFS was 5.9 (4.4-7.7) months. Ten (27.8%) patients received additional locoregional therapy at a median (IQR) of 138 (102-243) days post RE. The mean (95% CI) OS was 21.9 (14.8-29.0) months. The absence of PVT was associated with improved OS (p=0.005) Disease control at 90-days was also associated with an OS benefit (p=0.037). Patients with unresectable HCC and marginal functional hepatic reserve treated with RE had favorable objective response and disease control rates, both predictive of overall survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired Thymic Output in Patients with Chronic Hepatitis C Virus Infection

DEFF Research Database (Denmark)

Hartling, Hans Jakob; Gaardbo, Julie Christine; Ronit, Andreas

2013-01-01

Altered T cell homeostasis in chronic hepatitis C virus (HCV) infection has been demonstrated. However, it is unknown if fibrosis is associated with more perturbed T cell homeostasis in chronic HCV infection. The aim of the present study was to examine and compare T cell subsets including recent...... thymic emigrants (RTE), naive, memory, senescent, apoptotic and IL-7 receptor α (CD127) expressing CD4+ and CD8+ T cells as well as telomere length and interferon-γ production in HCV-infected patients with (n=25) and without (n=26) fibrosis as well as in healthy controls (n=24). Decreased proportions...... of CD4+ and CD8+ RTE were found in HCV-infected patients, especially in HCV-infected patients with fibrosis (14.3% (9.7-23.0) and 28.8% (16.1-40.5), respectively) compared to healthy controls (24.2% (16.3-32.1), P=0.004, and 39.1% (31.6-55.0), P=0.010, respectively). Furthermore, HCV-infected patients...

Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis

Energy Technology Data Exchange (ETDEWEB)

Demizu, Yusuke, E-mail: y_demizu@nifty.com [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Jin, Dongcun; Sulaiman, Nor Shazrina; Nagano, Fumiko; Terashima, Kazuki; Tokumaru, Sunao [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Akagi, Takashi [Department of Radiation Physics, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Fujii, Osamu [Department of Radiation Oncology, Hakodate Goryokaku Hospital, Hakodate, Hokkaido (Japan); Daimon, Takashi [Department of Biostatistics, Hyogo College of Medicine, Nishinomiya, Hyogo (Japan); Sasaki, Ryohei [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Fuwa, Nobukazu [Department of Radiation Oncology, Ise Red Cross Hospital, Ise, Mie (Japan); Okimoto, Tomoaki [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan)

2017-06-01

Purpose: To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. Methods and Materials: From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). Results: The median patient age was 67 years (range 18-87). The median planning target volume (PTV) was 455 cm{sup 3} (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm{sup 3} were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm{sup 3} were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P<.001). Conclusions: Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic. Nevertheless, a

NK cell activite in C157BL/Ka mice during the development of radiation induced thymic lymphomas

International Nuclear Information System (INIS)

Noel, A.; Schaaf-Lafontaine, N.; Defresne, M.P.; Boniver, J.

1985-01-01

Treatment of C57BL/Ka mice with a split dose whole-body irradiation (four weekly irradiations of 1,75 Gy) induces the development of thymic lymphomas. NK activity of spleen cells has been determined at several internals after leukemogenic treatment. Two days after irradiations, NK activity is normal and decreases strongly after one week. This period of decline persists during about one month. Then, NK activity restores and reaches control values. Lymphomas appear in spite of NK activity restauration. The diminution of NK activity during the preleukemic period could favour preleukemic cells apparition [fr

Hyperfractionated Radiotherapy with Concomitant Boost Technique for Unresectable Non-Small Cell Carcinoma of the Lung

International Nuclear Information System (INIS)

Chun, Ha Chung; Lee, Myung Za

1991-01-01

Twenty five patients with unresectable non-small cell carcinoma of the lung have been treated with hyperfractionated radiotherapy with concomitant boost technique since September, 1989. Those patients with history of previous surgery or chemotherapy, pleural effusion or significant weight loss (greater than 10% of body weight) were excluded from the study. Initially, 27 Gy were delivered in 15 fractions in 3 weeks to the large field. Thereafter, large field received 1.8 Gy and cone down boost field received 1.4Gy with twice a day fractinations up to 49.4Gy. After 49.4Gy, only boost field was treated twice a day with 1.8 and 1.4 Gy. Total tumor doses were 62.2Gy for 12 patients and 65.4Gy for remaining 13 patients. Follow up period was ranged from 6 to 24 month. Actuarial survival rates at 6, 12, and 18 month were 88%, 62%, and 38%, respectively. Corresponding disease free survival rates were 88%, 41%, and 21%, respectively. Actuarial cumulative local failure rates at 9,12 and 15 month were 36%, 42%, and 59%, respectively. No significant increase of acute or late complications including radiation pneumonitis was noted with maximum follow up of 24 month. Although the longer follow up is needed, it is worthwhile to try the prospective randomized study to evaluate the efficacy of hyperfractionated radiotherapy with concomitant boost technique for unresectable non-small cell lung cancers in view of excellent tolerance of this treatment. In the future, further increase of total radiation dose might be necessary to improve local control for non-small cell lung cancer

Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Kawaoka, Tomokazu; Aikata, Hiroshi; Takaki, Shintaro; Katamura, Yoshio; Hiramatsu, Akira; Waki, Koji; Takahashi, Shoichi; Hieda, Masashi; Toyota, Naoyuki; Ito, Katsuhide; Chayama, Kazuaki

2009-01-01

We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0-67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10-390 mg). Survival rates were 86% at 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.

Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation.

Science.gov (United States)

Kulik, Laura M; Atassi, Bassel; van Holsbeeck, Lodewijk; Souman, Tameem; Lewandowski, Robert J; Mulcahy, Mary F; Hunter, Russell D; Nemcek, Albert A; Abecassis, Michael M; Haines, Kenneth G; Salem, Riad

2006-12-01

To present the clinical data of 35 patients with T3 unresectable hepatocellular carcinoma (HCC) that were treated with (90)Y with the specific intent of downstaging to resection, radiofrequency ablation (RFA) candidate, United Network for Organ Sharing (UNOS) stage T2 or liver transplantation. One hundred fifty patients with unresectable HCC were treated with (90)Y microspheres. Of these, 35 patients were UNOS stage T3 at the time of treatment. Patients were followed for clinical toxicities, alterations in model for end-stage-liver disease (MELD) score, tumor response, downstaging to RFA, resection, transplantation, and survival. Nineteen of 34 patients (56%) were successfully downstaged from T3 to T2 following treatment. 11 of 34 (32%) patients treated were downstaged to target lesions measuring 3.0 cm or less. Twenty-three of 35 (66%) were downstaged to either T2 status, lesion < 3.0 cm (RFA candidate), or resection. Seventeen of 34 (50%) had an objective tumor response by WHO criteria. Eight patients (23%) were successfully downstaged and underwent OLT following treatment. 1, 2, and 3-year survival was 84%, 54%, and 27%, respectively. Median survival by Kaplan-Meier analysis for the entire cohort was 800 days. These data suggest that intra-arterial (90)Y microspheres can be used as a bridge to transplantation, surgical resection, or RFA. (c) 2006 Wiley-Liss, Inc.

Pilot study of a novel, large-bore, fully covered self-expandable metallic stent for unresectable distal biliary malignancies.

Science.gov (United States)

Mukai, Tsuyoshi; Yasuda, Ichiro; Isayama, Hiroyuki; Iwashita, Takuji; Itoi, Takao; Kawakami, Hiroshi; Kogure, Hirofumi; Nakai, Yousuke

2016-09-01

In patients with unresectable malignant distal biliary obstruction, covered self-expandable metallic stents (CSEMS) may remain patent longer than uncovered self-expandable metallic stents as a result of tumor ingrowth prevention. One main cause of recurrent biliary obstruction (RBO) in CSEMS is sludge formation, which can be prevented using a large-bore stent. Therefore, we developed a novel, 12-mm diameter fully covered SEMS (FCSEMS) and investigated its clinical safety, efficacy, and rate of adverse events. This prospective, multicenter pilot study, which ran between June 2011 and November 2012, included 38 consecutive patients with unresectable malignant distal biliary obstruction. All patients underwent endoscopic insertion of our novel stent. Primary endpoint was non-RBO rate 6 months after placement. Technical and functional success rates of the procedures were 100%. Six-month non-RBO rate was 50%, and median time to RBO was 184 days. Median survival time was 241 days. Twelve patients died within 6 months after stent placement without RBO. RBO was observed in 10 patients (26%), with seven experiencing stent occlusion and three experiencing stent migration. Adverse events other than RBO (at Stent removal for reintervention was successfully completed in eight patients. Our novel FCSEMS may be safe and effective for managing malignant distal obstruction with an acceptable incidence of adverse events. © 2016 Japan Gastroenterological Endoscopy Society.

Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden

Directory of Open Access Journals (Sweden)

Morgan Gareth

2011-06-01

Full Text Available Abstract Background The study exploits a natural human experimental model of subsistence farmers experiencing chronic and seasonally modified food shortages and infectious burden. Two seasons existed, one of increased deprivation and infections (Jul-Dec, another of abundance and low infections (Jan-Jun; referred to as the hungry/high infection and harvest/low infection seasons respectively. Prior analysis showed a 10-fold excess in infectious disease associated mortality in young adults born in the hungry/high infection versus harvest/low infection season, and reduced thymic output and T cell counts in infancy. Here we report findings on the role of early life stressors as contributors to the onset of T cell immunological defects in later life. Methods We hypothesised that season of birth effects on thymic function and T cell immunity would be detectable in young adults since Kaplan-Meier survival curves indicated this to be the time of greatest mortality divergence. T cell subset analyses by flow-cytometry, sjTRECs, TCRVβ repertoire and telomere length by PCR, were performed on samples from 60 males (18-23 y selected to represent births in the hungry/high infection and harvest/low infection Results Total lymphocyte counts were normal and did not differ by birth season. CD3+ and CD4+ but not CD8+ counts were lower for those born during the hungry/high infection season. CD8+ telomere length also tended to be shorter. Overall, CD8+ TCRVβ repertoire skewing was observed with 'public' expressions and deletions seen in TCRVβ12/22 and TCRVβ24, respectively but no apparent effect of birth season. Conclusions We conclude that, although thymic function was unchanged, the CD4+ and CD3+ counts, and CD8+ telomere length results suggested that aspects of adult T cell immunity were under the influence of early life stressors. The endemicity of CMV and HBV suggested that chronic infections may modulate immunity through T cell repertoire development. The

The Analysis of the Causes of Prolonged Hospitalization after Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Chang, Nam Kyu; Jeong, Yong Yeon; Park, Seo Yeon; Kim, Jae Kyu

2011-01-01

We wanted to analyze the causes of prolonged hospitalization (over 7 days) after transarterial chemoembolization (TACE) in patients with unresectable Hepatocellular Carcinoma and its related factors. We analyzed the total hospital days after patients with unresectable Hepatocellular Carcinoma received transarterial chemoembolization, and these patients were treated during the recent 6 month at our hospital. Two hundred twenty three sessions showed a short term hospital stay (less than 7 days) and 57 sessions showed a prolonged hospital stay (more than 7 days), so a total of 280 sessions were analyzed. The hospital stay less than seven days was set for the control group and this was correlated with the patient's age, gender, the level of bilirubin and albumin, the platelet counts, the AST/ALT ratio, the a-FT, the presence of portal vein thrombosis and ascites, several scoring systems (Child-Pugh, CLIP, and OKUDA score) and the need for additional embolization at the time of the procedure. Compared with that of the control group, ascites (p=0.004), portal vein thrombosis (p=0.000), a platelet count below the hundred thousand (p=0.012), a Child-Pugh score more than B (p=0.023), a CLIP score more than 2 (p=0.000) and a OKUDA score more than II (p=0.000) showed significant differences. The evaluation of patients' factors would be useful to predict extended post-procedural hospitalization after hepatic chemoembolisation

Nutritional factors as predictors of response to radio-chemotherapy and survival in unresectable squamous head and neck carcinoma

International Nuclear Information System (INIS)

Salas, Sebastien; Deville, Jean-Laurent; Giorgi, Roch; Pignon, Thierry; Bagarry, Danielle; Barrau, Karine; Zanaret, Michel; Giovanni, Antoine; Bourgeois, Aude; Favre, Roger; Duffaud, Florence

2008-01-01

Background and purpose: This study sought to evaluate nutritional prognostic factors before treatment in patients with unresectable head and neck cancer treated by concomitant radio-chemotherapy. Methods and materials: Seventy-two consecutive patients were treated. We studied the potential effects of CRP, Alb, preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier estimates, and curves were compared using the log-rank test. Results: All biological nutritional factors were statistically correlated with the response to radio-chemotherapy. In multivariate analysis, only CRP (p = 0.004) remained statistically significant. A statistical correlation was found between Alb and EFS in multivariate analysis (p = 0.04). The factors influencing OS in univariate analysis were Alb (p = 0.008), CRP (p = 0.004), orosomucoid (p = 0.01) and NRI (p = 0.01), response to radio-chemotherapy (p < 0.001) and staging (p = 0.04). In multivariate analysis, only the response to radio-chemotherapy (p < 0.001) remained significant. Conclusions: This study illustrates the prognostic value of nutritional status. CRP and Alb may be useful in the assessment of advanced head and neck cancer patients at diagnosis and for stratifying patients taking part in randomized trials

Unique loss of heterozygosity of murine thymic lymphomas as a candidate of radiation signature

Energy Technology Data Exchange (ETDEWEB)

Shimada, Yoshiya; Nishimura, Mayumi; Kakinuma, Shizuko [National Inst. of Radiological Sciences, Chiba (Japan); Wakana, Shigeharu; Okumoto, Masaaki

1999-06-01

Signature(s) of prior exposure to carcinogens have immediate application to the identification of environmental risk factors. Such signatures have been sought to aid in developing policies for the protection from risks of environmental carcinogens. Although ionizing radiation is a potent carcinogenic agent, little is known about possible radiation signatures. This is because radiation induces a broad spectrum of DNA lesions. Here we describe a diversity of K-ras mutations and a unique locus with frequent loss of heterozygisity (LOH) on chromosome 11 of radiation induced thymic lymphomas. The latter locus has never been observed to be similarly altered in either ethylnitrosourea-induced or spontaneously developed lymphomas. These results describe, to our knowledge for the first time, a molecular basis for radiation signature. (author)

IL-4/IL-13 Signaling Inhibits the Potential of Early Thymic Progenitors To Commit to the T Cell Lineage.

