Neuroendocrine Tumors: A Focus on Liver Metastatic Lesions

Energy Technology Data Exchange (ETDEWEB)

Limouris, Georgios S., E-mail: nucleard@aretaieio.uoa.gr [Athens University Medical Faculty, Nuclear Medicine Division, Radiology Department, Aretaieion University Hospital, Athens (Greece)

2012-02-28

Transhepatic radionuclide infusion has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan). Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabeled somatostatin analogs, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3 ± 0.3 GBq (∼160–180 mCi) of In-111-DTPA-Phe1-Pentetreotide, 10- to 12-fold in total, administered monthly or of 4.1 ± 0.2 GBq (∼105–116 mCi) of Y-90 DOTA TOC, threefold in total, or of 7.0 ± 0.4 GBq (∼178–200 mCi) of Lu-177 DOTA TATE, fourfold to sixfold in total (the choice of which being based on the tumor size, assessed by CT or MRI). Follow-up at monthly intervals has to be performed by means of ultrasonography (US). Treatment response has to be assessed according to the WHO criteria (RECIST or SWOG).

Stereotactic irradiation for metastatic brain tumor

International Nuclear Information System (INIS)

Nomura, Ryutaro

2017-01-01

First, this paper reviewed the latest findings of stereotactic irradiation (STI) for metastatic brain tumors. Then, it described the results of randomized controlled trials for single or a few (2-4) metastasis in the following comparison tests: (1) comparison between whole brain radiotherapy (WBRT) alone group and (WBRT + STI) group, (2) comparison between STI alone group and (STI + WBRT) group, (3) comparison between STI alone group and (tumorectomy + WBRT) group, (4) comparison between (STI + WBRT) group and (tumorectomy + WBRT) group, and (5) between (tumorectomy + WBRT) group and (tumorectomy + STI) group. Among these, STI alone without WBRT has obtained a certain consensus. Against multiple metastatic brain tumors of 5 or more, when considering cognitive impairment and QOL loss by adding WBRT, it is general consensus that STI alone may be sufficient. At the authors' institution, cyber knife (CK) was introduced in 2008 and nearly 300 stereotactic radiotherapy for metastatic brain tumors have been performed annually. By adopting a robot arm and development of a lesion tracking system, the positional correction against the deviation of the bone margin of the skull is guaranteed in real time to ensure accuracy during irradiation, and hypofractionated stereotactic irradiation becomes easier. (A.O.)

Metastatic extrapleural malignant solitary fibrous tumor presenting with hypoglycemia (Doege–Potter syndrome

Directory of Open Access Journals (Sweden)

Andrew J. Degnan, MD, MPhil

2017-03-01

Full Text Available We report a rare case of metastatic malignant solitary fibrous tumor (SFT that presented with hypoglycemia because of insulin growth factor-2 production. Initial workup included computed tomography imaging that revealed a large, partially necrotic liver mass, a hypervascular pancreatic head lesion, and 2 renal lesions. Following hepatic resection, pancreatic head resection and nephrectomy, all these lesions demonstrated pathological findings that were consistent with SFT. The patient also had a history of an intracranial mass that had been previously resected and treated with gamma knife therapy at an outside institution, which was found to also be SFT. Six months after initial pancreatic head resection, the patient developed a new lesion involving the pancreatic tail that was found to represent recurrent metastatic SFT. This case emphasizes the highly aggressive nature of extrapleural SFT, while rare, and the role of imaging in follow-up for disease recurrence.

Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

International Nuclear Information System (INIS)

Uchiyama, Bine; Satoh, Ken; Saijo, Yasuo

1998-01-01

Forty patients with metastatic brain tumors from primary lung cancer underwent radiosurgery (γ-knife). We retrospectively compared their prior treatment history, number of metastatic foci, and performance status, to evaluate the effects of, and indications for, γ-knife therapy. After both the primary and the metastatic tumors were controlled, performance status could be used as an index in the choice of γ-knife therapy. Our results demonstrate that repeated γ-knife radiosurgeries prolonged survival time. Gamma-knife radiosurgery improves quality of life and prognosis of patients with metastatic brain tumors. (author)

Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

International Nuclear Information System (INIS)

Hughes, Brett; Yip, Desmond; Goldstein, David; Waring, Paul; Beshay, Victoria; Chong, Guan

2004-01-01

The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred. This case illustrates that the brain can be a

Effect of two tumors (metastatic and non-metastatic) on tissue distribution of Ga-67 citrate in the rat

International Nuclear Information System (INIS)

Durakovic, A.

1985-01-01

The effect of metastatic and non-metastatic mammary adenocarcinoma on tissue distribution of Ga-67 citrate in Fischer female rats was studied. The homogenate (0.1 ml) of each tumor was injected subcutaneously in separate groups of rats and the animals were studied from day 2-30 after tumor homogenate implantation. All animals were injected with 30 μCi of Ga-67 citrate and sacrificed by halothane anethesia 48 hours later. Tissue samples of blood, lung, heart, liver, spleen, kidney, adrenal, stomach, small and large intestine, ovaries, and lymph nodes (popliteal, lumbar, and mediastinal) were obtained and counted in a gamma well counter. The control group consisted of four animals and tumor bearing groups of seven to eight animals at each time. Ga-67 uptake was increased in the liver (24 days) and in the popliteal lymph nodes on days 7, 10, and 18 in the metastatic tumor group (P<0.05). This probably represents Ga-67 uptake in the metastatic deposits in these organs. No difference was observed in non-metastatic tumor group

Peritumoral edema associated with metastatic brain tumor

International Nuclear Information System (INIS)

Shirotani, Toshiki; Takiguchi, Hiroshi; Shima, Katsuji; Chigasaki, Hiroo; Tajima, Atsushi; Watanabe, Satoru.

1992-01-01

Computed tomographic (CT) examinations were performed in 94 lesions of 50 patients with metastatic brain tumors. Peritumoral edema (A E ) and tumor area (A T ) were measured using the planimetric method on the CT scan films that demonstrated maximum size of the tumor. Then, the volume of the peritumoral edema (V E ) and the surface area of the tumor (S T ) were claculated from these data. Eighty-three brain lesions from lung cancers were subdivided into 49 adenocarcinomas, 11 squamous cell carcinomas, 16 small cell carcinomas and 7 large cell carcinomas. Eleven metastatic tumors from breast cancers were all adenocarcinomas. There was statistical correlation between the surface area of tumor and the volume of the peritumoral edema for the adenocarcinoma (r=0.4043, p E /S T ratios in small cell carcinomas were smaller then those in non-small cell carcinomas, when the volume of the tumor was larger than 10 mm 3 . Accordingly, we suggest that the volume of the peritumoral edema in the small cell carcinoma is generally smaller than that in others. (author)

Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

International Nuclear Information System (INIS)

Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

2012-01-01

The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

Anti-tumoral effect of recombinant vaccinia virus through US guided injection in a rabbit model of hepatic VX2 carcinoma

Energy Technology Data Exchange (ETDEWEB)

Oh, Jong Young; Park, Byeong Ho; Kang, Myong Jin; Cho, Jin Han; Choi, Jong Cheol; Choi, Sun Seob; Nam, Kyung Jin; Hwang, Tae Ho; Jeong, Jin Sook [College of Medicine, Dong-A University, Busan (Korea, Republic of)