Science.gov (United States)

Barik, Subhasis; Miller, Mindy M; Cattin-Roy, Alexis N; Ukah, Tobechukwu K; Chen, Weirong; Zaghouani, Habib

2017-10-15

Early thymic progenitors (ETPs) are endowed with diverse potencies and can give rise to myeloid and lymphoid lineage progenitors. How the thymic environment guides ETP commitment and maturation toward a specific lineage remains obscure. We have previously shown that ETPs expressing the heteroreceptor (HR) comprising IL-4Rα and IL-13Rα1 give rise to myeloid cells but not T cells. In this article, we show that signaling through the HR inhibits ETP maturation to the T cell lineage but enacts commitment toward the myeloid cells. Indeed, HR + ETPs, but not HR - ETPs, exhibit activated STAT6 transcription factor, which parallels with downregulation of Notch1, a critical factor for T cell development. Meanwhile, the myeloid-specific transcription factor C/EBPα, usually under the control of Notch1, is upregulated. Furthermore, in vivo inhibition of STAT6 phosphorylation restores Notch1 expression in HR + ETPs, which regain T lineage potential. In addition, upon stimulation with IL-4 or IL-13, HR - ETPs expressing virally transduced HR also exhibit STAT6 phosphorylation and downregulation of Notch1, leading to inhibition of lymphoid, but not myeloid, lineage potential. These observations indicate that environmental cytokines play a role in conditioning ETP lineage choice, which would impact T cell development. Copyright © 2017 by The American Association of Immunologists, Inc.

Activation of the aryl hydrocarbon receptor reduces the number of precursor and effector T cells, but preserves thymic CD4(+)CD25(+)Foxp3(+) regulatory T cells

NARCIS (Netherlands)

Schulz, V.J.; Smit, J.J.; Bol-Schoenmakers, M.; van Duursen, M.B.M.; van den Berg, M.; Pieters, R.H.H.

2012-01-01

Aryl hydrocarbon receptor (AhR) activation suppresses immune responses, including allergic sensitization, by increasing the percentage of regulatory (Treg) cells. Furthermore, AhR activation is known to affect thymic precursor T cells. However, the effect of AhR activation on intrathymic

Origins and Properties of Dental, Thymic, and Bone Marrow Mesenchymal Cells and Their Stem Cells

Science.gov (United States)

Komada, Yukiya; Yamane, Toshiyuki; Kadota, Daiji; Isono, Kana; Takakura, Nobuyuki; Hayashi, Shin-Ichi; Yamazaki, Hidetoshi

2012-01-01

Mesenchymal cells arise from the neural crest (NC) or mesoderm. However, it is difficult to distinguish NC-derived cells from mesoderm-derived cells. Using double-transgenic mouse systems encoding P0-Cre, Wnt1-Cre, Mesp1-Cre, and Rosa26EYFP, which enabled us to trace NC-derived or mesoderm-derived cells as YFP-expressing cells, we demonstrated for the first time that both NC-derived (P0- or Wnt1-labeled) and mesoderm-derived (Mesp1-labeled) cells contribute to the development of dental, thymic, and bone marrow (BM) mesenchyme from the fetal stage to the adult stage. Irrespective of the tissues involved, NC-derived and mesoderm-derived cells contributed mainly to perivascular cells and endothelial cells, respectively. Dental and thymic mesenchyme were composed of either NC-derived or mesoderm-derived cells, whereas half of the BM mesenchyme was composed of cells that were not derived from the NC or mesoderm. However, a colony-forming unit-fibroblast (CFU-F) assay indicated that CFU-Fs in the dental pulp, thymus, and BM were composed of NC-derived and mesoderm-derived cells. Secondary CFU-F assays were used to estimate the self-renewal potential, which showed that CFU-Fs in the teeth, thymus, and BM were entirely NC-derived cells, entirely mesoderm-derived cells, and mostly NC-derived cells, respectively. Colony formation was inhibited drastically by the addition of anti-platelet–derived growth factor receptor-β antibody, regardless of the tissue and its origin. Furthermore, dental mesenchyme expressed genes encoding critical hematopoietic factors, such as interleukin-7, stem cell factor, and cysteine-X-cysteine (CXC) chemokine ligand 12, which supports the differentiation of B lymphocytes and osteoclasts. Therefore, the mesenchymal stem cells found in these tissues had different origins, but similar properties in each organ. PMID:23185234

Chemoradiotherapy for lung cancer. Current status and perspectives

International Nuclear Information System (INIS)

Ohe, Yuichiro

2004-01-01

For many years, thoracic radiotherapy had been regarded as the standard treatment for patients with unresectable locally advanced non-small cell lung cancer. However, meta-analyses show that cisplatin-containing chemoradiotherapy is significantly superior to radiotherapy alone in terms of survival. Moreover, concurrent chemoradiotherapy yields a significantly increased response rate and enhanced survival duration when compared with the sequential approach. Cisplatin-based chemotherapy with concurrent thoracic radiotherapy yields a 5-year survival rate of approximately 15% for patients with unresectable locally advanced non-small cell lung cancer. The state-of-the-art treatment for limited-stage small cell lung cancer is considered to be four cycles of combination chemotherapy with cisplatin plus etoposide combined with early concurrent twice-daily thoracic irradiation (45 Gy). If patients achieve complete remission, prophylactic cranial irradiation should be administered. A 5-year survival rate of approximately 25% is expected with the state-of-the-art treatment for limited-stage small cell lung cancer. Chemoradiotherapy is considered to be a standard treatment for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. Several new strategies are currently being investigated to improve the survival of these patients. The incorporation of target-based drugs such as gefitinib is considered to be the most promising strategy for unresectable locally advanced non-small cell lung cancer. The incorporation of irinotecan is also a promising strategy to improve the survival of patients with limited-stage small cell lung cancer. The Japan Clinical Oncology Group is conducting clinical trials to develop new treatment strategies for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. (author)

Unresectable colorectal liver metastases. Percutaneous ablation using CT-guided high-dose-rate brachytherapy (CT-HDBRT); Nicht resektable kolorektale Lebermetastasen. Perkutane Ablation mittels CT-gesteuerter Hochdosisbrachytherapie (CT-HDBRT)

Energy Technology Data Exchange (ETDEWEB)

Collettini, F.; Lutter, A.; Schnapauff, D.; Denecke, T.; Gebauer, B. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of Diagnostic and Interventional Radiology; Hildebrandt, B. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of Oncology; Puhl, G. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of General, Visceral and Transplantation Surgery; Wust, P. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of Radiation Oncology

2014-06-15

Purpose: To evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) of unresectable colorectal liver metastases (CRLMs). Materials and Methods: Retrospective analysis of all consecutive patients with unresectable CRLMs treated with CT-HDRBT between January 2008 and November 2012. Treatment was performed by CT-guided catheter placement and high-dose-rate brachytherapy with an iridium-192 source. MRI follow-up was performed after 6 weeks and then every 3 months post-intervention. The primary endpoint was local tumor control (LTC); secondary endpoints included time to progression (TTP) and overall survival (OS). Results: 80 heavily pretreated patients with 179 metastases were available for MRI evaluation for a mean follow-up time of 16.9 months. The mean tumor diameter was 28.5 mm (range: 8 - 107 mm). No major complications were observed. A total of 23 (12.9%) local tumor progressions were observed. Lesions ≥ 4 cm in diameter showed significantly more local progression than smaller lesions (< 4 cm). 50 patients (62.5%) experienced systemic tumor progression. The median TTP was 6 months. 28 (43%) patients died during the follow-up period. The median OS after ablation was 18 months. Conclusion: CT-HDRBT is an effective technique for the treatment of unresectable CRLMs and warrants promising LTC rates compared to thermal ablative techniques. A combination with other local and systemic therapies should be evaluated in patients with lesions > 4 cm in diameter, in which higher progression rates are expected. (orig.)

Mediastinal neoplasms in patients with Graves disease: a possible link between sustained hyperthyroidism and thymic neoplasia?

Directory of Open Access Journals (Sweden)

Boyd Jonathan D

2012-07-01

Full Text Available Abstract Background Anterior mediastinal masses are a rare but well documented finding in Graves disease. The vast majority of these lesions represents benign thymic hypertrophy and regress after treatment of the hyperthyroidism. A small percentage of these cases however represent neoplastic/malignant diseases which require further treatment. Cases 12 year old boy with one year history of refractory Graves disease was found to have an anterior mediastinal mass and underwent curative thyroidectomy for sustained hyperthyroidism. Cervical lymphadenopathy was detected during the procedure and biopsy was obtained. A 23 year old woman who presented with a one month history of hyperthyroid symptoms, was diagnosed with Graves disease and also was found to have an anterior mediastinal mass on imaging. Biopsy of the anterior mediastinal mass was obtained and subsequently the patient underwent robotic thymectomy. Histologic examination and immunophenotyping of the cervical lymph node in a 12 year old boy revealed neoplastic proliferation of T lymphoblasts diagnostic of T lymphoblastic leukemia/lymphoma. Examination of the anterior mediastinal mass biopsy in the 23 year old woman revealed type B1 thymoma which was confirmed after examination of the subsequent robotic thymectomy specimen. Conclusion This is the first reported case of T cell lymphoblastic lymphoma and the third reported case of thymoma associated with sustained hyperthyroidism due to Graves disease. These cases indicate that an anterior mediastinal mass in a patient with active Graves disease may be due to a neoplastic cause, which may require definitive treatment. Caution should be exercised when dismissing a mediastinal mass as benign thymic hyperplasia in patients with active Graves disease.

Differential regulation of caspase-9 by ionizing radiation- and UV-induced apoptotic pathways in thymic cells

Energy Technology Data Exchange (ETDEWEB)

Okamoto, Mayumi; Koga, Satomi [Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima 727-0023 (Japan); Tatsuka, Masaaki, E-mail: tatsuka@pu-hiroshima.ac.jp [Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima 727-0023 (Japan)

2010-06-01

In mouse thymic lymphoma 3SB cells bearing wild type p53, ionizing radiation (IR) and UV light are potent triggers of caspase-3-dependent apoptosis. Although cytochrome c was released from mitochondria as expected, caspase-9 activation was not observed in UV-exposed cells. Laser scanning confocal microscopy analysis showed that caspase-9 is localized in an unusual punctuated pattern in UV-induced apoptotic cells. In agreement with differences in the status of caspase-9 activation between IR and UV, subcellular protein fractionation experiments showed that pro-apoptotic apoptosis protease-activating factor 1 (Apaf-1), normally a part of the apoptosome assembled in response to the release of cytochrome c from mitochondria, and B-cell lymphoma extra long (Bcl-xL), an inhibitor of the change in mitochondrial membrane permeability, were redistributed by the IR-exposure but not by the UV-exposure. Instead of the sequestration of the capase-9/apoptosome activation in UV-induced apoptotic cells, the extrinsic apoptotic signaling generated by caspase-8 activation and consequent activation of B-cell lymphoma extra long (Bid) to release cytochrome c from mitochondria was observed. Thus, the post-mitochondrial apoptotic pathway downstream of cytochrome c release cannot operate the apoptosome function in UV-induced apoptosis in thymic 3SB cells. The intracellular redistribution and sequestration of apoptosis-related proteins upon mitochondrion-based apoptotic signaling was identified as a novel cellular mechanism to respond to DNA damage in an agent type-specific manner. This finding suggests that the kind of the critical ultimate apoptosis-inducing DNA lesion complex form resulting from the agent-specific DNA damage responses is important to determine which of apoptosis signals would be activated.

Evaluation of multimodality treatment for advanced pancreatic cancer. Special reference to intraoperative vs. external radiation therapy

International Nuclear Information System (INIS)

Wakasugi, Hideyuki; Funakoshi, Akihiro; Seo, Yousuke; Iguchi, Haruo; Wada, Susumu

1999-01-01

Intraoperative radiation therapy (IORT)+postoperative external beam radiation therapy (ERT) with chemotherapy and ERT alone with chemotherapy have been performed in our hospital for unresectable, especially locally advanced, pancreatic cancer. We compared the former method with the latter. Chemotherapy was performed together with radiation, using 5-FU, CDDP, and MMC. IORT+ERT was successful in only half of the treated patients, while ERT alone was successful in almost all of the patients. As a result, the doses of radiation were often shorter in patients treated by the former method compared to the latter method. Both methods, when completed for locally advanced pancreatic cancer (stage IVa), produced good effects on tumor markers, tumor size and pain. Furthermore, the latter method was better than the former in improving the survival time and quality of life (QOL). Therefore, ERT is a practical and useful method for patients with locally advanced pancreatic cancer. (author)

Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk

DEFF Research Database (Denmark)

Jeppesen, Dorthe Lisbeth; Hasselbalch, H; Ersbøll, A K

2003-01-01

/weight-ratio (Ti/w) at birth and at 4 mo of age in 12 healthy uninfected infants born to HlV-infected mothers. All infants were exclusively fed pasteurized donor milk. The results were compared with those obtained from a previous cohort of exclusively breastfed, partially breastfed and exclusively formula.......8 and the mean Ti/w-ratio was 4.2. Compared with those of exclusively breastfed infants, the Ti and Ti/w-ratio of infants fed donor milk were significantly reduced (p infants compared with that in the formula-fed infants (p = 0.02). CONCLUSION: At birth...... with thymic size in infants that were exclusively formula fed....

BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES.

Science.gov (United States)

Torres, Orlando Jorge Martins; Marques, Márcio Carmona; Santos, Fabio Nasser; Farias, Igor Correia de; Coutinho, Anelisa Kruschewsky; Oliveira, Cássio Virgílio Cavalcante de; Kalil, Antonio Nocchi; Mello, Celso Abdon Lopes de; Kruger, Jaime Arthur Pirola; Fernandes, Gustavo Dos Santos; Quireze, Claudemiro; Murad, André M; Silva, Milton José de Barros E; Zurstrassen, Charles Edouard; Freitas, Helano Carioca; Cruz, Marcelo Rocha; Weschenfelder, Rui; Linhares, Marcelo Moura; Castro, Leonaldson Dos Santos; Vollmer, Charles; Dixon, Elijah; Ribeiro, Héber Salvador de Castro; Coimbra, Felipe José Fernandez

2016-01-01

In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization. RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

Meta[{sup 131}I]iodobenzylguanidine therapy for patients with metastatic and unresectable pheochromocytoma and paraganglioma

Energy Technology Data Exchange (ETDEWEB)

Goldsby, Robert E. [Division of Pediatric Oncology, Department of Pediatrics, University of California, San Francisco, CA 94143-0106 (United States); Fitzgerald, Paul A. [Division of Endocrinology, Department of Medicine, University of California, San Francisco, CA 94143-1222 (United States)], E-mail: paul.fitzgerald@ucsf.edu

2008-08-15

Introduction: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are tumors that can exhibit a malignant behavior. Targeted radiotherapy with {sup 131}I-metaiodobenzylguanidine ({sup 131}I-MIBG) has proven useful in patients with unresectable, metastatic and/or relapsed disease. Methods: We review the literature and our experience at UCSF to highlight important characteristics of PHEO/PGL and the use of {sup 131}I-MIBG in the treatment of this disease. Results: These tumors are rare, with a diagnosed incidence of only two to four cases per million annually; 40% are discovered at autopsy. Clinical manifestations are caused by excess secretion of catecholamines, although some PGLs are nonsecretory. Approximately 25% of patients with PHEO/PGLs have an underlying genetic predisposition. The risk of a germline mutation is higher in children. Diagnostic evaluation should include serial determinations of fractionated metanephrines and serum chromogranin A. Staging requires both {sup 123}I-MIBG and full-body magnetic resonance imaging or {sup 18}FDG-PET scanning. The primary treatment for PHEO/PGL is resection. Patients may be candidates for treatment with {sup 131}I-MIBG if they have unresectable or metastatic tumors that are avid for MIBG. Such patients usually respond to this targeted radioisotope therapy and many achieve a durable remission. Myelosuppression is a dose-related side effect that can be treated with transfusions or autologous hematopoietic stem cells. Late side effects can include infertility, myelodysplasia and second cancers. Conclusions: Treatment with {sup 131}I-MIBG can be considered for patients if surgery is not feasible. There are significant risks associated with this treatment, but the majority of patients will respond. Treatment with {sup 131}I-MIBG should be done at institutions with experience in delivering targeted radiotherapeutics.

Signal transduction around thymic stromal lymphopoietin (TSLP in atopic asthma

Directory of Open Access Journals (Sweden)

Kuepper Michael

2008-08-01

Full Text Available Abstract Thymic stromal lymphopoietin (TSLP, a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs. DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa. These different cells secrete inflammatory cytokines and chemokines operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus, involved in the control of both an innate and an adaptive immune response. Since TSLP links contact of allergen with the airway epithelium to the onset and maintainance of the asthmatic syndrome, defining the signal transduction underlying TSLP expression and function is of profound interest for a better understandimg of the disease and for the development of new therapeutics.

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver.

Science.gov (United States)

de Leede, Eleonora M; Burgmans, Mark C; Martini, Christian H; Tijl, Fred G J; van Erkel, Arian R; Vuyk, Jaap; Kapiteijn, Ellen; Verhoef, Cornelis; van de Velde, Cornelis J H; Vahrmeijer, Alexander L

2016-07-31

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials.

Directory of Open Access Journals (Sweden)

Ping Fang

Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. METHODS: PubMed, the Cochrane Library, and Google Scholar were searched using the terms "bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable". Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS, tumor response, and toxicities. RESULTS: A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial or in combination with erlotinib (n = 4 trials, capecitabine (n = 1 trial, capecitabine+oxaliplatin (n = 1 trial, or gemcitabine+oxaliplatin (n = 1 trial. Most trials (five of eight reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%, fatigue (12%, hypertension (10%, diarrhea (8%, and neutropenia (5%. Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12, typically due to esophageal varices. CONCLUSIONS: Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently

Living Donor Liver Transplantation for Unresectable Liver Adenomatosis Associated with Congenital Absence of Portal Vein: A Case Report and Literature Review

OpenAIRE

Brasoveanu, Vladislav; Ionescu, Mihnea Ioan; Grigorie, Razvan; Mihaila, Mariana; Bacalbasa, Nicolae; Dumitru, Radu; Herlea, Vlad; Iorgescu, Andreea; Tomescu, Dana; Popescu, Irinel

2015-01-01

Patient: Female, 21 Final Diagnosis: Unresectable liver adenomatosis associated with congenital absence of portal vein Symptoms: — Medication: — Clinical Procedure: Living donor liver transplantation Specialty: Transplantology Objective: Rare disease Background: Abernethy malformation (AM), or congenital absence of portal vein (CAPV), is a very rare disease which tends to be associated with the development of benign or malignant tumors, usually in children or young adults. Case Report: We rep...

Appearance of thymic nurse cells after gamma irradiation

International Nuclear Information System (INIS)

Mulder, A.H.; Bekkum, D.W. van

1983-01-01

Since prothymocytes home from the bone marrow to the thymus, it was tested in the mouse whether prothymocytes could be recaptured from thymic nurse cells (TNC). Bone marrow cells were labelled with the red fluorescing anthracycline daunomycin and varying numbers (up to 25 x 10 6 nucleated bone marrow cells) were injected into lethally irradiated recipients. At several time intervals after transplantation (up to 24 hours), thymuses were removed and the TNCs were isolated. No specific red fluorescence was found within the TNCs. These experiments were repeated with supravital compounds at concentrations which have been shown not to affect viability, homing pattern and function. Again, no specific fluoresence was found in the TNC after transplantation of labelled bone marrow into irradiated mice. The relationship between the dose of total body gamma irradiation and the time after irradiation was investigated. Maximal numbers of TNCs were found at 6 hours after irradiation with 4 Gy. Eight to 12 hours after irradiation, the number of TNCs isolated decreased and had returned to preirradiation levels at 24 hours. The relation between TBI dose and the number of TNCs per thymus is shown. The number determined at 3 hours increased with the dose to reach a maximum at 4 Gy. The authors later studied the morphology of the TNCs isolated at 4 to 6 hours after irradiation. On electron microscopic examination, signs of degeneration and death of the enclosed thymocytes was detected. (Auth.)

Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or Recurrent Malignant Peripheral Nerve Sheath Tumor

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0115 TITLE: Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or...Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited REPORT DOCUMENTATION PAGE Form...Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time

Intraoperative radio-frequency capacitive hyperthermia and radiation therapy for unresectable pancreatic cancer

International Nuclear Information System (INIS)

Nakazawa, M.; Yamashita, T.; Hashida, I.

1988-01-01

The authors have initiated intraoperative radiation therapy (IORT) and intraoperative radio-frequency capacitive hyperthermia (IOHT) for unresectable pancreatic cancer. After gastric (corpus) resection, IORT and IOHT were conducted and gastro-duodenostomy was performed IORT was delivered with 12 meV electron (25 Gy) and 10 MV Linac x-ray (7.5 Gy). IOHT was done with 13.56 MHz capacitive equipment aiming 43 0 C for over 30 min along with concurrent administration of 500 mg 5-FU. Five cases were heated by the conventional method and two additional cases were heated with a newly fabricated applicator. Attained temperatures monitored directly from tumor were 38.5 0 C-44.3 0 C (over 43 0 C in four cases, 40 0 C in one case, and below 40 0 C in two cass.) Pain relief was achieved in most cases. Using the new applicators, the authors could avoid unexpected hot spots and insufficient heating

Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

Energy Technology Data Exchange (ETDEWEB)

Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.jp [Department of Radiology, University of the Ryukyus, Okinawa (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center, Tokyo (Japan); Hirokawa, Naoki [Department of Radiology, Sapporo Medical University, Sapporo (Japan); Shibuya, Keiko [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto (Japan); Kokubo, Masaki [Department of Radiation Oncology, Institute of Biomedical Research and Innovation Hospital, Kobe (Japan); Ogo, Etsuyo [Department of Radiation Oncology, Kurume University, Kurume (Japan); Shibuya, Hitoshi [Department of Radiology, Tokyo Medical and Dental University, Tokyo (Japan); Saito, Tsutomu [Department of Radiation Oncology, Nihon University Itabashi Hospital, Tokyo (Japan); Onishi, Hiroshi [Department of Radiology, Yamanashi University, Yamanashi (Japan); Karasawa, Katsuyuki [Department of Radiation Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo (Japan); Nemoto, Kenji [Department of Radiation Oncology, Yamagata University, Yamagata (Japan); Nishimura, Yasumasa [Department of Radiation Oncology, Kinki University School of Medicine, Osaka (Japan)

2012-06-01

Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m{sup 2} intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

Conformal radiotherapy for locally advanced juvenile nasopharyngeal angio-fibroma

Directory of Open Access Journals (Sweden)

Supriya Mallick

2015-01-01

Full Text Available Purpose: To assess the efficacy of radiation in the treatment of juvenile nasopharyngeal angiofibroma (JNA. Materials and Methods: Data were retrieved for JNA treated with radiotherapy from 1987-2012. The demographics, treatment and outcome data were recorded in predesigned proforma. Results: Data of 32 patients were retrieved. Median age was 17 years (range: 12-33 years. All patients received radiation because of refractory, residual or unresectable locally advanced disease. All patients were planned with a three-dimensional conformal technique (3DCRT. The median radiation dose was 30 Gray (range: 30-45 Gray. Median follow-up was 129 months (range: 1-276 months. At the last follow-up, 13 patients were found to have a radiological complete response. Two patients progressed 38 and 43 months after completion of treatment and opted for alternative treatment. One patient developed squamous cell carcinoma of the nasal ale 15 years after radiation. Conclusion: Conformal radiotherapy shows promise as an alternative treatment approach for locally advanced JNA and confers long-term disease control with minimal toxicity.

Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

International Nuclear Information System (INIS)

Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Tao, May Lin; Goodman, Karyn A.; Keating, Nancy L.

2009-01-01

Purpose: To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally advanced, unresectable non-small-cell lung cancer (NSCLC). Methods and Materials: We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists' treatment recommendations for three scenarios with the least agreement. Results: Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55 year old. However, there was substantial variability in recommendations for a 55 year old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p < 0.05), but the impact was modest. Conclusions: Nearly all radiation oncologists report following the evidence-based recommendation of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC, but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly affected treatment recommendations. Additional clinical trial data are necessary to guide recommendations for treatment of elderly patients and patients with poor pulmonary function to optimize their management.

Predictors of severe late radiotherapy-related toxicity after hyperfractionated radiotherapy with or without concomitant cisplatin in locally advanced head and neck cancer. Secondary retrospective analysis of a randomized phase III trial (SAKK 10/94)

International Nuclear Information System (INIS)

Ghadjar, Pirus; Simcock, Mathew; Zimmermann, Frank; Betz, Michael; Bodis, Stephan; Bernier, Jacques; Studer, Gabriela; Aebersold, Daniel M.

2012-01-01

Background and purpose: This secondary analysis was performed to identify predictive factors for severe late radiotherapy (RT)-related toxicity after treatment with hyperfractionated RT +/− concomitant cisplatin in locally advanced head and neck cancer. Materials and methods: Patients were retrospectively analyzed from the previously reported randomized phase III trial: SAKK 10/94. Severe late RT-related toxicity was defined as late RTOG ⩾ grade 3 toxicity starting 3 months after end of RT and/or potential treatment-related death within 3 years of randomization. Results: Two hundred and thirteen randomized patients were analyzed; 84 (39%) experienced severe late RT-related toxicity. With median follow-up of 9.7 years (range, 0.4–15.4 years), median time to severe late RT-related toxicity was 9.6 years. In the univariate Cox proportional hazards model the following variables were associated with severe late RT-related toxicity: advanced N-classification (p < 0.001); technically unresectable disease (p = 0.04); weight loss ratio (p = 0.003); supportive measures (p = 0.009) and severe acute dysphagia (p = 0.001). In the subsequent multivariate analysis all variables except use of supportive measures remained statistically significant. Conclusions: Chemotherapy did not appear to affect severe late RT-related toxicity, but advanced N-classification, technically unresectable disease, weight loss ratio, and severe acute dysphagia were independent predictive factors for severe late RT-related toxicity.

Phase I clinical study of concurrent chemoradiation with hydroxycamptothecine for unresectable or locally relapsed rectal cancer

International Nuclear Information System (INIS)

Li Ning; Jin Jing; Li Yexiong

2012-01-01

Objective: To determine the maximal tolerated dose and the dose-limiting toxicity of hydroxycamptothecine (HCPT) concurrently combined with three-dimensional conformal radiotherapy (3DCRT) for unresectable or locally relapsed rectal cancer. Methods: Twenty-two patients with rectal cancer were enrolled into phase I study between 2004 -2007. HCPT was intravenously administered concurrently with 3DCRT weekly, dose given from 6, 8, 10 mg/m 2 or twice a week, dose given from 4, 6, 8, 10 mg/m 2 , respectively. Total radiation dose of 50 Gy was delivered to the whole pelvis at a fraction of 2 Gy per day for 5 weeks, with 10 - 16 Gy subsequent boost to tumor area. Dose-limiting toxicities (DLT) were defined as grade 3 or higher non-hematologic toxicity or grade 4 hematologic toxicity. Results: In the twice a week group, DLTs of grade 3 diarrhea were observed in 2 patient treated at dose of 6 mg/m 2 . In the weekly group, DLTs of grade 3 diarrhea and radiation-induced dermatitis were observed in I patient at dose of 8 mg/m 2 , and were not observed in the next 3 patients at the same dose level. However, at dose of 10 mg/m 2 , 2 patients had grade 3 diarrhea or nausea. The 5-year overall survival rate was 23% and the median survival time was 18 months. Conclusions: HCPT given concurrently with 3DCRT is safe and tolerable for patients with unresectable or locally relapsed rectal cancer. Either 8 mg/m 2 weekly or 4 mg/m 2 twice a week can be recommended for further study. The dose-limiting toxicities are grade 3 diarrhea, nausea and radiation-induced dermatitis. (authors)

A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas

Energy Technology Data Exchange (ETDEWEB)

Thompson, Reid F.; Zhai, Huifang; Both, Stefan; Metz, James M.; Plastaras, John P.; Ben-Josef, Edgar, E-mail: Edgar.Ben-Josef@uphs.upenn.edu [University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Mayekar, Sonal U. [Thomas Jefferson University, Philadelphia, Pennsylvania 19107 (United States); Apisarnthanarax, Smith [University of Washington, Seattle, Washington 98109 (United States)

2014-08-15

Purpose: Uncontrolled local growth is the cause of death in ∼30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. Methods: The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Results: Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6–53.8 and 34.9–52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Conclusions: Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Robertson, John M., E-mail: jrobertson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Margolis, Jeffrey [Division of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Jury, Robert P. [Department of Surgery, William Beaumont Hospital, Royal Oak, MI (United States); Balaraman, Savitha; Cotant, Matthew B.; Ballouz, Samer; Boxwala, Iqbal G.; Jaiyesimi, Ishmael A.; Nadeau, Laura [Division of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Hardy-Carlson, Maria [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, TX (United States); Marvin, Kimberly S.; Wallace, Michelle; Ye Hong [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

2012-02-01

Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m{sup 2}) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

International Nuclear Information System (INIS)

Robertson, John M.; Margolis, Jeffrey; Jury, Robert P.; Balaraman, Savitha; Cotant, Matthew B.; Ballouz, Samer; Boxwala, Iqbal G.; Jaiyesimi, Ishmael A.; Nadeau, Laura; Hardy-Carlson, Maria; Marvin, Kimberly S.; Wallace, Michelle; Ye Hong

2012-01-01

Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0–2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m 2 ) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma

International Nuclear Information System (INIS)

Franzius, Ch.; Eckardt, J.; Sciuk, J.; Schober, O.; Bielack, S.; Flege, S.; Juergens, H.