2006-02-15

The purpose of this study was to evaluate the anti-tumoral effect of recombinant vaccinia virus (rVV) (Thymidine kinase (-)/GM-CSF (+)) that was administered as a US guided intratumoral injection in a rabbit model of hepatic VX2 carcinoma. VX2 carcinoma was implanted in the livers of 12 rabbits. US was performed at every week interval to detect hepatic mass after the implantation of VX2 carcinoma. The accurate tumor size and volume was evaluated with CT when the tumor was detected on US. US guided injection of rVV (10{sup 9} pfu/ml) was preformed in three rabbits, intravenous injection of the same dose of rVV was done in two rabbits and another seven rabbits that were without any treatment were selected as a control group. We evaluated the change of the hepatic tumor size and extrahepatic metastasis on serial CT. Tumor specimens were harvested from rabbits that were killed at 8 weeks after VX2 implantation. These tissues were histoimmuopathologically compared to each other (the virus injection group and the control group). The differences between these groups were statistically assessed with student t-tests. Tumor growth was significantly suppressed in the US guided injection group compared with the intravenous injection group or the control group ({rho} < 0.01). The intravenous injection group showed statistically significant tumor suppression compared to the control group ({rho} < 0.01) until 2 weeks after virus injection. Quantification of the pulmonary metastatic nodules was performed in view of both the number and volume. The average number or volume of the pulmonary metastatic nodules in the US injection group was much smaller than these in the control group. Histopathologically, the tumors of the US guided injection group showed less extensive necrosis than those of the control group. Immunohistochemically, the tumor of the US guided injection group showed more prominent infiltration of CD4 (+) and CD8 (+) lymphocytes than did the tumors of the other group

Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

Science.gov (United States)

2017-04-18

Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

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 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

Local recurrence of metastatic brain tumor after surgery

International Nuclear Information System (INIS)

Shinoura, Nobusada; Yamada, Ryoji; Okamoto, Koichiro; Nakamura, Osamu; Shitara, Nobuyuki; Karasawa, Katsuyuki

2006-01-01

We analyzed factors associated with the local recurrence of brain metastases after surgery. Forty-seven patients with 67 metastatic brain tumors underwent surgery between 1994 and 2001. The survival time in the ''no recurrence'' group (34.7 months) was significantly longer than that in the recurrence group (21.9 months) (p=0.0008; log rank test). The factors affecting the local recurrence of brain metastases after surgery were as follows: cyst (p=0.0156), dural invasion (p=0.0029) of tumors, failure to totally remove tumors (p=0.0040), and lack of post-surgical irradiation (p<0.0001). Sex, age, tumor histology, tumor size, pre-surgical radiation, dose (≥45 vs <45, ≥50 vs <50 Gy) and the method (local vs whole brain) of post-surgical radiation did not affect the local recurrence rate of brain metastases after surgery. To avoid early recurrences of metastatic brain tumors, the factors associated with local recurrence should be considered in providing optimal treatment of tumors by surgery. (author)

Specific extracellular matrix remodeling signature of colon hepatic metastases.

Directory of Open Access Journals (Sweden)

Maguy Del Rio

Full Text Available To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.

Evaluation of the vascular state of hepatic tumor with radioisotope angiography and blood pool scintigraphies (early and delayed)

International Nuclear Information System (INIS)

Aburano, Tamio; Tonami, Norihisa; Hisada, Kinichi

1976-01-01

Combined radioisotope examinations of hepatic tumors have been performed using α 1 -fetoprotein radioimmunoassay, radioisotope angiography of the liver, and some tumor positive imaging scintigraphies. However, with these methods, it is frequently impossible to differentiate metastatic cancers from benign focal lesions. Radioisotope angiography of the liver, and both early (5 min later)- and delayed (4 hours later) blood pool scintigraphies of the liver were done continuously after 10mCi of sup(99m)Tc-albumin intravenous injection, in cases of clearcut focal lesions on sup(99m)Tc-colloid liver scan. The relationships among these findings were examined. Four of seven cases with hepatoma and two of nine cases with metastatic cancer which had showed hypervascular findings on radioisotope angiogram showed clear blood pool activities in the area of focal defects on sup(99m)Tc-colloid scan although less than liver. On the other hand, none of hypovascular tumors on radioisotope angiogram showed blood pool activities. However, four hours later, in most malignant lesions, the lesion to liver activity ratio calculated from data processing system showed a much higher value than the ratio obtained 5 min later after injection, although two cases with benign focal lesions did not show such sequential change. The sequential evaluation of the vascular state of a hepatic tumor using radioisotope angiography and early-and delayed blood pool scintigraphies was supposed to be extremely useful for the elucidation of the nature of focal hepatic lesions on sup(99m)Tc-colloid scan, especially in differentiating hypovascular malignant- and benign lesions. (auth.)

Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

Directory of Open Access Journals (Sweden)

Waring Paul

2004-10-01

Full Text Available Abstract Background The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. Case presentation A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression

Liver transplantation for metastatic neuroendocrine tumor: A case report and review of the literature

Institute of Scientific and Technical Information of China (English)

Wojciech C Blonski; K Rajender Reddy; Abraham Shaked; Evan Siegelman; David C Metz

2005-01-01

Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term "carcinoid". Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases,alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocinbased chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived.Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver.However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or locoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.

Differential diagnosis between metastatic tumors and nonsolid benign lesions of the liver using ferucarbotran-enhanced MR imaging

Energy Technology Data Exchange (ETDEWEB)

Higashihara, Hiroki [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan)], E-mail: h-higashihara@radiol.med.osaka-u.ac.jp; Murakami, Takamichi [Department of Radiology, Kinki University School of Medicine 377-2 Oonohigashi, Osakasayama, Osaka 5898511 (Japan); Kim, Tonsok; Hori, Masatoshi; Onishi, Hiromitsu [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan); Nakata, Saki [Department of Radiology, Toyonaka Municipal Hospital, 4-14-1 Shibahara Chou, Toyonaka, Osaka 5608565 (Japan); Osuga, Keigo; Tomoda, Kaname; Nakamura, Hironobu [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan)

2010-01-15

Purpose: To evaluate ability of ferucarbotran-enhanced MR imaging (MRI) in differentiating metastases from nonsolid benign lesions of the liver according to signal-intensity characteristics. Materials and methods: Sixty-six consecutive patients, who had 138 focal hepatic lesions (26 cysts, 11 hemangiomas, and 101 metastases), underwent ferucarbotran-enhanced MRI. The signal-intensity pattern of each kind of lesion relative to the liver parenchyma on ferucarbotran-enhanced T2* and heavily T1-weighted gradient-echo images were assessed and categorized into the following three categories: high-intensity and iso-intensity, respectively (category A), high and low (category B), and iso- and low-intensity (category C). For category B, lesions were subdivided into two groups based on single-shot half-Fourier RARE images: category B1 (not significantly high-intensity) and category B2 (significantly high-intensity). Results: Category A had 11 hemangiomas and 2 metastatic tumors, category B1 had 97 metastatic tumors, category B2 had 2 metastatic tumors and 9 cysts, and category C had 17 cysts. When a tumor with a signal intensity of category A was considered to be hemangioma, category B1 metastasis, and category B2 and C cyst, the diagnostic accuracy for differentiating these lesions was 97% (134/138). Conclusion: The combination of signal-intensity pattern on ferucarbotran-enhanced T2*- and heavily T1-weighted gradient-echo MRI has ability to differentiate liver metastases from nonsolid benign lesions. However, T2-weighted single-shot half-Fourier RARE imaging should also be employed to achieve better performance.

Effectiveness of radiation therapy for metastatic spinal tumors producing neurologic impairment

International Nuclear Information System (INIS)

Yamamoto, Shuichiro; Nomoto, Satoshi; Imada, Hajime; Nakata, Hajime

2002-01-01

The purpose of this study was to evaluate the efficacy of radiation therapy (RT) for treating neurological impairment and improving quality of life (QOL) in patients with metastatic spinal tumors. From 1985 through 2001, 75 patients with metastatic spinal tumors were treated with RT. Neurologic status and Karnofsky performance status were assessed before and after RT. The rate of neurologic improvement was significantly higher in patients with radio-sensitive tumors (75%) than in patients with radio-resistant tumors (37%). Few patients with Karnofsky performance status less than 40% before RT had good QOL after RT. The response to RT did not differ significantly on the basis of duration of paralysis before RT. RT is useful for treating neurologic impairment caused by metastatic spinal tumors, particularly those that are radiosensitive. To have good QOL after RT, treatment should be started in the early stage of neurological impairment. (author)

Tumor ocular metastásico Metastatic ocular tumor

Directory of Open Access Journals (Sweden)

Martha G Domínguez Expósito

2004-06-01

Full Text Available El carcinoma metastásico del ojo es considerado la neoplasia maligna que más frecuente se encuentra de forma intraocular. Solo cerca del 10 % de las personas que tienen una o más lesiones metastásicas intraoculares son detectadas clínicamente antes de la muerte. A menudo, el carcinoma metastásico ocular es diagnosticado por el oftalmólogo ante la presencia de síntomas oculares. Las lesiones están localizadas con preferencia en coroides. Nos motivo a realizar la presentación de este caso la presencia de lesiones intraoculares múltiples tumorales metastásicos en un paciente cuyo síntoma de presentación fue la disminución de la agudeza visualThe eye metastatic carcinoma is considered the most frequently found intraocular malignant neoplasia. Only 10 % of the persons with one or more metastatic intraocular injuries are clinically detected before death. The metastatic ocular carcinoma is often diagnosed by the ophthalmologist in the presence of ocular symptoms. The injuries are preferably located in the choroid. The appearance of multiple metastatic intraaocular tumoral injuries in a patient whose chief complaint was the reduction of visual acuity motivated us to presente this case

Microcirculation of the liver and hepatic tumors: implication for intervention

International Nuclear Information System (INIS)

Matsui, O.