2001-01-01

Purpose: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Patients and Methods: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. Results: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors. (orig.)

Targeting chemotherapy via arterial infusion for advanced gastric cancer

Directory of Open Access Journals (Sweden)

Zhi-yu CAO

2011-10-01

Full Text Available Objective To evaluate the clinical effects of chemotherapy via arterial infusion in treatment of advanced gastric cancer.Methods Forty-seven patients with advanced gastric cancer were given chemotherapy via arterial infusion.Chemotherapy plan was as follows: 5-Fluorouracil(Fu 500mg/m2,cyclophosphamide(MMX 10mg/m2,Hydroxycamptothecin(HPT 20mg/m2,once per week,2 weeks as a course,a total of 2-3 courses.Results After chemotherapy via arterial infusion,complete remission(CR was achieved in 1 case,partial remission(PR in 28 cases,stabilization of disease(SD in 16 cases,progression of disease(PD was found in 2 cases,and rate with response(CR+PR was 61.7%.Four of 28 PR patients underwent tumorectomy,the pathology revealed the presence of cancer cells around the vascular vessels,manifesting karyopyknosis,karyorrhexis,coagulation and necrosis of cytoplasm,intercellular edema,hyperplasia of fibroblasts,inflammatory cell infiltration,thickening of endothelium,and thrombosis.One,two and three-year survival rates were 70.2%,14.9% and 2.1%,respectively.The average survival period was 17.2 months.Conclusion Targeting chemotherapy via arterial infusion,as a part of the combined treatment,is beneficial to the patients with unresectable advanced gastric cancer.

Use of Yttrium-90 glass microspheres (TheraSphere) for the treatment of unresectable hepatocellular carcinoma in patients with portal vein thrombosis.

Science.gov (United States)

Salem, Riad; Lewandowski, Robert; Roberts, Carol; Goin, James; Thurston, Kenneth; Abouljoud, Marwan; Courtney, Angi

2004-04-01

Intra-arterial injection of Yttrium-90 glass microspheres ((90)Y- microS; TheraSphere, MDS Nordion, Ottawa, Canada) is indicated for treatment of unresectable hepatocellular carcinoma (HCC) in the presence of acceptable liver function. This study presents hepatic toxicity results after unilobar and bilobar intra-arterial administration of (90)Y- microS in patients with unresectable HCC who had known portal vein thrombosis (PVT) without evidence of cavernous transformation. Fifteen patients with unresectable HCC and PVT of one or both first order and related segmental portal venous branches received a total of 29 infusions of (90)Y- microS for treatment of HCC. All patients had pretreatment evaluation including: computed tomography (CT) imaging, alpha-fetoprotein (AFP) levels, liver function tests, technetium-99m macroaggregated albumin ((99)Tc-MAA) scan for evaluation of lung and visceral shunting, and angiography with visualization into the portal venous phase. (90)Y- micro S dose was based on lobar hepatic volume with adjustment for lung shunt activity. Liver toxicity was assessed by serum total bilirubin graded for severity according to the NIH NCI Clinical Toxicity Criteria (CTC version 2.0). Other adverse events were reported according to the standards established by the Society of Interventional Radiology. There were no procedural complications with delivery of (90)Y- microS, and treatment was well tolerated by all patients. Increased post-treatment bilirubin levels were observed across all treatments in five patients, four of whom had CT or AFP evidence of intrahepatic disease progression. After initial treatment, two patients developed bilirubin toxicity (grades 1 and 2); one patient demonstrated an increment in bilirubin toxicity grade (grade 1 to grade 3) and one patient had an improvement in grade after initial treatment. There were no new treatment-related toxicities in nine patients after a second treatment. (90)Y- microS treatment was well tolerated

Pre-T Cell Receptors (Pre-TCRs) Leverage Vβ Complementarity Determining Regions (CDRs) and Hydrophobic Patch in Mechanosensing Thymic Self-ligands.

Science.gov (United States)

Das, Dibyendu Kumar; Mallis, Robert J; Duke-Cohan, Jonathan S; Hussey, Rebecca E; Tetteh, Paul W; Hilton, Mark; Wagner, Gerhard; Lang, Matthew J; Reinherz, Ellis L

2016-12-02

The pre-T cell receptor (pre-TCR) is a pTα-β heterodimer functioning in early αβ T cell development. Although once thought to be ligand-autonomous, recent studies show that pre-TCRs participate in thymic repertoire formation through recognition of peptides bound to major histocompatibility molecules (pMHC). Using optical tweezers, we probe pre-TCR bonding with pMHC at the single molecule level. Like the αβTCR, the pre-TCR is a mechanosensor undergoing force-based structural transitions that dynamically enhance bond lifetimes and exploiting allosteric control regulated via the Cβ FG loop region. The pre-TCR structural transitions exhibit greater reversibility than TCRαβ and ordered force-bond lifetime curves. Higher piconewton force requires binding through both complementarity determining region loops and hydrophobic Vβ patch apposition. This patch functions in the pre-TCR as a surrogate Vα domain, fostering ligand promiscuity to favor development of β chains with self-reactivity but is occluded by α subunit replacement of pTα upon αβTCR formation. At the double negative 3 thymocyte stage where the pre-TCR is first expressed, pre-TCR interaction with self-pMHC ligands imparts growth and survival advantages as revealed in thymic stromal cultures, imprinting fundamental self-reactivity in the T cell repertoire. Collectively, our data imply the existence of sequential mechanosensor αβTCR repertoire tuning via the pre-TCR. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Shinoto, Makoto, E-mail: shinoto@saga-himat.jp [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu (Japan); Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yamada, Shigeru [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Terashima, Kotaro [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yasuda, Shigeo [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Shioyama, Yoshiyuki [Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Kamada, Tadashi; Tsujii, Hirohiko [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Saisho, Hiromitsu [Department of Internal Medicine and Clinical Oncology, Kaken Hospital, Chemotherapy Research Institute, Chiba (Japan); Asano, Takehide; Yamaguchi, Taketo; Amano, Hodaka; Ishihara, Takeshi; Otsuka, Masayuki; Matsuda, Masamichi; Kainuma, Osamu; Funakoshi, Akihiro; Furuse, Junji; Nakagori, Toshio; Okusaka, Takuji; and others

2016-05-01

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.

Novel approaches of chemoradiotherapy in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

Science.gov (United States)

Stinchcombe, Thomas E; Bogart, Jeffrey A

2012-01-01

Approximately one third of patients with non-small cell lung cancer have unresectable stage IIIA or stage IIIB disease, and appropriate patients are candidates for chemoradiotherapy with curative intent. The optimal treatment paradigm is currently undefined. Concurrent chemoradiotherapy, compared with sequential chemotherapy and thoracic radiation therapy (TRT), results in superior overall survival outcomes as a result of better locoregional control. Recent trials have revealed efficacy for newer chemotherapy combinations similar to that of older chemotherapy combinations with concurrent TRT and a lower rate of some toxicities. Ongoing phase III trials will determine the roles of cisplatin and pemetrexed concurrent with TRT in patients with nonsquamous histology, cetuximab, and the L-BLP25 vaccine. It is unlikely that bevacizumab will have a role in stage III disease because of its toxicity. Erlotinib, gefitinib, and crizotinib have not been evaluated in stage III patients selected based on molecular characteristics. The preliminary results of a phase III trial that compared conventionally fractionated standard-dose TRT (60 Gy) with high-dose TRT (74 Gy) revealed an inferior survival outcome among patients assigned to the high-dose arm. Hyperfractionation was investigated previously with promising results, but adoption has been limited because of logistical considerations. More recent trials have investigated hypofractionated TRT in chemoradiotherapy. Advances in tumor targeting and radiation treatment planning have made this approach more feasible and reduced the risk for normal tissue toxicity. Adaptive radiotherapy uses changes in tumor volume to adjust the TRT treatment plan during therapy, and trials using this strategy are ongoing. Ongoing trials with proton therapy will provide initial efficacy and safety data.

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

International Nuclear Information System (INIS)

Ben-Josef, Edgar; Schipper, Mathew; Francis, Isaac R.; Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel; Simeone, Diane M.; Sonnenday, Christopher; Abrams, Ross; Leslie, William; Khan, Gazala; Zalupski, Mark M.

2012-01-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥1500/mm 3 , platelets ≥100,000/mm 3 , creatinine 2 /100 min intravenously) was given on days −22 and −15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) ≥3, neutropenic fever, or deterioration in performance status to ≥3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.

Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities.

Science.gov (United States)

Goin, James E; Salem, Riad; Carr, Brian I; Dancey, Janet E; Soulen, Michael C; Geschwind, Jean Francois H; Goin, Kathleen; Van Buskirk, Mark; Thurston, Kenneth

2005-02-01

Intraarterial injection of yttrium 90 microspheres (TheraSpheres) is used in the treatment of hepatocellular carcinoma (HCC). This article presents an analysis of the incidence of liver toxicities (liver-related events) and pretreatment factors associated with liver toxicities after TheraSphere treatment. Eighty-eight TheraSphere-treated patients with low 90-day mortality risk were selected for analysis, with liver toxicities coded with use of standard oncology criteria. Descriptive and inferential statistical methods were applied to estimate the incidence of liver toxicities and to evaluate the influence of liver radiation dose and various pretreatment factors on the risk of their occurrence. Sixty-eight liver toxicities occurred in 37 of the 88 patients (42%). Thirty-two patients (36%) experienced 50 liver toxicities after the first treatment and nine of 23 patients (39%) who received a second treatment experienced 18 liver toxicities. Pretreatment total bilirubin and liver radiation dose were found to be associated with the risk of at least one liver toxicity and with the time to first occurrence of a liver toxicity after first treatment. Pretreatment total bilirubin also was associated with liver toxicities after the second treatment. Most of the toxicities resolved; however, those that did not resolve were attributed to tumor progression or advancing cirrhosis. The risk of liver toxicities in patients with unresectable HCC treated with TheraSpheres increases with increasing pretreatment total bilirubin level and liver radiation dose to a maximum of 150 Gy for a single administration. The toxicities attributed to treatment resolved over time, and none of the patients studied had confirmed radiation-induced liver disease. Consequently, doses as high as 150 Gy on a single administration and as high as 268 Gy on repeated administrations were well tolerated.

Personalized medicine for non-small-cell lung cancer: implications of recent advances in tissue acquisition for molecular and histologic testing.

Science.gov (United States)

Moreira, Andre L; Thornton, Raymond H

2012-09-01

In light of recent advances in individualized therapy for non-small-cell lung cancer (NSCLC), molecular and histologic profiling is essential for guiding therapeutic decisions. Results of these analyses may have implications for both response (eg, molecular testing for EGFR [epidermal growth factor receptor] mutations) and safety (eg, contraindications for squamous histology) in NSCLC. Most patients with NSCLC present with unresectable advanced disease; therefore, greater emphasis is being placed on minimally invasive tissue acquisition techniques, such as small biopsy and cytology specimens. Due to the need for increasing histologic and molecular information and increasingly smaller tissue sample sizes, efforts must be focused on optimizing tissue acquisition and the development of more sensitive molecular assays. Recent advances in tissue acquisition techniques and specimen preservation may help to address this challenge and lead to enhanced personalized treatment in NSCLC. Copyright © 2012 Elsevier Inc. All rights reserved.

French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

International Nuclear Information System (INIS)

Bensadoun, Rene-Jean; Benezery, Karen; Dassonville, Olivier; Magne, Nicolas; Poissonnet, Gilles; Ramaioli, Alain; Lemanski, Claire; Bourdin, Sylvain; Tortochaux, Jacques; Peyrade, Frederic; Marcy, Pierre-Yves; Chamorey, Emmanuel Phar; Vallicioni, Jacques; Seng Hang; Alzieu, Claude; Gery, Bernard; Chauvel, Pierre; Schneider, Maurice; Santini, Jose; Demard, Francois; Calais, Gilles

2006-01-01

Background: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Methods: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1 → D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m 2 (D1, D22, D43); 5FU, continuous infusion (D1 → D5), 750 mg/m 2 /day cycle 1; 430 mg/m 2 /day cycles 2 and 3. Results: A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. Conclusion: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an 'aggressive' dose-intensity radiotherapy schedule

Safety and Efficacy of Radiofrequency Ablation in the Management of Unresectable Bile Duct and Pancreatic Cancer: A Novel Palliation Technique

Directory of Open Access Journals (Sweden)

Paola Figueroa-Barojas

2013-01-01

Full Text Available Objectives. Radiofrequency ablation (RFA has replaced photodynamic therapy for premalignant and malignant lesions of the esophagus. However, there is limited experience in the bile duct. The objective of this pilot study was to assess the safety and efficacy of RFA in malignant biliary strictures. Methods: Twenty patients with unresectable malignant biliary strictures underwent RFA with stenting between June 2010 and July 2012. Diameters of the stricture before and after RFA, immediate and 30 day complications and stent patency were recorded prospectively. Results. A total of 25 strictures were treated. Mean stricture length treated was 15.2 mm (SD = 8.7 mm, Range = 3.5–33 mm. Mean stricture diameter before RFA was 1.7 mm (SD = 0.9 mm, Range = 0.5–3.4 mm while the mean diameter after RFA was 5.2 mm (SD = 2 mm, Range = 2.6–9 mm. There was a significant increase of 3.5 mm (t = 10.8, DF = 24, P value = <.0001 in the bile duct diameter post RFA. Five patients presented with pain after the procedure, but only one developed mild post-ERCP pancreatitis and cholecystitis. Conclusions: Radiofrequency ablation can be a safe palliation option for unresectable malignant biliary strictures. A multicenter randomized controlled trial is required to confirm the long term benefits of RFA and stenting compared to stenting alone.

Feasibility of accelerated radiotherapy (AR) using a concomitant boost for the treatment of unresectable non-small cell lung cancer (NSCLC): a phase II study

International Nuclear Information System (INIS)

Kumar, Parvesh; Wan, Jim; Paig, Camilo U.; Kun, Larry E.; Niell, H. Barry

1996-01-01

Purpose/Objective: The feasibility of AR using a concomitant boost in the treatment of unresectable NSCLC was prospectively tested in a phase II study. Materials and Methods: Twenty patients were enrolled to the protocol between 11/90 and 5/93. Stage distribution was as follows: Medically inoperable stage I = 5 (T 1 = 1, T 2 = 4), stage IIIA = 1, and stage IIIA(N 2 ) = 14. Planned AR delivered a total dose of 65 Gy in 45 fractions over five weeks using a 'field within a field technique'. The large field (day 1, a.m.) encompassed the primary lesion and adjacent lymph nodes to 45 Gy at 1.8 Gy/fraction (fx). A CT planned small field (day 8, >6 hours apart in p.m.) included only the primary lesion and overt nodal disease to 20 Gy at 1.0 Gy/fx. Doses were not corrected for lung inhomogeneity. Results: Median age of the 20 male enrolled patients was 68 years (range = 42-80 years). Eighteen (90%) of 20 patients completed the planned AR without any interruptions in therapy. One patient experienced a 4 day interruption due to tumor related obstructive pneumonia while the other patient missed 2 days secondary to non-treatment related small bowel obstruction. No incidence of grade ≥3 esophagitis was observed. One patient experienced pneumonitis within the radiation portal 1 month post-RT which response d to corticosteroid therapy; otherwise, no late sequelae were observed. The median total delivered dose was 65 Gy (range 64.0-65.4). At a minimum follow-up interval of 30 months, the 2-year Kaplan-Meier and median survival are 15% and 13.4 months, respectively for all 20 patients. Conclusion: AR using a concomitant boost to 65 Gy in 5 weeks for unresectable NSCLC is feasible with minimal acute or long term toxicity. Median survival in our study was similar to the chemo radiation arms of CALGB 8433 and RTOG 8808 protocols. Protocols which combine AR with chemotherapy should be explored for unresectable NSCLC

Epithelial cells prime the immune response to an array of gut-derived commensals towards a tolerogenic phenotype through distinct actions of thymic stromal lymphopoietin and transforming growth factor-beta

DEFF Research Database (Denmark)

Zeuthen, Louise Hjerrild; Fink, Lisbeth Nielsen; Frøkiær, Hanne

2007-01-01

in DC priming of naive T cells with elevated levels of transforming growth factor-beta (TGF-beta) and markedly reduced levels of bacteria-induced interferon-gamma production. Caco2 cell production of IL-8, thymic stromal lymphopoietin (TSLP) and TGF-beta increases upon microbial stimulation in a strain...

Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer

International Nuclear Information System (INIS)

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito

2014-01-01

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10–12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7–40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted. (author)

Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era?

Science.gov (United States)

Mocellin, Simone; Pilati, Pierluigi; Lise, Mario; Nitti, Donato

2007-12-10

The treatment of unresectable liver-confined metastatic disease from colorectal cancer (CRC) is a challenging issue. Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomized controlled trials (RCT) comparing HAI with systemic chemotherapy (SCT). To date, 10 RCTs have been published, for a total of 1,277 patients enrolled. For tumor response rates, relative risks (RR) and their 95% CIs were obtained from raw data; for OS, hazard ratios (HRs) and their 95% CIs were extrapolated from the Kaplan-Meier survival curves. HAI regimens were based on floxuridine (FUDR) in nine of 10 RCTs, whereas in one RCT, fluorouracil (FU) + leucovorin was used. SCT consisted of FUDR, FU, FU + leucovorin, or a miscellany of FU and best supportive care in three, one, four, and two studies, respectively. Pooling the data, tumor response rate was 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < .0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively; the meta-risk of death was not statistically different between the two study groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = .24). Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases, at least as a first-line therapy.

Experience in colon sparing surgery in North America: advanced endoscopic approaches for complex colorectal lesions.

Science.gov (United States)

Gorgun, Emre; Benlice, Cigdem; Abbas, Maher A; Steele, Scott

2018-07-01

Need for colon sparing interventions for premalignant lesions not amenable to conventional endoscopic excision has stimulated interest in advanced endoscopic approaches. The aim of this study was to report a single institution's experience with these techniques. A retrospective review was conducted of a prospectively collected database of all patients referred between 2011 and 2015 for colorectal resection of benign appearing deemed endoscopically unresectable by conventional endoscopic techniques. Patients were counseled for endoscopic submucosal dissection (ESD) with possible combined endoscopic-laparoscopic surgery (CELS) or alternatively colorectal resection if unable to resect endoscopically or suspicion for cancer. Lesion characteristic, resection rate, complications, and outcomes were evaluated. 110 patients were analyzed [mean age 64 years, female gender 55 (50%), median body mass index 29.4 kg/m 2 ]. Indications for interventions were large polyp median endoscopic size 3 cm (range 1.5-6.5) and/or difficult location [cecum (34.9%), ascending colon (22.7%), transverse colon (14.5%), hepatic flexure (11.8%), descending colon (6.3%), sigmoid colon (3.6%), rectum (3.6%), and splenic flexure (2.6%)]. Lesion morphology was sessile (N = 98, 93%) and pedunculated (N = 12, 7%). Successful endoscopic resection rate was 88.2% (N = 97): ESD in 69 patients and CELS in 28 patients. Complication rate was 11.8% (13/110) [delayed bleeding (N = 4), perforation (N = 3), organ-space surgical site infection (SSI) (N = 2), superficial SSI (N = 1), and postoperative ileus (N = 3)]. Out of 110 patients, 13 patients (11.8%) required colectomy for technical failure (7 patients) or carcinoma (6 patients). During a median follow-up of 16 months (range 6-41 months), 2 patients had adenoma recurrence. Advanced endoscopic surgery appears to be a safe and effective alternative to colectomy for patients with complex premalignant lesions deemed

Preoperative Transcatheter Selective Arterial Chemoembolization in Treatment of Unresectable Hepatoblastoma in Infants and Children

International Nuclear Information System (INIS)

Li Jiaping; Chu Jianping; Yang Jianyong; Chen Wei; Wang Yu; Huang Yonghui

2008-01-01

The purpose of this study was to evaluate the clinical feasibility and efficacy of transcatheter selective arterial chemoembolization (TACE) for unresectable hepatoblastoma in infants and children. The study was performed with the approval of our institutional review board. Sixteen patients (13 boys, 3 girls) with unresectable hepatoblastoma were treated one to three times with preoperative TACE in an effort to improve the surgical and clinical outcome. Their ages ranged from 50 days to 60 months, with a mean age of 20.4 months. All cases were pathologically proved hepatoblastoma by fine-needle biopsy. After an intra-arterial catheter was selectively inserted into the main feeding artery of the tumor, cycles of cisplatin (40 to 50 mg/m 2 ) and adriamycin (20 to 30 mg/m 2 ) mixed with lipiodol were given, followed by gelatin foam particles or stainless-steel coils. Tumor response was evaluated according to tumor shrinkage, α-fetoprotein (AFP) levels, and pathological findings. TACE procedure was performed one to three times, depending on the patient's response. Surgical resection was carried out when the tumor volume appeared sufficiently reduced to allow safe resection by either lobectomy or extended lobectomy. A marked reduction in tumor size associated with decreased AFP level occurred after treatment. According to paired-samples test, tumor shrinkage ranged from 19.0% to 82.0%, with a mean value of 59.2%. AFP levels decreased 99.0% to 29.0% from initial levels, with a mean decrease of 60.0%. TACE allowed subsequent complete surgical resection in 13 cases and the other 3 cases underwent partial resection. One patient underwent successful orthotopic liver transplantation after receiving TACE therapy. Pathological examination showed that the mean percentage of necrotic area in the surgical specimens was 87%. Overall survival rate at 1, 3, and 5 years was 87.5%, 68.7%, and 50%, respectively. Correspondingly, event-free survival rate was 75%, 62.5%, and 43

Safety and efficacy of enzyme targeting intraoperative radiosensitization therapy (KORTUC-IORT) for advanced pancreatic cancer

International Nuclear Information System (INIS)

Nishioka, Akihito; Hamada, Norihiko; Kariya, Shinji; Ogawa, Yasuhiro

2012-01-01

We developed a new radiosensitizer injection containing hydrogen peroxide and sodium hyaluronate just followed by intraoperative radiotherapy (IORT) for locally advanced pancreatic cancer, named KORTUC-IORT (Kochi Oxydol-Radiation Therapy for Unresectable Carcinoma + IORT). Fourteen patients were treated with KORTUC-IORT, external beam radiotherapy (EBRT), and systemic chemotherapy. With KORTUC-IORT, the agent containing hydrogen peroxide and sodium hyaluronate, was injected into tumor tissue just prior to administration of IORT under ultrasonic guidance. All treatments related with KORTUC-IORT were well tolerated, with few adverse effects. One year survival rate is 67% and median survival period is 15 months. The present formulation can be delivered safely and effectively under the conditions used. (author)

A human thymic epithelial cell culture system for the promotion of lymphopoiesis from hematopoietic stem cells.

Science.gov (United States)

Beaudette-Zlatanova, Britte C; Knight, Katherine L; Zhang, Shubin; Stiff, Patrick J; Zúñiga-Pflücker, Juan Carlos; Le, Phong T

2011-05-01

A human thymic epithelial cell (TEC) line expressing human leukocyte antigen-ABC and human leukocyte antigen-DR was engineered to overexpress murine Delta-like 1 (TEC-Dl1) for the purpose of establishing a human culture system that supports T lymphopoiesis from hematopoietic progenitor cells (HPCs). Cord blood or bone marrow HPCs were co-cultured with either the parental TEC line expressing low levels of the Notch ligands, Delta-like 1 and Delta-like 4, or with TEC-Dl1 to determine if these cell lines support human lymphopoiesis. In co-cultures with cord blood or bone marrow HPCs, TEC-Dl1 cells promote de novo generation of CD7(pos)CD1a(pos) T-lineage committed cells. Most CD7(pos)CD1a(hi) cells are CD4(pos)CD8(pos) double-positive (DP). We found that TEC-Dl1 cells are insufficient to generate mature CD3(hi) CD4(pos) or CD3(hi) CD8(pos) single-positive (SP) T cells from the CD4(pos)CD8(pos) DP T cells; however, we detected CD3(lo) cells within the DP and SP CD4 and CD8 populations. The CD3(lo) SP cells expressed lower levels of interleukin-2Rα and interleukin-7Rα compared to CD3(lo) DP cells. In contrast to the TEC-Dl1 line, the parental TEC-84 line expressing low levels of human Notch ligands permits HPC differentiation to the B-cell lineage. We report for the first time a human TEC line that supports lymphopoiesis from cord blood and bone marrow HPC. The TEC cell lines described herein provide a novel human thymic stroma model to study the contribution of human leukocyte antigen molecules and Notch ligands to T-cell commitment and maturation and could be utilized to promote lymphopoiesis for immune cell therapy. Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Correlation between the CT manifestations and post-operative survival time in patients with thymic epithelial tumor

International Nuclear Information System (INIS)

Chen Juan; Tan Ye; Wang Xiangyang; Du Jun; Pan Jishu; Wei Jiahu

2011-01-01

Objective: To describe the CT manifestations of thymic epithelial tumor and explore the correlation between CT findings and post-operative tumor-related survival time. Methods: Ninety-one patients who underwent CT scan before operation were reviewed retrospectively. All cases had operation and were classified according to the WHO classification. The size, contour, shape, density and enhancement of the tumors on CT were assessed. Presence of mediastinal lymphadenopathy, great vessel invasion, metastasis to the lung or plural, myasthenia gravis (MG) were also analyzed. The survival rate was obtained using, the Kaplan-Meier method. The Cox model was applied to determine the factors affecting the tumor-related survivals. Chi square test was used to analyze the relationship between CT findings and WHO classification. Results: Two patients were excluded because of dying of myocardial infarction and colon cancer. The total 5-year survival rate was 84.3% (n=75). Eighty-nine patients had total 91 tumors. Tumors with diameter larger than 5 cm, lobular contour, heterogenous density, and presence of great vessel invasion, mediastinal lymphadenopathy, and metastasis were adverse factors which could significantly affect the survival time. Five-year survival rates of these factors were 72.7%, 77.3%, 76.7%, 73.8%, 30.0%, and 68.8%, respectively. Presence of MG was a favorable factor which also significantly affected the survival time (P 0.05). The result of the Cox multivariate analysis was consistent with that of the Log-rank test. For different WHO classification, there were significant different among the size or contour of the tumors, presence of great vessel invasion, mediastinal lymphadenopathy, and metastasis (χ 2 value were 6.598, 5.737, 18.307, 8.465, and 15.608, respectively P<0.05). Conclusions: CT findings may be served as predictors of clinical prognosis of the thymic epithelial tumors. Adverse factors for survival time are the size of the tumors and presence of

Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy.