2012-01-01

Full text:To understand the microcirculation of the liver and hepatic tumors is important for the precise imaging diagnosis and intervention of hepatic diseases. In this presentation, blood flow imaging features of dynamic MDCT in various hepatic lesions or variations as described below will be discussed based on the angiography-assisted CT imaging and pathophysiologic correlations. (1) Portal venous obstruction (segmental staining) and microangioarchtecture of the liver; Because of compensatory blood flow from the hepatic artery to the distal portion of the portal vein through the peribiliary vascular plexus (PBP), the obstructed segment shows early enhancement on dynamic CT (segmental staining). In diffuse intrahepatic portal vein obstruction, peripheral (zone) enhancement can be seen, resulting in 'central hypertrophy' in chronic stage. (2) Pseudolesion and/or pseudotumor due to third inflow into the liver; According to CT during arterial portography (CTAP)-based analysis, the third inflow includes flow from an aberrant right gastric vein (or pancreatico-duodeno-gastric vein), cystic veins, veins of Sappey, and aberrant left gastric vein. These veins usually connect directly to the intrahepatic portal venules. The areas receiving the third inflow often show pseudolesions or pseudotumors. (3) Microcirculation of hepatocellular carcinoma (HCC) and dynamic MDCT features; By single level dynamic thin-section CT during the bolus injection of a small amount of contrast medium, we revealed in vivo hemodynamics in hypervascular classical HCC, namely, the arterial blood flow into the tumor drains into surrounding hepatic sinusoids (corona enhancement, wash out). Histological examination revealed continuity between a tumor sinusoid and a portal venule in the pseudocapsule (encapsulated HCC) or surrounding hepatic sinusoids (HCC without pseudocapsule). The drainage area is the first site of the intrahepatic metastasis of HCC, and daughter nodules are commonly seen in this

Aggressive palliative surgery in metastatic phyllodes tumor: Impact on quality of life

Directory of Open Access Journals (Sweden)

A S Kapali

2010-01-01

Full Text Available Metastatic phyllodes tumor has very few treatment options. Phyllodes tumor in metastatic setting has limited role of surgery, radiotherapy and chemotherapy or combined treatment. Most of the patients receive symptomatic management only. We present a case of metastatic phyllodes tumor managed with aggressive margin negative resection of primary tumor leading to palliation of almost all the symptoms, which eventually led to improved quality of life and probably to improved survival. The improved quality of life was objectively assessed with Hamilton depression rating scale. Surgery may be the only mode of palliation in selected patients that provides a better quality of life and directly or indirectly may lead to improved survival.

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

Science.gov (United States)

Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia; Raoul, Jean-Luc

2017-01-01

In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

Tumor attributes predicting cutaneous metastatic destiny: a report of two interesting cases.

Science.gov (United States)

Gurumurthi, Ravichandran; Thirumalai, Raja; Easow, Jose M; Mohan, Subhashini

2014-07-01

Cutaneous metastases are the result of complex interaction between the tumor cells ("seed") and the host environment ("soil"). Metastases to the skin can be an early sign of internal malignancy or represent recurrence of the primary tumor and portends a poorer prognosis. Invasion and metastasis are the hallmarks of on cogenesis. Skin is the largest organ in the body, but the incidence of metastases is low. With advances in molecular biology, factors responsible for the initiation and perpetuation of metastatic tumor cells at distant sites are being elucidated. The concept of "pre-metastatic niche" and interaction between various chemokines has given a new outlook in understanding the organ specificity of metastatic tumor cells. We present two cases of cutaneous metastases with interesting clinical findings correlating with its biologic subtypes.

Study of perifocal low-density area in metastatic brain tumor

Energy Technology Data Exchange (ETDEWEB)

Suzuki, R; Okada, K; Hiratsuka, H; Inaba, Y [Tokyo Medical and Dental Univ. (Japan). School of Medicine; Tsuyumu, M

1980-04-01

It is well known that vasogenic brain edema often develops in brain tumors, head injuries, and inflammatory brain lesions. In order to investigate the development and resolution of vasogenic brain edema, some CT findings of metastatic brain tumors were studied in detail. 20 cases of metastatic brain tumors of the past three years were examined by means of a CT scan. In almost all the cases there was a perifocal low-density area (PFL) in the CT findings. In the tumors which were cystic and/or located in the infratentorial space, PFL was not present or, if present, only slightly so. On the contrary, in the tumors which were nodular and/or in the supratentorial space, PFL was present extensively. In the supratentorial metastasis, PFL seemed to be restricted within the white matter and not to involve the gray matter nor such midline structures as basal ganglia and corpus callosum. Besides, PFL was always in contact with the lateral ventricular wall. These results show that PFL in the metastatic tumors resembles in shape the experimental cold-induced brain edema in cats. PFL is presumed to represent vasogenic brain edema; these findings support the hypothesis that the main mechanism of the resolution of vasogenic brain edema is the drainage of the edema fluid into the ventricular CSF.

Diagnostic value of combined determination of serum AFP, CEA, CA199, SF levels in patients with primary hepatic carcinoma

International Nuclear Information System (INIS)

Wu Jiaming; Rui Zhilian

2005-01-01

Objective: To investigate the diagnostic value of combined detection of four tumor markers in patients with possible malignant change in liver disorders. Methods: Serum AFP, CEA, CA199 and SF levels were determined with chemiluminescence immunoassay (CLIA) in 49 patients with primary liver carcinoma, 7 patients with metastatic liver carcinoma, 40 patients with hepatic cirrhosis, 47 patients with HBV hepatitis and 30 controls. Results: The serum levels of AFP, CEA, SF in patients with primary hepatic cancer and serum levels of AFP, SF in patients with hepatic cirrhosis were all significantly higher than those in controls (P 0.05). Moreover, positive rate of combined determination of AFP, CEA, CA199, SF in patients with primary hepatic cancer was significantly higher than that in patients with metastatic liver cancer. Conclusion: With combined determination of these four tumor markers, the detection rate of primary hepatic carcinoma could be enhanced to above 95%. Also, differential diagnosis between primary and metastatic hepatic cancers could be facilitated. (authors)

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

Directory of Open Access Journals (Sweden)

Maeva Andriantsoa

Full Text Available In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP levels are frequently normal in cases of metastatic neuroendocrine tumor (NET.We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female, with a median age of 60 years (range: 28 to 84 years. The primary tumors were located in the duodenum/pancreas (n = 29, small bowel (n = 17 or colon/rectum (n = 3; 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients.Serum AP levels were elevated (≥ upper limit of normal (ULN in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010 and AP level (p = 0.017.Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

Detection of metastatic tumor in normal-sized retroperitoneal lymph nodes by monoclonal-antibody imaging

International Nuclear Information System (INIS)

Moldofsky, P.J.; Sears, H.F.; Mulhern, C.B. Jr.; Hammond, N.D.; Powe, J.; Gatenby, R.A.; Steplewski, Z.; Koprowski, H.

1984-01-01

Detection of metastatic colon carcinoma is reported in retroperitoneal lymph nodes that were visible but normal in size (less than 1 cm) and number on CT scanning and at surgery. A case history is presented of 1 of 27 patients with colon carcinoma, metastatic or primary, evaluated with intravenously administered, radiolabeled monoclonal-antibody fragments and subsequent nuclear medicine imaging. Images of /sup 99m/Tc-labeled red cells corresponding to each [ 131 I]antibody view of the abdomen were obtained as a control, to avoid interpretation of simple blood-pool radioactivity as specific localization of antibody on tumor. Antibody images were evaluated both without and with computer blood-pool image substraction. Directed to the level of the left renal hilum by the antibody scan, the surgeon removed the largest palpable node, which measured slightly less than 1 cm in diameter and was not palpably or visibly abnormal to the surgeon until it was removed and sectioned. Pathological evaluation of frozen and permanent sections revealed microscopic foci of adenocarcinoma consistent with a colonic primary tumor. Immunoperoxidase staining for the 1083-17-1A colorectal-carcinoma antigen demonstrated the presence of the antigen in the lymph node. As a result of the detection of this metastasis outside the liver, the patient did not receive the planned hepatic-artery chemotherapy pump but instead received intravenous chemotherapy

Gamma knife radiosurgery for metastatic brain tumors from lung cancer

Energy Technology Data Exchange (ETDEWEB)

Serizawa, Toru; Ono, Junichi; Iuchi, Toshihiko [Chiba Cardiovascular Center, Ichihara (Japan). Chiba Cancer Center] (and others)

2003-01-01

The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors ({>=} 3 cm) were surgically removed and all the other small lesions (<3 cm) were treated with GKS. New lesions were treated with repeated GKS. The tumor-progression-free, overall, neurological, lowered-QOL (quality of life)-free and new-lesion-free survivals were calculated with the Kaplan-Meier method. The poor prognostic factors for each survival were also analyzed with the Cox's proportional hazard model. The tumor control rate at 1 year was 96.5%. The estimated median overall survival time was 7.7 months. The first-year survival rates were 83.0% in neurological survival and 76.0% in lowered-QOL-free survival. The new-lesion-free survival at 1 year was 27.9%. Multivariate analysis revealed significant poor prognostic factors for neurological and lowered-QOL-free survivals were carcinomatous meningitis and >10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

Gene silencing in primary and metastatic tumors by small interfering RNA delivery in mice: quantitative analysis using melanoma cells expressing firefly and sea pansy luciferases.

Science.gov (United States)

Takahashi, Yuki; Nishikawa, Makiya; Kobayashi, Naoki; Takakura, Yoshinobu

2005-07-20

Silencing of oncogenes or other genes contributing to tumor malignancy or progression by RNA interference (RNAi) offers a promising approach to treating tumor patients. To achieve RNAi-based tumor therapy, a small interfering RNA (siRNA) or siRNA-expressing vector needs to be delivered to tumor cells, but little information about its in vivo delivery has been reported. In this study, we examined whether the expression of the target gene in tumor cells can be suppressed by the delivery of RNAi effectors to primary and metastatic tumor cells. To quantitatively evaluate the RNAi effects in tumor cells, mouse melanoma B16-BL6 cells were stably transfected with both firefly (a model target gene) and sea pansy (an internal standard gene) luciferase genes to obtain B16-BL6/dual Luc cells. The target gene expression in subcutaneous primary tumors of B16-BL6/dual Luc cells was significantly suppressed by direct injection of the RNAi effectors followed by electroporation. The expression in metastatic hepatic tumors was also significantly reduced by an intravenous injection of either RNAi effector by the hydrodynamics-based procedure. These results indicate that the both RNAi effectors have a potential to silence target gene in tumor cells in vivo when successfully delivered to tumor cells.

Combined therapy of radiation and hyperthermia on a metastatic tumor of angiosarcoma

International Nuclear Information System (INIS)

Yasuda, Hiroshi; Kitayama, Yoshiaki

1987-01-01

A combined therapy of radiation and hyperthermia is said to be fairly effective when applied to certain malignant tumors. However, the utility of this therapy for the treatment of angiosarcoma has not been well discussed. Recently, we have had a chance to treat a patient with metastatic angiosarcoma of the neck by using this combined therapy. In this paper, the clinical course of this patient and the availability of this combined therapy for angiosarcoma is reported. The patient was a 77-year-old man, having a primary lesion on the head and a metastatic tumor over the left cheek and neck. This combined therapy was used for the treatment of the metastatic tumor which caused severe pain and uncontrollable bleeding. The results were considered good ; the tumor decreased in size, pain disappeared and no further bleeding or severe side effects were observed. Though the patient died of another metastatic lesion which could not be treated with this combined therapy because the area of its localization could not allow placement in our hyperthermal apparatus, it is concluded that the combined therapy of radiation and hyperthermia is useful selectively for the treatment for angiosarcoma. (author)

MR imaging assessment of direct hepatic invasion by adjacent tumors

International Nuclear Information System (INIS)

Moeser, P.M.; Karstaedt, N.; Wolfman, N.T.; Bechtold, R.E.

1986-01-01

The proper staging of right renal and adrenal tumors requires accurate prediction of hepatic invasion. The authors retrospectively reviewed MR studies of 35 patients with right renal or adrenal masses to assess the utility of MR imaging in predicting direct hepatic invasion. Twenty-three patients were selected for study on the basis of absence of the fat plane between tumor and liver. Hepatic signal and tumor-liver interface characteristics were used to predict invasion. In 14 patients with renal tumors, absence of abnormal signal from hepatic parenchyma correlated well with absence of invasion, but the presence of abnormal hepatic signal did not necessarily indicate hepatic invasion. Inversion-recovery pulse sequences optimally demonstrated abnormal hepatic signal as well as the tumor-liver interface. The authors are currently reviewing the studies in the nine patients with adrenal masses

Metastatic papillary craniopharyngioma: case study and study of tumor angiogenesis.

Science.gov (United States)

Elmaci, Lhan; Kurtkaya-Yapicier, Ozlem; Ekinci, Gazanfer; Sav, Aydin; Pamir, M. Necmettin; Vidal, Sergio; Kovacs, Kalman; Scheithauer, Bernd W.

2002-01-01

We report a case of suprasellar papillary craniopharyngioma metastatic to the temporoparietal region 2 years after its initial resection. The literature documents examples of craniopharyngioma recurrences along the surgical tract, as well as remote ipsi- and contralateral metastases via cerebrospinal fluid seeding. Ours is the second report of a craniopharyngioma of papillary type to exhibit metastatic behavior. The tumor spread opposite the side of craniotomy. Although a rare occurrence, it confirms the limited capacity of histologically benign craniopharyngiomas to undergo meningeal seeding, likely the result of surgical manipulation. Immunohistochemical demonstration of increased microvascular density and vascular endothelial growth factor expression, as well as a high vascular endothelial growth receptor (VEGFR2) signal by in situ hybridization, suggests that tumor vascularity facilitated angiogenesis and may have been involved in the establishment and growth of the metastatic deposit. PMID:11916504

A study of perifocal low-density area in metastatic brain tumor

International Nuclear Information System (INIS)

Suzuki, Ryuta; Okada, Kodai; Hiratsuka, Hideo; Inaba, Yutaka; Tsuyumu, Matsutaira.