Science.gov (United States)

Song, Jeong Ah; Park, Hyun-Ju; Yang, Mi-Jin; Jung, Kyung Jin; Yang, Hyo-Seon; Song, Chang-Woo; Lee, Kyuhong

2014-07-01

Polyhexamethyleneguanidine phosphate (PHMG-P) has been widely used as a disinfectant because of its strong bactericidal activity and low toxicity. However, in 2011, the Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare reported that a suspicious outbreak of pulmonary disease might have originated from humidifier disinfectants. The purpose of this study was to assess the toxicity of PHMG-P following direct exposure to the lung. PHMG-P (0.3, 0.9, or 1.5 mg/kg) was instilled into the lungs of mice. The levels of proinflammatory markers and fibrotic markers were quantified in lung tissues and flow cytometry was used to evaluate T cell distribution in the thymus. Administration of PHMG-P induced proinflammatory cytokines elevation and infiltration of immune cells into the lungs. Histopathological analysis revealed a dose-dependent exacerbation of both inflammation and pulmonary fibrosis on day 14. PHMG-P also decreased the total cell number and the CD4(+)/CD8(+) cell ratio in the thymus, with the histopathological examination indicating severe reduction of cortex and medulla. The mRNA levels of biomarkers associated with T cell development also decreased markedly. These findings suggest that exposure of lung tissue to PHMG-P leads to pulmonary inflammation and fibrosis as well as thymic atrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preoperative CT prediction for Masaoka staging of thymic epithelial tumor

International Nuclear Information System (INIS)

Feng Zhan; Huang Zhen; Zhang Liang

2013-01-01

Objective: To discuss the value of CT prognosis on the Masaoka staging system of thymic epithelial tumors (TET) before surgical resection. Methods: The CT images of 102 patients with TET proved by surgery and pathology were reviewed retrospectively. The TET were reclassified according to Masaoka stage system. The size, homogeneity, sharp, contour, infiltration of surrounding tissue, and metastasis on CT were analyzed with Logistic analysis. The diagnostic value was also evaluated with a ROC curve. Results: Masaoka pathologic stages were stage Ⅰ for 36 (35.3 %), stage Ⅱ for 27 (26.5 %), stage Ⅲ for 30 (29.4 %), and stage Ⅳ for 9 (8.8 %). A multivariable Logistic regression model showed that TET with larger size of tumor (20/35, P = 0.0371, OR = 4.539), irregular or lobulated tumor contour (26/42, P = 0.0230, OR = 4.870), heterogeneous (21/33, P = 0.0154, OR = 6.020), infiltration of surrounding fat (25/32, P = 0.0019, OR = 14.005), and pleural seeding (11/11, P = 0.0032, OR = 36.153) were more likely to have stage Ⅲ or Ⅳ disease. The area under ROC curve was 0.940. Conclusions: The tumor CT imaging features can differentiate between stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ disease. This helps identified patients more likely to benefit from neoadjuvant therapy. (authors)

Apparent failure of thymic epithelium transplants to alter the course of autoimmune disease in NZB/W mice

International Nuclear Information System (INIS)

Morrow, W.J.W.; Nayak, R.C.; Cooke, A.; Roitt, I.M.

1982-01-01

Thymic epithelium from neonatal DBA/2 mice (H-2sup(d)) was placed under the kidney capsule of 10- to 12-wk-old female NZB/W mice (H-2sup(d/z)). Donor epithelium, equivalent to 1-2 lobes of neonatal thymus, was either irradiated (1300 rad.) or cultured for 7 days in order to minimise host-versus-graft reactions. Histological examination showed that the epithelium repopulated and remained in place until the end of the experiment, with no sign of rejection. Despite this, the treated animals lived no longer than the untreated or sham operated controls. Levels of anti-nuclear antibody and serum IgM (normally highly elevated in these animals) were not significantly different in any group. (Auth.)

Is Stereotactic Body Radiation Therapy an Attractive Option for Unresectable Liver Metastases? A Preliminary Report From a Phase 2 Trial

Energy Technology Data Exchange (ETDEWEB)

Scorsetti, Marta; Arcangeli, Stefano; Tozzi, Angelo; Comito, Tiziana [Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano (Italy); Alongi, Filippo, E-mail: filippo.alongi@humanitas.it [Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano (Italy); Navarria, Pierina; Mancosu, Pietro; Reggiori, Giacomo [Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano (Italy); Fogliata, Antonella [Medical Physics Unit, Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Torzilli, Guido [Surgery Department, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano (Italy); Tomatis, Stefano [Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano (Italy); Cozzi, Luca [Medical Physics Unit, Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)

2013-06-01

Purpose: To evaluate the feasibility of high-dose stereotactic body radiation therapy (SBRT) in the treatment of unresectable liver metastases. Methods and Materials: Patients with 1 to 3 liver metastases, with maximum individual tumor diameters less than 6 cm and a Karnofsky Performance Status of at least 70, were enrolled and treated by SBRT on a phase 2 clinical trial. Dose prescription was 75 Gy on 3 consecutive days. SBRT was delivered using the volumetric modulated arc therapy by RapidArc (Varian, Palo Alto, CA) technique. The primary end-point was in-field local control. Secondary end-points were toxicity and survival. Results: Between February 2010 and September 2011, a total of 61 patients with 76 lesions were treated. Among the patients, 21 (34.3%) had stable extrahepatic disease at study entry. The most frequent primary sites were colorectal (45.9%) and breast (18%). Of the patients, 78.7% had 1 lesion, 18.0% had 2 lesions, and 3.3% had 3 lesions. After a median of 12 months (range, 2-26 months), the in-field local response rate was 94%. The median overall survival rate was 19 months, and actuarial survival at 12 months was 83.5%. None of the patients experienced grade 3 or higher acute toxicity. No radiation-induced liver disease was detected. One patient experienced G3 late toxicity at 6 months, resulting from chest wall pain. Conclusions: SBRT for unresectable liver metastases can be considered an effective, safe, and noninvasive therapeutic option, with excellent rates of local control and a low treatment-related toxicity.

Definitive radiotherapy for locally advanced squamous cell carcinoma of the vulva and technical issues: a case report

International Nuclear Information System (INIS)

Kumar, Gokula; Norhafizah, I; Shazril, I; Nursyatina, AR; Abdul Aziz, MZ; Zin, Hafiz M; Zakir, MK; Norjayadi; Norliza, AS; Khairun, N; Ismail, A

2017-01-01

This case report describes a complex radical 3D-Conformal Radiotherapy treatment planning, dosimetric issues and outcome of definitive treatment of un-resectable carcinoma of the vulvar in a 42-year old lady. The patient presented with large fungating mass of the vulva which was biopsy confirmed as Keratinizing Squamous Cell Carcinoma. Further staging investigation revealed locally advanced disease (T4), with bilateral inguinal lymph nodes involvement. There is no systemic metastasis or intra-pelvic nodes. The patient was seen by Gynae-Oncology team and the disease was deemed un-resectable without significant morbidity. She was treated to a total dose of 64.8Gy in 36 fractions over 7 weeks with concurrent weekly Cisplatinum in 2 phases. 3D-Conformal radiotherapy technique using the modified segmental boost technique (MSBT, large PA and small AP photon fields with inguinal electron matching) was used. TLD chips were used for in-vivo dose verification in phase 1 and 2 of the treatment. At completion of planned radiotherapy, patient had a complete clinical response, grade 2-3 skin toxicity, grade 2 rectal toxicity, and grade 2 dysuria Vulval Squamous Cell Carcinomas are very radiosensitive tumours and the skills of the treating Radiation Oncologist, Dosimetrists, Physicist, Radiation Therapist and also nurses is of foremost importance is ensuring good clinical outcomes. (paper)

The actin regulator coronin-1A is mutated in a thymic egress deficient mouse strain and in a T?B+NK+ SCID patient

OpenAIRE

Shiow, Lawrence R.; Roadcap, David W.; Paris, Kenneth; Watson, Susan R.; Grigorova, Irina L.; Lebet, Tonya; An, Jinping; Xu, Ying; Jenne, Craig N.; F?ger, Niko; Sorensen, Ricardo U.; Goodnow, Christopher C.; Bear, James E.; Puck, Jennifer M.; Cyster, Jason G.

2008-01-01

Mice carrying the recessive peripheral T cell deficiency (Ptcd) locus have a block in thymic egress but the mechanism responsible is undefined. Here we found that Ptcd T cells have an intrinsic migration defect, impaired lymphoid tissue trafficking and irregularly shaped protrusions. Characterization of the Ptcd locus revealed an E26K point mutation within the actin regulator coronin-1A (Coro1a) that enhanced its inhibition of the actin regulator Arp2/3 and resulted in its mislocalization fro...

Concurrent Chemotherapy and Pulsed High-Intensity Focused Ultrasound Therapy for the Treatment of Unresectable Pancreatic Cancer: Initial Experiences

Energy Technology Data Exchange (ETDEWEB)

Lee, Jae Young; Choi, Byung Ihn; Ryu, Ji Kon; Kim, Yong Tae; Kim, Se Hyung; Han, Joon Koo [Seoul National University Hospital, Seoul (Korea, Republic of); Hwang, Joo Ha [University of Washington Medical Center, Seattle (United States)

2011-04-15

This study was performed to evaluate the potential clinical value of concurrent chemotherapy and pulsed high intensity focused ultrasound (HIFU) therapy (CCHT), as well as the safety of pulsed HIFU, for the treatment of unresectable pancreatic cancer. Twelve patients were treated with HIFU from October 2008 to May 2010, and three of them underwent CCHT as the main treatment (the CCHT group). The overall survival (OS), the time to tumor progression (TTP), the complications and the current performance status in the CCHT and non-CCHT groups were analyzed. Nine patients in the non-CCHT group were evaluated to determine why CCHT could not be performed more than twice. The OS of the three patients in the CCHT group was 26.0, 21.6 and 10.8 months, respectively, from the time of diagnosis. Two of them were alive at the time of preparing this manuscript with an excellent performance status, and one of them underwent a surgical resection one year after the initiation of CCHT. The TTP of the three patients in the CCHT group was 13.4, 11.5 and 9.9 months, respectively. The median OS and TTP of the non-CCHT group were 10.3 months and 4.4 months, respectively. The main reasons why the nine patients of the non-CCHT group failed to undergo CCHT more than twice were as follows: pancreatitis (n = 1), intolerance of the pain during treatment (n = 4), palliative use of HIFU for pain relief (n = 1) and a poor physical condition due to disease progression (n = 3). No major complications were encountered except one case of pancreatitis. This study shows that CCHT is a potentially effective and safe modality for the treatment of unresectable pancreatic cancer

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a case cohort study.

Science.gov (United States)

Carr, Brian I; Buch, Shama C; Kondragunta, Venkateswarlu; Pancoska, Petr; Branch, Robert A

2008-08-01

A total of 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end-point for all analyses. We found in our overall analysis, that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated alpha-fetoprotein (AFP) or bilirubin or alkaline phosphatases were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient subgroups based on poor liver function and aggressive tumor characteristics. In subgroup analysis based on these subsets, there was clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant, independent but modest risk factors. The results of this large dataset show that amongst nonsurgical HCC patients, there are clear subsets with longer survival than other subsets. This data also supports the concept of heterogeneity of HCC.

Repeated courses of transarterial embolization with polyvinyl alcohol particles: 'long life elixir' in a cirrhotic patient with unresectable hepatocellular carcinoma.

Science.gov (United States)

Marelli, Laura; Shusang, Vibhakorn; Senzolo, Marco; Cholongitas, Evangelos; Goode, Antony; Yu, Dominic; Patch, David W; Burroughs, Andrew K

2007-04-01

Chemoembolization improves survival in selected cirrhotic patients with hepatocellular carcinoma, but prolonged survival is unusual. In this study, a 70-year-old cirrhotic patient, who had a histologically proven hepatocellular carcinoma of 5 cm diameter, embolization with polyvinyl alcohol particles alone, without chemotherapeutic agent, has resulted in continued survival, of 5 years to date, with virtual elimination of residual hypervascularity following 10 sessions of embolization, and with continued patency of the injected branch of the hepatic artery. Provided liver function is maintained, embolization alone appears a feasible long term and effective therapy for unresectable hepatocellular carcinoma.

FOXN1GFP/w Reporter hESCs Enable Identification of Integrin-β4, HLA-DR, and EpCAM as Markers of Human PSC-Derived FOXN1+ Thymic Epithelial Progenitors

Directory of Open Access Journals (Sweden)

Chew-Li Soh

2014-06-01

Full Text Available Thymic epithelial cells (TECs play a critical role in T cell maturation and tolerance induction. The generation of TECs from in vitro differentiation of human pluripotent stem cells (PSCs provides a platform on which to study the mechanisms of this interaction and has implications for immune reconstitution. To facilitate analysis of PSC-derived TECs, we generated hESC reporter lines in which sequences encoding GFP were targeted to FOXN1, a gene required for TEC development. Using this FOXN1GFP/w line as a readout, we developed a reproducible protocol for generating FOXN1-GFP+ thymic endoderm cells. Transcriptional profiling and flow cytometry identified integrin-β4 (ITGB4, CD104 and HLA-DR as markers that could be used in combination with EpCAM to selectively purify FOXN1+ TEC progenitors from differentiating cultures of unmanipulated PSCs. Human FOXN1+ TEC progenitors generated from PSCs facilitate the study of thymus biology and are a valuable resource for future applications in regenerative medicine.

Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

Science.gov (United States)

Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

2017-01-01

Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

Unresectable Retiform Hemangioendothelioma Treated with External Beam Radiation Therapy and Chemotherapy: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Alina Z. Hirsh

2010-01-01

Full Text Available Retiform hemangioendothelioma (RH is an infrequently encountered vascular neoplasm of intermediate or borderline malignancy. Treatment of RH is controversial. We present a case of a 44-year-old Asian male presenting with an unresectable RH of the pelvis. The patient was treated with concurrent low-dose Cisplatin and External beam Radiation (4140cGy in 180cGy per fraction. This is the first report of a clinical complete response and a long-term local control of this rare tumor. This has significant clinical implication, since it gives the first evidence of treatment of this rare tumor using concurrent low-dose chemotherapy and radiation.