1980-01-01

It is well known that vasogenic brain edema often develops in brain tumors, head injuries, and inflammatory brain lesions. In order to investigate the development and resolution of vasogenic brain edema, some CT findings of metastatic brain tumors were studied in detail. 20 cases of metastatic brain tumors of the past three years were examined by means of a CT scan. In almost all the cases there was a perifocal low-density area (PFL) in the CT findings. In the tumors which were cystic and/or located in the infratentorial space, PFL was not present or, if present, only slightly so. On the contrary, in the tumors which were nodular and/or in the supratentorial space, PFL was present extensively. In the supratentorial metastasis, PFL seemed to be restricted within the white matter and not to involve the gray matter nor such midline structures as basal ganglia and corpus callosum. Besides, PFL was always in contact with the lateral ventricular wall. These results show that PFL in the metastatic tumors resembles in shape the experimental cold-induced brain edema in cats. PFL is presumed to represent vasogenic brain edema; these findings support the hypothesis that the main mechanism of the resolution of vasogenic brain edema is the drainage of the edema fluid into the ventricular CSF. (author)

Tumor progression: analysis of the instability of the metastatic phenotype, sensitivity to radiation and chemotherapy

International Nuclear Information System (INIS)

Welch, D.R.

1984-01-01

The major complications for tumor therapy are 1) tumor spread (metastasis); 2) the mixed nature of tumors (heterogeneity); and 3) the capacity of tumors to evolve (progress). To study these tumor characteristics, the rat 13762NF mammary adenocarcinoma was cloned and studied for metastatic properties and sensitivities to therapy (chemotherapy, radiation and hyperthermia). The cell clones were heterogeneous and no correlation between metastatic potential and therapeutic sensitivities was observed. Further, these phenotypes were unstable during pasage in vitro; yet, the changes were clone dependent and reproducible using different cryoprotected cell stocks. To understand the phenotypic instability, subclones were isolated from low and high passage cell clones. The results demonstrated that 1) tumor cells are heterogeneous for multiple phenotypes; 2) tumor cells are unstable for multiple phenotypes; 3) the magnitude, direction and time of occurrence of phenotypic drift is clone dependent; 4) the sensitivity of cell clones to ionizing radiation (γ or heat) and chemotherapy agents is independent of their metastatic potential; 5) shifts in metastatic potential and sensitivity to therapy may occur simultaneously but are not linked; and 6) tumor cells independently diverge to form several subpopulations with unique phenotypic profiles

Bronchial arterial infusion versus bronchial combined pulmonary arterial infusion for pulmonary metastatic tumors

International Nuclear Information System (INIS)

Dong Sheng; Dong Weihua; Jia Ningyang; Zhang Dianbo; Xiao Xiangsheng

2008-01-01

Objective: To evaluate the pulmonary metastatic tumor response to different ways of transcatheter arterial infusion. Methods: Thirty-five patients with pulmonary metastatic tumors were randomized divided into two groups: 15 patients with 49 lesions treated with bronchial arterial infusion (BAI) and 20 patients with 65 lesions treated with bronchial arterial infusion (BM)combined with pulmonary arterial infusion (PAI). The therapeutic response was assessed by the WHO evaluation criteria. Results: The total effective rate(CR + PR) of BAI was 65.3% (32/49), PAI + BAI was 61.5%(40/65) showing no statistical difference. The median survival time of BAI was 9 mo, BAI + PAI was 11.5 mo, demonstrating no statistical significance. Conclusions: BAI should be the primary treatment for pulmonary metastatic tumor. (authors)

Metastatic tumor of the pancreas: helical CT findings

International Nuclear Information System (INIS)

Lee, Soon Jin; Lee, Won Jae; Lim, Hyo Keun; Kim, Seung Hoon; Kim, Kyeong Ah; Choi, Sang Hee; Jang, Hyun Jung; Lee, Ji Yeon

2000-01-01

To analyze the helical computed tomographic (CT) findings of distant metastatic tumors to the pancreas and to determine the differential points between these and primary pamcreatic carcinomas. We sruveyed 22 patients with metastatic tumor of the pancreas, proven on the basis of clinical and pathological findings. Seventeen patients were men, and five were women, and their ages ranged between 36 and 83 years. Their primary conditions were lung cancer (n=3D15), rectal cancer (n=3D2), melanoma of the foot, chondrosarcoma of the sacrum, cervical cancer, leiomyosarcoma of the uterus, and extragonadal choriocarcinoma of the mediastinum. We retrospectively reviewed the abdominal helical CT findings, analysing the number, location, size and attenuation of masses, as well as secondary change, which included dilatation of the pancreatic and biliary ducts and invasion of peripancreatic tissue or vessels. We also evaluated the differential findings of primary pancreatic cancer. Sixteen patients had a solitary focal mass, while in five, two masses were present. Among the 22 patients, low-density nodular masses were present in 21; in the other, in whom multiple metastasis from chondrosarcoma had occurred, there was dense calcification. The size of metastatic masses varied, ranging from 0.6 to 6 cm in diameter. The pancreatic duct proximal to the mass was dilated in ten cases, while the bile duct was dilated in six. The metastatic masses masses demonstrated no peripancreatic or vascular invasion, though they showed a discrete margin and contour bulging. Single metastasis to the pancreas was most common, and metastatic masses had a discrete margin, with contour bulging. There was no peripancreatic or vascular invasion. If the metastasis involved a single low-attenuated mass, however, with pancreatic or biliary dilatation, it was difficult to differentiate this from primary pancreatic cancer. (author)

Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization.

Science.gov (United States)

Sato, Kent; Lewandowski, Robert J; Bui, James T; Omary, Reed; Hunter, Russell D; Kulik, Laura; Mulcahy, Mary; Liu, David; Chrisman, Howard; Resnick, Scott; Nemcek, Albert A; Vogelzang, Robert; Salem, Riad

2006-01-01

In Canada and Europe, yttrium-90 microspheres (TheraSphere); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.

Multidisciplinary Approach to Hepatic Metastases of Intracranial Hemangiopericytoma: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Dimitrios K. Manatakis

2015-01-01

Full Text Available Hemangiopericytoma is a rare primary tumor originating from Zimmerman’s pericytes, with significant metastatic potential. Hepatic metastatic disease requires an aggressive approach by a multidisciplinary team of dedicated oncology specialists, to prolong survival in selected patients. We report on a patient with recurrent hepatic metastases of grade II intracranial hemangiopericytoma 5 years after initial treatment, managed by a stepwise combination of liver resection, radiofrequency ablation, and transarterial embolization. Although metastatic disease implies hematogenous dissemination, long-term survival after liver resection has been reported and major hepatectomies are justified in patients with adequate local control. Liver resections combined with transarterial embolization are highly recommended, due to hypervascularity of the tumor.

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

Science.gov (United States)

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

Interstitial laser immunotherapy for treatment of metastatic mammary tumors in rats

Science.gov (United States)

Figueroa, Daniel; Joshi, Chet; Wolf, Roman F.; Walla, Jonny; Goddard, Jessica; Martin, Mallory; Kosanke, Stanley D.; Broach, Fred S.; Pontius, Sean; Brown, Destiny; Li, Xiaosong; Howard, Eric; Nordquist, Robert E.; Hode, Tomas; Chen, Wei R.

2011-03-01

Thermal therapy has been used for cancer treatment for more than a century. While thermal effect can be direct, immediate, and controllable, it is not sufficient to completely eradicate tumors, particularly when tumors have metastasized locally or to the distant sites. Metastases are the major cause of treatment failure and cancer deaths. Current available therapies, such as surgery, radiation, and chemotherapy, only have limited curative effects in patients with late-stage, metastatic cancers. Immunotherapy has been considered as the ultimate approach for cancer treatment since a systemic, anti-tumor, immunological response can be induced. Using the combination of photothermal therapy and immunotherapy, laser immunotherapy (LIT),a novel immunotherapy modality for late-stage cancer treatment, has been developed. LIT has shown great promise in pre-clinical studies and clinical breast cancer and melanoma pilot trials. However, the skin color and the depth of the tumor have been challenges for effective treatment with LIT. To induce a thermal destruction zone of appropriate size without causing thermal damage on the skin, we have developed interstitial laser immunotherapy (ILIT) using a cylindrical diffuser. To determine the effectiveness of ILIT, we treated the DMBA-4 metastatic tumors in rats. The thermal damage in tumor tissue was studied using TTC immersion and hematoxolin and eosin (H & E) staining. Also observed was the overall survival of the treated animals. Our results demonstrated that the ILIT could impact a much larger tumor area, and it significantly reduced the surface damage compared with the early version of non-invasive LIT. The survival data also indicate that ILIT has the potential to become an effective tool for the treatment of deeper, larger, and metastatic tumors, with reduced side effects.

Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio

Directory of Open Access Journals (Sweden)

Dezarn William A

2007-03-01

Full Text Available Abstract Background Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres® Sirtex Medical, Lake Forest, IL were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment. Methods Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers. Results Of the 40 patients, 5 had hepatocellular cancer (HCC, and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma. All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks. Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4. Average administered activity was 1.2 GBq (0.4 to 2.4 GBq. Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy. Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy. None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 % had transient and 7 patients (17.5 % had persistent LFT abnormalities. There were 27 (67.5% responders (complete response, partial response, and stable disease. Tumor response correlated with higher tumor flow ratio as measured by

Ultrasonographic classification of Atypical hepatic hemangiomas

International Nuclear Information System (INIS)

Bae, Sang Jin; Kim, Pyo Nyun; Ha, Hyun Kwon; Lee, Moon Gyu; Auh, Yong Ho; Yoon, Kwon Ha

2000-01-01

Cavernous hemangioma is the most common benign hepatic tumor. Typically, the most common features revealed by ultrasound (US) include its small size (4 cm or less in diameter), uniform hyperechogenicity, well defined margins, position in the subcapsular region of the right lobe of the liver, and some posterior echo enhancement. In addition, follow-up scanning may reveal changes in size, though this is rare. The US findings of hepatic hemangiomas may vary, however, especially when lesions are large and/or multiple. For that reason, differential diagnosis between this condition and hepatocellular carcinomas, metastatic lesions, lymphomas and other tumors is difficult. An understanding of the various sonographic findings of hepatic hemangioma can facilitate the early detection of the condition. (author)

Murine macrophage heparanase: inhibition and comparison with metastatic tumor cells

International Nuclear Information System (INIS)

Savion, N.; Disatnik, M.H.; Nevo, Z.

1987-01-01

Circulating macrophages and metastatic tumor cells can penetrate the vascular endothelium and migrate from the circulatory system to extravascular compartments. Both activated murine macrophages and different metastatic tumor cells attach, invade, and penetrate confluent vascular endothelial cell monolayer in vitro, by degrading heparan sulfate proteoglycans in the subendothelial extracellular matrix. The sensitivity of the enzymes from the various sources degrading the heparan sulfate proteoglycan was challenged and compared by a series of inhibitors. Activated macrophages demonstrate a heparanase with an endoglycosidase activity that cleaves from the [ 35 S]O 4 - -labeled heparan sulfate proteoglycans of the extracellular matrix 10 kDa glycosaminoglycan fragments. The degradation of [ 35 S]O 4 - -labeled extracellular matrix proteoglycans by the macrophages' heparanase is significantly inhibited in the presence of heparan sulfate (10μg/ml), arteparon (10μg/ml), and heparin at a concentration of 3 μg/ml. Degradation of this heparan sulfate proteoglycan is a two-step sequential process involving protease activity followed by heparanase activity. B16-BL6 metastatic melanoma cell heparanase, which is also a cell-associated enzyme, was inhibited by heparin to the same extent as the macrophage haparanase. On the other hand, heparanase of the highly metastatic variant (ESb) of a methylcholanthrene-induced T lymphoma, which is an extracellular enzyme released by the cells to the incubation medium, was more sensitive to heparin and arteparon than the macrophages' heparanase. These results may indicate the potential use of heparin or other glycosaminoglycans as specific and differential inhibitors for the formation in certain cases of blood-borne tumor metastasis

Treatment of Unresectable Primary and Metastatic Liver Cancer with Yttrium-90 Microspheres (TheraSphere (registered) ): Assessment of Hepatic Arterial Embolization

International Nuclear Information System (INIS)

Sato, Kent; Lewandowski, Robert J.; Bui, James T.; Omary, Reed; Hunter, Russell D.; Kulik, Laura; Mulcahy, Mary; Liu, David; Chrisman, Howard; Resnick, Scott; Nemcek, Albert A.; Vogelzang, Robert; Salem, Riad

2006-01-01

In Canada and Europe, yttrium-90 microspheres (TheraSphere); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia

[Disseminated metastatic tumor at dorsal surface of medulla oblongata presenting intractable hiccups. A case report].

Science.gov (United States)

Arishima, Hidetaka; Kikuta, Ken-ichirou

2011-04-01

We report the case of disseminated metastatic tumor at dorsal surface of medulla oblongata presenting intractable hiccups. A 73-year-old man has a history of for metastatic lung tumor of the left tempral lobe. Although 3 surgeries and 4 radiotherapies were performed in the last 8 years, residual tumor grew slowly. He presented with intractable hiccups. His hiccups continued for 30 minutes, sometimes for 3 hours with obstruction of eating. Contrast-enhanced Magnetic resonance (MR) imaging demonstrated the dissemination of metastatic lung tumor at dorsal surface of medulla oblongata and ventral surface of midbrain. Some literatures reported the patients with intractable hiccups caused by dorsal medullary lesions. Therefore, we thought that the small disseminated tumor at dorsal surface of medulla oblongata caused the hiccups. Evaluation of dorsal medullay area by MR imaging is important to reveal the cause of intractable hiccups.

Heterogeneity of estrogen receptor expression in circulating tumor cells from metastatic breast cancer patients.

Directory of Open Access Journals (Sweden)

Anna Babayan

Full Text Available BACKGROUND: Endocrine treatment is the most preferable systemic treatment in metastatic breast cancer patients that have had an estrogen receptor (ER positive primary tumor or metastatic lesions, however, approximately 20% of these patients do not benefit from the therapy and demonstrate further metastatic progress. One reason for failure of endocrine therapy might be the heterogeneity of ER expression in tumor cells spreading from the primary tumor to distant sites which is reflected in detectable circulating tumor cells (CTCs. METHODS: A sensitive and specific staining protocol for ER, keratin 8/18/19, CD45 was established. Peripheral blood from 35 metastatic breast cancer patients with ER-positive primary tumors was tested for the presence of CTCs. Keratin 8/18/19 and DAPI positive but CD45 negative cells were classified as CTCs and evaluated for ER staining. Subsequently, eight individual CTCs from four index patients (2 CTCs per patient were isolated and underwent whole genome amplification and ESR1 gene mutation analysis. RESULTS: CTCs were detected in blood of 16 from 35 analyzed patients (46%, with a median of 3 CTCs/7.5 ml. In total, ER-negative CTCs were detected in 11/16 (69% of the CTC positive cases, including blood samples with only ER-negative CTCs (19% and samples with both ER-positive and ER-negative CTCs (50%. No correlation was found between the intensity and/or percentage of ER staining in the primary tumor with the number and ER status of CTCs of the same patient. ESR1 gene mutations were not found. CONCLUSION: CTCs frequently lack ER expression in metastatic breast cancer patients with ER-positive primary tumors and show a considerable intra-patient heterogeneity, which may reflect a mechanism to escape endocrine therapy. Provided single cell analysis did not support a role of ESR1 mutations in this process.