Concurrent chemoradiotherapy with nedaplatin and 5-fluorouracil (5-FU) for locally advanced squamous cell carcinoma of the esophagus

International Nuclear Information System (INIS)

Kubo, Naoshi; Morimoto, Junya; Tanaka, Hiroaki

2009-01-01

Concurrent chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is the standard treatment for unresectable locally advanced esophageal carcinoma. Although this regimen has been widely accepted in Japan, the adverse effect of CDDP such as gastrointestinal and renal toxicity may sometimes be the cause of interruption of the treatment, especially among the elderly patients. Cis-diammine-glycolatoplatinum (nedaplatin: CDGP) is a new platinum agent, which was developed with the aim of decreasing renal and gastrointestinal toxicities but maintaining the effectiveness of CDDP. We reported the efficacy and safety of CRT using CDGP and 5-FU for locally advanced squamous cell carcinoma of the esophagus. Between January 2001 and December 2007, 65 patients with locally advanced esophageal cancer (39 patients with unresectable tumor (cT4) and 26 patients with distant lymphnode or bulky lymphnode metastasis) were eligible and given informed consent and cared by the Department of Surgical Oncology of Osaka City University. Patients received a continuous infusion of 5-FU (250 mg/body) on days 1-21. CDGP was administered at the dose of 10 mg/body by bolus infusion for 1 hour on days 1-5, 8-12 and 15-19 just before radiotherapy. Radiotherapy was delivered in 1.8 Gy fractions, 5 days/week for 4 weeks. For the effective cases of CRT, a surgical resection was followed subsequently and an additional radiotherapy at the dose of 20 Gy was performed for non-effective cases. Complete or partial response was achieved in 46 patients (71%). Hematologic toxicities such as grades 3 and 4 leucocytopenia developed in 19 patients and thrombocytopenia developed in 20 patients, which were well tolerated by conservative therapy. Gastrointestinal and renal toxicities were developed in only a few patients. There was no CRT-related death. Of all 65 patients, 25 patients underwent a surgical resection while 19 patients could receive a curative resection (R0 operation). In the resected

Treatment of locally advanced/locally recurrent breast cancer and inflammatory breast cancer

International Nuclear Information System (INIS)

Murakami, Masao

2000-01-01

This paper summarizes the treatment of locally advanced breast cancer, inflammatory breast cancer, and locally recurrent breast cancer. A multidisciplinary approach considering subclinical distant metastases is needed to treat these types of breast cancer. Subclinical distant metastasis is observed in about 80% of case of locally advanced cancer, and treatment of subclinical distant metastases, e.g., by endocrinotherapy and chemotherapy, is therefore essential to improving the prognosis. The standard therapy for unresectable locally advanced breast cancer consists of induction chemotherapy with anthracyclines and local treatment with mastectomy or irradiation. Previous reports have stated that induction chemotherapy was effective in 60-80% of the primary lesions or lymph node metastasis, and the CR rates were in the 10-20% range. Combination therapy with induction chemotherapy clearly improved the outcome over local treatment alone. The usual irradiation dose is 50 to 60 Gy/5 to 7 weeks to the whole breast or the thoracic wall. Boost irradiation at a dose of 10 to 25 Gy is performed in unresectable cases. The boost irradiation dose to the lymph node area is usually 45 to 50 Gy/5 to 6 weeks in cases without gross lesions and 10 to 15 Gy in cases with gross lesions. Combination therapy consisting of conservative pectoral mastectomy and postoperative adjuvant chemo- endocrino-therapy (i.e., adjuvant therapy) has become the standard regimen for treating resectable locally advanced breast cancer, because it significantly improves the recurrence rate and survival rate compared to local treatment alone. Some clinical have studies indicated that neoadjuvant therapy (i.e., induction chemotherapy + surgery/radiation therapy) is comparable or superior to adjuvant therapy in terms of improving the prognosis. However, the efficacy and most appropriate method of breast-conserving therapy after induction chemotherapy are still unclear. More clinical trials are needed. It has been

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Mathew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Simeone, Diane M.; Sonnenday, Christopher [Department of Surgery, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Khan, Gazala; Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States)

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) was given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local

Prognostic and predictive value of liver volume on colorectal cancer patients with unresectable liver metastases

International Nuclear Information System (INIS)

Park, Jun Su; Park, Hee Chul; Choi, Doo Ho; Park, Won; Yu, Jeong Il; Park, Young Suk; Kang, Won Ki; Park, Joon Oh

2014-01-01

To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

Prognostic and predictive value of liver volume on colorectal cancer patients with unresectable liver metastases

Energy Technology Data Exchange (ETDEWEB)

Park, Jun Su; Park, Hee Chul; Choi, Doo Ho; Park, Won; Yu, Jeong Il; Park, Young Suk; Kang, Won Ki; Park, Joon Oh [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2014-06-15

To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

MVP Chemotherapy and Hyperfractionated Radiotherapy for Stage III Unresectable Non-Small Cell Lung Cancer - Randomized for maintenance Chemotherapy vs. Observation; Preliminary Report-

International Nuclear Information System (INIS)

Choi, Euk Kyung; Chang, Hye Sook; Suh, Cheol Won

1991-01-01

To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991. Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGY following 3 cycles of induction MVP (Mitomycin C 6 mg/m 2 , vinblastine 6 mg/m 2 , Cisplatin 60 mg/m 2 ) and randomized for either observation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 16 were analyzed for this preliminary report. The response rate of induction chemotherapy was 62.5%; partial response, 50% and minimal response, 12.5%. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue

Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking

International Nuclear Information System (INIS)

Araki, Tetsuro; Nishino, Mizuki; Hatabu, Hiroto; Gao, Wei; Dupuis, Josee; Hunninghake, Gary M.; Washko, George R.; Murakami, Takamichi; O'Connor, George T.

2016-01-01

To investigate CT appearance and size of the thymus in association with participant characteristics. 2540 supposedly healthy participants (mean age 58.9 years, 51 % female) were evaluated for the CT appearance of thymic glands with four-point scores (according to the ratio of fat and soft tissue), size and morphology. These were correlated with participants' age, sex, BMI and smoking history. Of 2540 participants, 1869 (74 %) showed complete fatty replacement of the thymus (Score 0), 463 (18 %) predominantly fatty attenuation (Score 1), 172 (7 %) half fatty and half soft-tissue attenuation (Score 2) and 36 (1 %) solid thymic gland with predominantly soft-tissue attenuation (Score 3). Female participants showed less fatty degeneration of the thymus with higher thymic scores within age 40-69 years (P < 0.001). Participants with lower thymic scores showed higher BMI (P < 0.001) and were more likely to be former smokers (P < 0.001) with higher pack-years (P = 0.04). Visual assessment with four-point thymic scores revealed a sex difference in the fatty degeneration of the thymus with age. Women show significantly higher thymic scores, suggesting less fat content of the thymus, during age 40-69 years. Cigarette smoking and high BMI are associated with advanced fatty replacement of the thymus. (orig.)

Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking

Energy Technology Data Exchange (ETDEWEB)

Araki, Tetsuro [Harvard Medical School, Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Boston, MA (United States); Kinki University Faculty of Medicine, Department of Radiology, Osaka-Sayama (Japan); Nishino, Mizuki; Hatabu, Hiroto [Harvard Medical School, Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Boston, MA (United States); Gao, Wei [Boston University School of Public Health, Department of Biostatistics, Boston, MA (United States); Dupuis, Josee [Boston University School of Public Health, Department of Biostatistics, Boston, MA (United States); The National Heart Lung and Blood Institute' s Framingham Heart Study, Framingham, MA (United States); Hunninghake, Gary M.; Washko, George R. [Harvard Medical School, The Pulmonary and Critical Care Division, Brigham and Women' s Hospital, Boston, MA (United States); Murakami, Takamichi [Kinki University Faculty of Medicine, Department of Radiology, Osaka-Sayama (Japan); O' Connor, George T. [The National Heart Lung and Blood Institute' s Framingham Heart Study, Framingham, MA (United States); Boston University School of Medicine, Pulmonary Center and Department of Medicine, Boston, MA (United States)

2016-01-15

To investigate CT appearance and size of the thymus in association with participant characteristics. 2540 supposedly healthy participants (mean age 58.9 years, 51 % female) were evaluated for the CT appearance of thymic glands with four-point scores (according to the ratio of fat and soft tissue), size and morphology. These were correlated with participants' age, sex, BMI and smoking history. Of 2540 participants, 1869 (74 %) showed complete fatty replacement of the thymus (Score 0), 463 (18 %) predominantly fatty attenuation (Score 1), 172 (7 %) half fatty and half soft-tissue attenuation (Score 2) and 36 (1 %) solid thymic gland with predominantly soft-tissue attenuation (Score 3). Female participants showed less fatty degeneration of the thymus with higher thymic scores within age 40-69 years (P < 0.001). Participants with lower thymic scores showed higher BMI (P < 0.001) and were more likely to be former smokers (P < 0.001) with higher pack-years (P = 0.04). Visual assessment with four-point thymic scores revealed a sex difference in the fatty degeneration of the thymus with age. Women show significantly higher thymic scores, suggesting less fat content of the thymus, during age 40-69 years. Cigarette smoking and high BMI are associated with advanced fatty replacement of the thymus. (orig.)

Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

Science.gov (United States)

Fecher, Leslie A; Sharfman, William H

2015-01-01

Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

Carbon Ion irradiation in the treatment of grossly incomplete or unresectable malignant peripheral nerve sheaths tumors: acute toxicity and preliminary outcome

International Nuclear Information System (INIS)

Jensen, Alexandra D; Uhl, Matthias; Chaudhri, Naved; Herfarth, Klaus K; Debus, Juergen; Roeder, Falk

2015-01-01

To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST). We retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts). Median follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays). Carbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial

Radiotherapy in stage 3, unresectable, asymptomatic non-small cell lung cancer. Final results of a prospective randomized study of 240 patients

International Nuclear Information System (INIS)

Reinfuss, M.; Glinski, B.; Kowalska, T.; Kulpa, J.; Zawila, K.; Reinfuss, K.; Dymek, P.; Herman, K.; Skolyszewski, J.

1999-01-01

Purpose: to report the results of a prospective randomized study concerning the role of radiotherapy in the treatment of stage III, unresectable, asymptomatic non-small cell lung cancer. Material and methods: between 1992 and 1996, 240 patients with stage III, unresectable, asymptomatic non-small cell lung cancer were enrolled in this study, and sequentially randomized to one of the three treatment arms: conventional irradiation, hypo-fractionated irradiation and control group. In the conventional irradiation arm (79 patients), a dose of 50 Gy in 25 fractions in five weeks was delivered to the primary tumor and the mediastinum. In the hypo-fractionated irradiation arm (81 patients), there were two courses of irradiation separated by an interval of four weeks. In each series, patients received 20 Gy in five fractions in five days, in the same treatment volume as the conventional irradiation group. in the control group arm, 80 patients initially did not receive radiotherapy and were only observed. Delayed palliative hypo-fractionated irradiation (20-25 Gy in four to five fractions in four to five days) was given to the primary tumor when major symptoms developed. Results: the two-year actuarial survival rates for patients in the conventional irradiation, hypo-fractionated irradiation and control group arms were 18%, 6% and 0%, with a median survival time of 12 months, nine months and six months respectively. The differences between survival rates were statistically significant at the 0.05 level. Conclusion: although irradiation provides good palliation the results are disappointing. The comparison of conventional and hypo-fractionated irradiation shows an advantage for conventional schedules. (author)

Phase I study of cisplatin analogue nedaplatin, paclitaxel, and thoracic radiotherapy for unresectable stage III non-small cell lung cancer

International Nuclear Information System (INIS)

Sekine, Ikuo; Sumi, Minako; Ito, Yoshinori

2007-01-01

The standard treatment of unresectable stage III non-small cell lung cancer is concurrent chemoradiotherapy in patients in good general condition, but where the optimal chemotherapeutic regimen has not been determined. Patients with unresectable stage III non-small cell lung cancer received nedaplatin (80 mg/m 2 ) and paclitaxel on day 1 every 4 weeks for 3-4 cycles and concurrent thoracic radiotherapy (60 Gy/30 fractions for 6 weeks) starting on day 1. The dose of paclitaxel was escalated from 120 mg/m 2 in level 1, 135 mg/m 2 in level 2 to 150 mg/m 2 in level 3. A total of 18 patients (14 males and 4 females, with a median age of 62.5 years) were evaluated in this study. Full cycles of chemotherapy were administered in 83% of patients in level 1, and in 50% of patients in levels 2 and 3. No more than 50% of patients developed grade 4 neutropenia. Transient grade 3 esophagitis and infection were noted in one patient, and unacceptable pneumonitis was noted in three (17%) patients, two of whom died of the toxicity. Dose-limiting toxicity (DLT), evaluated in 15 patients, noted in one of the six patients in level 1, three of the six patients in level 2 and one of the three patients in level 3. One DLT at level 2 developed later as radiation pneumonitis. Thus, the maximum tolerated dose was determined to be level 1. The overall response rate (95% confidence interval) was 67% (41-87%) with 12 partial responses. The doses of paclitaxel and nedaplatin could not be escalated as a result of severe pulmonary toxicity. (author)

Adipocyte and leptin accumulation in tumor-induced thymic involution.

Science.gov (United States)

Lamas, Alejandro; Lopez, Elena; Carrio, Roberto; Lopez, Diana M

2016-01-01

Cell-mediated immunity is an important defense mechanism against pathogens and developing tumor cells. The thymus is the main lymphoid organ involved in the formation of the cell-mediated immune response by the maturation and differentiation of lymphocytes that travel from the bone marrow, through the lymphatic ducts, to become T lymphocytes. Thymic involution has been associated with aging; however, other factors such as obesity, viral infection and tumor development have been shown to increase the rate of shrinkage of this organ. The heavy infiltration of adipocyte fat cells has been reported in the involuted thymuses of aged mice. In the present study, the possible accumulation of such cells in the thymus during tumorigenesis was examined by immunohistochemistry. A significant number of adipocytes around and infiltrating the thymuses of tumor-bearing mice was observed. Leptin is a pro-inflammatory adipocytokine that enhances thymopoiesis and modulates T cell immune responses. The levels of leptin and adiponectin, another adipocytokine that has anti-inflammatory properties, were examined by western blot analysis. While no changes were observed in the amounts of adiponectin present in the thymuses of the normal and tumor-bearing mice, significantly higher levels of leptin were detected in the thymocytes of the tumor-bearing mice. This correlated with an increase in the expression of certain cytokines, such as interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). The co-culture of thymocytes isolated from normal mice with ex vivo isolated adipocytes from tumor-bearing mice yielded similar results. Our findings suggest that the infiltration and accumulation of adipocytes in the thymuses of tumor-bearing mice play an important role in their altered morphology and functions.

Advances in the targeted therapy of liposarcoma

Directory of Open Access Journals (Sweden)

Guan Z

2015-01-01

Full Text Available Zhonghai Guan,1 Xiongfei Yu,1 Haohao Wang,1 Haiyong Wang,1 Jing Zhang,1 Guangliang Li,2 Jiang Cao,3 Lisong Teng1 1Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, 2Department of Medicine Oncology, Zhejiang Cancer Hospital, 3Clinical Research Center, The 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: Liposarcoma (LPS is the most common type of soft-tissue sarcoma. Complete surgical resection is the only curative means for localized disease; however, both radiation and conventional cytotoxic chemotherapy remain controversial for metastatic or unresectable disease. An increasing number of trials with novel targeted therapy of LPS have provided encouraging data during recent years. This review will provide an overview of the advances in our understanding of LPS and summarize the results of recent trials with novel therapies targeting different genetic and molecular aberrations for different subtypes of LPS. Keywords: well-/dedifferentiated, myxoid/round cell, pleomorphic, soft-tissue sarcoma

Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok

2014-01-01

Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

2014-06-15

Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

Lineage Tracing and Cell Ablation Identify a Post-Aire-Expressing Thymic Epithelial Cell Population

Directory of Open Access Journals (Sweden)

Todd C. Metzger

2013-10-01

Full Text Available Thymic epithelial cells in the medulla (mTECs play a critical role in enforcing central tolerance through expression and presentation of tissue-specific antigens (TSAs and deletion of autoreactive thymocytes. TSA expression requires autoimmune regulator (Aire, a transcriptional activator present in a subset of mTECs characterized by high CD80 and major histocompatibility complex II expression and a lack of potential for differentiation or proliferation. Here, using an Aire-DTR transgenic line, we show that short-term ablation specifically targets Aire+ mTECs, which quickly undergo RANK-dependent recovery. Repeated ablation also affects Aire− mTECs, and using an inducible Aire-Cre fate-mapping system, we find that this results from the loss of a subset of mTECs that showed prior expression of Aire, maintains intermediate TSA expression, and preferentially migrates toward the center of the medulla. These results clearly identify a distinct stage of mTEC development and underscore the diversity of mTECs that play a key role in maintaining tolerance.

Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

Science.gov (United States)

2017-07-15

Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Pancreatic Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Gallbladder Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer

Perioperative Outcomes and Long-term Survival in Clinically Early-stage Thymic 
Malignancies: Video-assisted Thoracoscopic Thymectomy versus Open Approaches

Directory of Open Access Journals (Sweden)

Hao WANG

2016-07-01

Full Text Available Background and objective Video-assisted thoracoscopic surgery (VATS theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II thymic malignancies. However, longterm outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART. Methods Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group, while 876 cases underwent open thymectomy (Open group. Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs 73.9%, P=0.028, resection rate (98.8% vs 88.7%, P<0.001 and less recurrence (2.9% vs 16.0%, P<0.001. Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15. However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011. Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. Conclusion This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival.

Endoscopic Ultrasound-Guided Drainage of Intra-Abdominal Abscess after Gastric Perforation in a Patient Receiving Ramucirumab and Paclitaxel for Advanced Gastric Cancer

Directory of Open Access Journals (Sweden)

Koichiro Mandai

2017-01-01

Full Text Available Gastrointestinal perforation is a serious adverse event that occurs in approximately 1% of patients receiving ramucirumab and paclitaxel. A 67-year-old man with unresectable advanced gastric cancer was admitted to our hospital and treated with ramucirumab and paclitaxel. Gastric perforation occurred during the second cycle of chemotherapy. Although the patient’s condition improved without surgery, an abscess developed in the intra-abdominal fluid collection resulting from the perforation. We performed endoscopic ultrasound-guided abscess drainage. The patient improved and was discharged in satisfactory condition. Endoscopic ultrasound-guided drainage is a treatment option for patients with intra-abdominal abscess following gastric perforation due to ramucirumab.

Efficacy of preoperative radiochemotherapy in patients with locally advanced pancreatic carcinoma

International Nuclear Information System (INIS)

Lind, Pehr A.; Bystroem, Per; Isaksson, Bengt; Almstroem, Markus; Permert, Johan; Johnsson, Anders; Albiin, Nils

2008-01-01

Background. The optimal care for patients with unresectable, non-metastatic pancreatic adenocarcinoma (PAC) is debated. We treated 17 consecutive cases with preoperative radiochemotherapy (RCT) as a means for downstaging their tumours and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period. Methods. The patients had biopsy proven, unresectable, non-metastatic PAC which engaged ≥ 50% of the circumference of a patent mesenteric/portal vein for a distance ≥ 2 cm and/or 2 d1; capecitabine 2 000 mg/m 2 d1-14 q 3 w) followed by 3-D conformal radiotherapy (50.4 Gy; 1.8 Gy fractions) with reduced Xelox (d1-5 q 1 w X 6). Results. No incident of RCT-related CTC Grade 3-4 haematologic and six cases of non-haematologic side-effects were diagnosed. Sixteen patients completed the RCT and were rescanned with CT and reevaluated for surgery 4 weeks post-RCT. Five cases were diagnosed with new metastases to the liver. Eleven patients were accepted for surgery whereof eight underwent a curative R 0 -resection. The median overall survival for the latter group was 29 months, which compared favourably with our control group of patients undergoing direct curative surgery for primarily resectable PAC (median OS: 16 months; RO-rate: 75%). Perioperative morbidity was similar in the two cohorts but the duration of surgery was longer (576 vs. 477 min) and the op blood loss was greater (3288 vs. 1460 ml) in the RCT-cohort (p < 0.05). The 30-day mortality was zero in both groups. Conclusion. Preoperative RCT in patients with locally advanced PAC resulted in a high rate of curative resections and promising median survival in our treatment series. This trimodality approach merits further exploration in new studies, which are currently underway at our Dept

Impact of Intraluminal Brachytherapy on Survival Outcome for Radiation Therapy for Unresectable Biliary Tract Cancer: A Propensity-Score Matched-Pair Analysis

Energy Technology Data Exchange (ETDEWEB)

Yoshioka, Yasuo [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Ogawa, Kazuhiko, E-mail: kogawa@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Oikawa, Hirobumi [Department of Radiology, Iwate Medical University, Iwate (Japan); Onishi, Hiroshi [Department of Radiology, University of Yamanashi, Yamanashi (Japan); Kanesaka, Naoto [Department of Radiology, Tokyo Medical University, Tokyo (Japan); Tamamoto, Tetsuro [Department of Radiation Oncology, Nara Medical University of Medicine, Nara (Japan); Kosugi, Takashi [Department of Radiology, Hamamatsu University School of Medicine, Shizuoka (Japan); Hatano, Kazuo [Department of Radiation Oncology, Chiba Cancer Center, Chiba (Japan); Kobayashi, Masao [Department of Radiology, Jikei University School of Medicine, Tokyo (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Takayama, Makoto [Department of Radiology, Kyorin University School of Medicine, Tokyo (Japan); Takemoto, Mitsuhiro [Department of Radiology, Okayama University, Okayama (Japan); Karasawa, Katsuyuki [Department of Radiation Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo (Japan); Nagakura, Hisayasu [Department of Radiology, KKR Sapporo Medical Center, Hokkaido (Japan); Imai, Michiko [Department of Radiation Oncology, Iwata City Hospital, Shizuoka (Japan); Kosaka, Yasuhiro [Department of Radiation Oncology, Kobe City Medical Center General Hospital, Hyogo (Japan); Yamazaki, Hideya [Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto (Japan); Isohashi, Fumiaki [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Nemoto, Kenji [Department of Radiation Oncology, Yamagata University, Yamagata (Japan); Nishimura, Yasumasa [Department of Radiation Oncology, Kinki University Faculty of Medicine, Osaka (Japan)

2014-07-15

Purpose: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. Methods and Materials: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS), and local control (LC) was investigated. Results: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT– group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT– group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT– group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. Conclusions: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life.

Impact of Intraluminal Brachytherapy on Survival Outcome for Radiation Therapy for Unresectable Biliary Tract Cancer: A Propensity-Score Matched-Pair Analysis

International Nuclear Information System (INIS)

Yoshioka, Yasuo; Ogawa, Kazuhiko; Oikawa, Hirobumi; Onishi, Hiroshi; Kanesaka, Naoto; Tamamoto, Tetsuro; Kosugi, Takashi; Hatano, Kazuo; Kobayashi, Masao; Ito, Yoshinori; Takayama, Makoto; Takemoto, Mitsuhiro; Karasawa, Katsuyuki; Nagakura, Hisayasu; Imai, Michiko; Kosaka, Yasuhiro; Yamazaki, Hideya; Isohashi, Fumiaki; Nemoto, Kenji; Nishimura, Yasumasa

2014-01-01

Purpose: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. Methods and Materials: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS), and local control (LC) was investigated. Results: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT– group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT– group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT– group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. Conclusions: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life

Multimodal hypoxia imaging and intensity modulated radiation therapy for unresectable non-small-cell lung cancer: the HIL trial

Directory of Open Access Journals (Sweden)

Askoxylakis Vasileios

2012-09-01

Full Text Available Abstract Background Radiotherapy, preferably combined with chemotherapy, is the treatment standard for locally advanced, unresectable non-small cell lung cancer (NSCLC. The tumor response to different therapy protocols is variable, with hypoxia known to be a major factor that negatively influences treatment effectiveness. Visualisation of tumor hypoxia prior to the use of modern radiation therapy strategies, such as intensity modulated radiation therapy (IMRT, might allow optimized dose applications to the target volume, leading to improvement of therapy outcome. 18 F-fluoromisonidazole dynamic positron emission tomography and computed tomography (18 F-FMISO dPET-CT and functional magnetic resonance imaging (functional MRI are attractive options for imaging tumor hypoxia. Methods/design The HIL trial is a single centre study combining multimodal hypoxia imaging with 18 F-FMISO dPET-CT and functional MRI, with intensity modulated radiation therapy (IMRT in patients with inoperable stage III NSCLC. 15 patients will be recruited in the study. All patients undergo initial FDG PET-CT and serial 18 F-FMISO dPET-CT and functional MRI before treatment, at week 5 of radiotherapy and 6 weeks post treatment. Radiation therapy is performed as inversely planned IMRT based on 4D-CT. Discussion Primary objectives of the trial are to characterize the correlation of 18 F-FMISO dPET-CT and functional MRI for tumor hypoxia imaging in NSCLC and evaluate possible effects of radiation therapy on tumor re-oxygenation. Further objectives include the generation of data regarding the prognostic value of 18 F-FMISO dPET-CT and functional MRI for locoregional control, progression free survival and overall survival of NSCLC treated with IMRT, which will form the basis for larger clinical trials focusing on possible interactions between tumor oxygenation and radiotherapy outcome. Trial registration The ClinicalTrials.gov protocol ID is NCT01617980

Concomitant bid radiotherapy with cisplatin and 5-fluorouracil in unresectable carcinoma of the pharynx: 10 year's experience at the Centre Antoine Lacassagne; Radiotherapie bifractionnee et chimiotherapie par cisplatine et 5-fluoro-uracile concomitantes dans les carcinomes epidermoides localement evolues non resecables du pharynx: dix ans d'experience au centre Antoine Lacassagne

Energy Technology Data Exchange (ETDEWEB)

Magne, N.; Pivot, X.; Marcy, P.Y.; Chauvel, P.; Courdi, A.; Dassonville, O.; Possonnet, G.; Vallicioni, J.; Ettore, F.; Falewee, M.N.; Milano, G.; Santini, J.; Lagrange, J.L.; Schneider, M.; Demard, F.; Bensadoun, R.J. [Centre Antoine-Lacassagne, 06 - Nice (France)

2001-08-01

Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors. From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal internal between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21 -day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m{sup 2} (day 1) and 5-FU was given as 6-day continuous infusion (750 mg/m{sup 2}/day at 1. course; 430 mg/m{sup 2}/day at 2. and 3. courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy. Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 3 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall were the Karnofsky index (71% survival at 3

Immunologic mechanism of the suppressive effect of low dose radiation on thymic lymphoma induced by radiation

International Nuclear Information System (INIS)

Li Xiujuan; Yang Ying; Li Xiuyi; Liu Shuzheng

1999-01-01

To study immunologic mechanism of the suppressive effect of low dose radiation (LDR) on thymic lymphoma (TL) induced by high dose radiation (HDR). The authors adopted the model that C57BL/6J mice were administered whole body irradiation with 1.75 Gy X-rays one time every week for 4 weeks to induce TL. It was examined that splenic NK cytotoxic activity, IL-2 and γ-IFN secretion activity, peritoneal macrophage phagocytosis and its TNF-α secretion activity in mice with different dose 1 month after irradiation. The results showed that all the immunologic functions mentioned above in mice given 75 mGy 12 h before 1.75 Gy every time were higher than that in mice given only 1.75 Gy, and approached to the sham-irradiation mice. It suggested that the suppressive effect of LDR on TL induced by HDR may be related to the adaptive response induced by LDR and decreasing immunological functions damage caused by HDR

Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids.

Science.gov (United States)

Seet, Christopher S; He, Chongbin; Bethune, Michael T; Li, Suwen; Chick, Brent; Gschweng, Eric H; Zhu, Yuhua; Kim, Kenneth; Kohn, Donald B; Baltimore, David; Crooks, Gay M; Montel-Hagen, Amélie

2017-05-01

Studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPCs) through to mature T cells. Existing in vitro models induce T cell commitment from human HSPCs; however, differentiation into mature CD3 + TCR-αβ + single-positive CD8 + or CD4 + cells is limited. We describe here a serum-free, artificial thymic organoid (ATO) system that supports efficient and reproducible in vitro differentiation and positive selection of conventional human T cells from all sources of HSPCs. ATO-derived T cells exhibited mature naive phenotypes, a diverse T cell receptor (TCR) repertoire and TCR-dependent function. ATOs initiated with TCR-engineered HSPCs produced T cells with antigen-specific cytotoxicity and near-complete lack of endogenous TCR Vβ expression, consistent with allelic exclusion of Vβ-encoding loci. ATOs provide a robust tool for studying human T cell differentiation and for the future development of stem-cell-based engineered T cell therapies.

Use of yttrium-90 microspheres (TheraSphere) in a patient with unresectable hepatocellular carcinoma leading to liver transplantation: a case report.

Science.gov (United States)

Kulik, Laura M; Mulcahy, Mary F; Hunter, Russell D; Nemcek, Albert A; Abecassis, Michael M; Salem, Riad

2005-09-01

Prior to therapy, model for end stage liver disease (MELD) scoring, diagnostic imaging and tumor staging were performed in a patient with T3 HCC. The patient received an orthotopic liver transplant (OLT) 42 days after treatment. The explant specimen showed complete necrosis of the target tumor. Follow-up of this patient has demonstrated no evidence of recurrence. There was no life threatening or fatal adverse experiences related to treatment. This case report documents the natural course, history and outcome of a patient treated with yttrium-90 for unresectable HCC. The patient was downstaged from T3 to T2 and was subsequently transplanted.

New treatment strategy against advanced rectal cancer. Enzyme-targeting and radio-sensitization treatment under parallel use of TS-1

International Nuclear Information System (INIS)

Obata, Shiro; Yamanishi, Mikio; Katsumi, Shingo

2015-01-01

Preoperative chemoradiotherapy was applied to two cases of advanced rectal cancer. In addition, radiation sensitizers were injected to the lesion endoscopically at a pace of twice a week in order to enhance therapeutic effects (so-called enzyme-targeting and radio-sensitization treatment: KORTUC [Kochi Oxydol Radio-sensitization Treatment for Unresectable Carcinomas]). The flattening of the lesion shape was observed for both cases in a short period of time, then, Mile's and lateral lymphnode dissection was performed. The remnant of lesion was not pointed out in postoperative pathological specimens for both cases, and histological judgment after the treatment was ranked as Grade 3. In light of the better-than-expected results, this hospital is preparing for clinical trials, and planning to carefully accumulate the cases. As one of the curative treatment strategies against advanced rectal cancer, the authors are willing to make this KORTUC more objectively reliable as a safe and minimally invasive therapy. (A.O.)