Heterogeneity of Estrogen Receptor Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients

Science.gov (United States)

Babayan, Anna; Hannemann, Juliane; Spötter, Julia; Müller, Volkmar

2013-01-01

Background Endocrine treatment is the most preferable systemic treatment in metastatic breast cancer patients that have had an estrogen receptor (ER) positive primary tumor or metastatic lesions, however, approximately 20% of these patients do not benefit from the therapy and demonstrate further metastatic progress. One reason for failure of endocrine therapy might be the heterogeneity of ER expression in tumor cells spreading from the primary tumor to distant sites which is reflected in detectable circulating tumor cells (CTCs). Methods A sensitive and specific staining protocol for ER, keratin 8/18/19, CD45 was established. Peripheral blood from 35 metastatic breast cancer patients with ER-positive primary tumors was tested for the presence of CTCs. Keratin 8/18/19 and DAPI positive but CD45 negative cells were classified as CTCs and evaluated for ER staining. Subsequently, eight individual CTCs from four index patients (2 CTCs per patient) were isolated and underwent whole genome amplification and ESR1 gene mutation analysis. Results CTCs were detected in blood of 16 from 35 analyzed patients (46%), with a median of 3 CTCs/7.5 ml. In total, ER-negative CTCs were detected in 11/16 (69%) of the CTC positive cases, including blood samples with only ER-negative CTCs (19%) and samples with both ER-positive and ER-negative CTCs (50%). No correlation was found between the intensity and/or percentage of ER staining in the primary tumor with the number and ER status of CTCs of the same patient. ESR1 gene mutations were not found. Conclusion CTCs frequently lack ER expression in metastatic breast cancer patients with ER-positive primary tumors and show a considerable intra-patient heterogeneity, which may reflect a mechanism to escape endocrine therapy. Provided single cell analysis did not support a role of ESR1 mutations in this process. PMID:24058649

Primary tumor resection in metastatic breast cancer: A propensity-matched analysis, 1988-2011 SEER data base.

Science.gov (United States)

Vohra, Nasreen A; Brinkley, Jason; Kachare, Swapnil; Muzaffar, Mahvish

2018-03-02

Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score-matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score-matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity-matched analysis. © 2018 Wiley Periodicals, Inc.

Radionuclide and X-ray diagnosis of metastatic tumors of the gastrointestinal tract. [/sup 198/Au; sup(99m)Tc; sup(113m)In

Energy Technology Data Exchange (ETDEWEB)

Makeev, A I; Ostrovtsev, I V; Roshchin, E M [Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Nauchnyj Tsentr

1982-02-01

A study was made of the spread of a tumor process in 161 patients with gastric cancer and in 9 patients with colorectal cancer. Diagnostic examinations preceeded treatment. The concentrations of the carcinoembryonic antigen (CEA) and ..cap alpha..- fetoprotein (AFP) in the blood plasma were demonstrated in 170 patients. Liver scanning was done to 122, and computerized tomography to 18 patients. It has been shown that the determination of the CEA level in the blood plasma can serve as an additional parameter to define tumor spread in the gastrointestinal tract. In gastric and colorectal cancer, a hepatic large focal lesion is accompanied by the highest CEA level. The CEA level and the gastric primary tumor mass show direct correlation. No correlation has been found between the AFP level and the degree of spread of a tumor process, both local and metastatic.

Extratumoral Heme Oxygenase-1 (HO-1 Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth.

Directory of Open Access Journals (Sweden)

Sofia Halin Bergström

Full Text Available Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1. To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer.

Investigation of Metastatic Breast Tumor Heterogeneity and Progression Using Dual Optical/SPECT Imaging

National Research Council Canada - National Science Library

Antich, Peter P; Constantinescu, Anca; Lewis, Matthew; Mason, Ralph; Richer, Edmond

2005-01-01

The goal of our project is to image tumor growth, metastatic development and vascular changes, both to characterize tumor dynamics during growth for application in diagnostic and prognostic imaging...

Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

International Nuclear Information System (INIS)

Cao Wei; Li Jing; Wu Zhiqun; Zhou Changxi; Liu Xi; Wan Yi; Duan Yunyou

2013-01-01

Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 °C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 °C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

Energy Technology Data Exchange (ETDEWEB)

Cao Wei, E-mail: cawe-001@163.com [Tangdu Hospital, The Fourth Military Medical University, Department of Interventional Radiology (China); Li Jing, E-mail: lijing02@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Burn and Plastic Surgery (China); Wu Zhiqun, E-mail: zhiqunwu@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Interventional Radiology (China); Zhou Changxi, E-mail: changxizhou@163.com [Chinese PLA General Hospital, Department of Respiratory Disease (China); Liu Xi, E-mail: xiliu@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Ultrasound Diagnostics (China); Wan Yi, E-mail: yiwan@163.com [The Fourth Military Medical University, Department of Health Statistics, Institute for Health Informatics (China); Duan Yunyou, E-mail: yunyouduan@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Ultrasound Diagnostics (China)

2013-06-15

Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 Degree-Sign C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 Degree-Sign C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

Tumor-infiltrating lymphocytes for the treatment of metastatic cancer

DEFF Research Database (Denmark)

Geukes Foppen, M H; Donia, M; Svane, I M

2015-01-01

five years, treatment with immunotherapy (anti CTLA-4, anti PD-1, or the combination of these antibodies) has shown very promising results and was able to improve survival in patients with metastatic melanoma. Adoptive cell therapy using tumor-infiltrating lymphocytes is yet another, but highly...

Detectability of metastatic bone tumor by Ga-67 scintigraphy

International Nuclear Information System (INIS)

Koizumi, Kiyoshi; Uchiyama, Guio; Araki, Tsutomu; Hihara, Toshihiko; Ogata, Hitoshi; Monzawa, Shuichi; Kachi, Kenji; Matsusako, Masaki

1989-01-01

Ga-67 scintigrams in patients with malignant diseases sometimes reveal uptake of the tracer in the bone metastases. Detectability of Ga-67 scintigraphy for metastatic bone tumors and benign bone lesions was compared with that of Tc-99m bone scintigraphy. Countable bone metastases detected by bone scintigraphy were evaluated whether the lesion showed apparent, faint, or negative Ga-67 uptake. Of 47 lesions 23 (49%) showed apparent uptake and 17 (36%) showed negative uptake, only 7 (10%) mostly fracture/osteotomy, showed apparent uptake of the tracer. Uptake in the other benign lesions such as trauma of the ribs, spondylosis deformans, and arthrosis deformans was rather faint. In patients with multiple bone metastases, 9 patients (82%) out of 11 showed more prominent abnormal findings in Tc-99m MDP bone scintigraphy than in Ga-67 scintigraphy; that is, Ga-67 scintigraphy was not able to reveal all metastatic bone lesions. In patients with untreated or recurrent tumors, relation between Ga-67 uptake in the tumors and that in the bone metastases was evaluated. Of 7 patients with negative Ga-67 uptake in the bone metastases; that is, there seemed to be little relation between Ga-67 affinity to the primary tumors and that to the bone metastases. Mechanisms of the Ga-67 uptake in the bone metastases were discussed. Not only the tumor cells or tissues in the bone metastases but also bone mineral or osteoclasts might be the deposition sites of Ga-67. (author)

Detectability of metastatic bone tumor by Ga-67 scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Koizumi, Kiyoshi; Uchiyama, Guio; Araki, Tsutomu; Hihara, Toshihiko; Ogata, Hitoshi; Monzawa, Shuichi; Kachi, Kenji; Matsusako, Masaki

1989-03-01

Ga-67 scintigrams in patients with malignant diseases sometimes reveal uptake of the tracer in the bone metastases. Detectability of Ga-67 scintigraphy for metastatic bone tumors and benign bone lesions was compared with that of Tc-99m bone scintigraphy. Countable bone metastases detected by bone scintigraphy were evaluated whether the lesion showed apparent, faint, or negative Ga-67 uptake. Of 47 lesions 23 (49%) showed apparent uptake and 17 (36%) showed negative uptake, only 7 (10%) mostly fracture/osteotomy, showed apparent uptake of the tracer. Uptake in the other benign lesions such as trauma of the ribs, spondylosis deformans, and arthrosis deformans was rather faint. In patients with multiple bone metastases, 9 patients (82%) out of 11 showed more prominent abnormal findings in Tc-99m MDP bone scintigraphy than in Ga-67 scintigraphy; that is, Ga-67 scintigraphy was not able to reveal all metastatic bone lesions. In patients with untreated or recurrent tumors, relation between Ga-67 uptake in the tumors and that in the bone metastases was evaluated. Of 7 patients with negative Ga-67 uptake in the bone metastases; that is, there seemed to be little relation between Ga-67 affinity to the primary tumors and that to the bone metastases. Mechanisms of the Ga-67 uptake in the bone metastases were discussed. Not only the tumor cells or tissues in the bone metastases but also bone mineral or osteoclasts might be the deposition sites of Ga-67.

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma

Directory of Open Access Journals (Sweden)

John E. Mullinax

2018-03-01

Full Text Available PurposeAdoptive cell therapy (ACT using tumor-infiltrating lymphocytes (TIL for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL.Experimental designThirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS, and overall survival (OS.ResultsAll patients received at least two doses of ipilimumab, and 12 of the 13 (92% received TIL. A median of 6.5 × 1010 (2.3 × 1010 to 1.0 × 1011 TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%, four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1–29.9 months. Grade ≥ 3 immune-related adverse events included hypothyroidism (3, hepatitis (2, uveitis (1, and colitis (1.ConclusionIpilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma.

Science.gov (United States)

Mullinax, John E; Hall, MacLean; Prabhakaran, Sangeetha; Weber, Jeffrey; Khushalani, Nikhil; Eroglu, Zeynep; Brohl, Andrew S; Markowitz, Joseph; Royster, Erica; Richards, Allison; Stark, Valerie; Zager, Jonathan S; Kelley, Linda; Cox, Cheryl; Sondak, Vernon K; Mulé, James J; Pilon-Thomas, Shari; Sarnaik, Amod A

2018-01-01

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Thirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS). All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 10 10 (2.3 × 10 10 to 1.0 × 10 11 ) TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%), four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1-29.9 months). Grade ≥ 3 immune-related adverse events included hypothyroidism (3), hepatitis (2), uveitis (1), and colitis (1). Ipilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Radiofrequency Ablation of Hepatic Cysts : Case Report

International Nuclear Information System (INIS)

Lee, Ye Ri; Kim, Pyo Nyun

2005-01-01

Radiofrequency ablation has been frequently performed on intra-hepatic solid tumor, namely, hepatocellular carcinoma, metastatic tumor and cholangio carcinoma, for take the cure. But, the reports of radiofrequency ablation for intrahepatic simple cysts are few. In vitro experiment of animal and in vivo treatment for intrahepatic cysts of human had been reported in rare cases. We report 4 cases of radiofrequency ablation for symptomatic intrahepatic cysts

Influence of WR-2721 on metastatic tumor spread after irradiation

International Nuclear Information System (INIS)

Ullrich, R.L.; Jernigan, M.C.; Yuhas, J.M.

1975-01-01

The Line 1 alveolar cell carcinoma is a transplantable murine tumor which, unlike most others, kills the host by means of metastatic spread. Attempts to cure this tumor with localized radiation therapy often fail, in spite of local tumor control, because the metastases evade the treatment. These facts suggest that host-tumor interactions may play a particularly important role in determining the ultimate survival of the tumor bearing animal. In order to initially evaluate the possible importance of normal regional tissues in host-tumor interactions the influence of WR-2721, a radioprotective drug, was examined for local tumor control and subsequent survival of the tumor bearing animal after localized radiation. Results indicated that WR-2721 can decrease metastasis. (U.S.)

Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

Science.gov (United States)

Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J; Korangy, Firouzeh; Greten, Tim F

2014-01-01

Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

Study on medical economic evaluation methods for metastatic brain tumors therapy

International Nuclear Information System (INIS)

Takura, Tomoyuki; Hayashi, Motohiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Uetsuka, Yoshio

2010-01-01

Treatment design for metastatic brain tumors is required to firstly care about the life and function for which the patient hopes because it is terminal care. Therefore, to discuss the value of the therapy, a viewpoint of the quality of life (QOL) and the socioeconomic factors other than the survival rate is important. However, examination that applies these factors to the therapy needs to be carried out more thoroughly. With this in mind, we discuss cost effectiveness of therapy for metastatic brain tumor, through a pilot study on gamma knife therapy. We studied 18 patients (mean age 61.6 years old) undergoing therapy for metastatic brain tumors. The health rate QOL was assessed by the profile-type measure SF-36 (Short-Form 36-Item Ver1.2) and the preference-based measure EQ-5D (EuroQoL-5D), before and six months after gamma knife therapy. Cost-utility-analysis (yen/Qaly) was carried out from quality adjusted life years (Qalys) and medical fee claims. In addition, we made a correlation analysis of the irradiation procedure and the gains attained. The observation by SF-36 for six months was useful for metastatic brain tumor. As a result, the QOL indicators showed increased mental health (MH: p=0.040) and role emotional (RE: p=0.029) with significant difference. In the measurement of EQ-5D, it was added only for one month based on the significant difference (p=0.022) from the pre-therapy QOL. The utilities that were analyzed became 0.052±0.175 standard deviation (SD) (score), and Qalys were 0.135. Because the cost was 721.4±5.2 SD (thousand yen), the performance of cost-utility-analysis was estimated as 5,330,000 (yen/Qaly). In addition, positive correlation (r=0.845/p=0.034) was found between the EQ-5D utility score and the tumor irradiation energy (mJ), etc. We established a new value over and above mere survival rate concerning metastatic brain tumor therapy. The socioeconomics and efficacy of therapy are more difficult to discuss in this disease than in other

Optical detection and virotherapy of live metastatic tumor cells in body fluids with vaccinia strains.

Directory of Open Access Journals (Sweden)

Huiqiang Wang

Full Text Available Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV. In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.

Surgical Control of a Primary Hepatic Carcinoid Tumor: A Case Report

Directory of Open Access Journals (Sweden)

Norio Yokoigawa

2009-04-01

Full Text Available We report a primary hepatic carcinoid tumor occurring in a 47-year-old man. The patient consulted our hospital complaining of epigastralgia. Abdominal ultrasonography, computed tomography scanning, and magnetic resonance imaging showed a large mass in the right lobe of the liver. FDG-PET revealed 18F-FDG uptake by the right hepatic lobe. The tumor was a solid mass with cystic components, approximately 15 cm in diameter. We conducted an extended right lobectomy of the liver. The resected specimen was a solid tumor with cystic components and hemorrhagic lesion. Microscopic findings showed that the tumor cells had round nuclei and formed trabecular patterns. Immunohistologically, tumor cells were stained positive for chromogranin A, neuron specific enolase, CD56, and S-100. Careful examinations before and after the operation revealed no other possible origin of the tumor. Based on these findings, the tumor was diagnosed as a primary hepatic carcinoid. This is a report of a rare case of a primary hepatic carcinoid tumor with a discussion of several other relevant reports.

Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor.

Science.gov (United States)

Vasselli, James R; Shih, Joanna H; Iyengar, Shuba R; Maranchie, Jodi; Riss, Joseph; Worrell, Robert; Torres-Cabala, Carlos; Tabios, Ray; Mariotti, Andra; Stearman, Robert; Merino, Maria; Walther, McClellan M; Simon, Richard; Klausner, Richard D; Linehan, W Marston

2003-06-10

To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor.

Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

Directory of Open Access Journals (Sweden)

Tobias Eggert

Full Text Available Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL, while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

Pseudo-tumoral hepatic tuberculosis discovered after surgical resection

Directory of Open Access Journals (Sweden)

Miloudi Nizar

2012-02-01

Full Text Available Pseudo-tumoral hepatic tuberculosis is rare. It is characterized by non-specific symptoms and radiological polymorphism. Diagnosis is problematic. This article presents three cases, each clinically different from each other, that illustrate how difficult diagnosis can be. The definitive diagnosis of pseudo-tumoral hepatic tuberculosis was reached on the basis of histological examination of surgical samples. Treatment of the disease based on appropriate anti-tubercular therapy generally gives a positive outcome.

Acoustic Radiation Force Impulse Elastography for Focal Hepatic Tumors: Usefulness for Differentiating Hemangiomas from Malignant Tumors

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Eun [Department of Radiology, Gyeongsang National University School of Medicine, Jinju 660-702 (Korea, Republic of); Lee, Jae Young [Department of Radiology and Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Bae, Kyung Soo [Department of Radiology, Gyeongsang National University School of Medicine, Jinju 660-702 (Korea, Republic of); Han, Joon Koo; Choi, Byung Ihn [Department of Radiology and Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of)

2013-07-01

The purpose of this study is to investigate whether acoustic radiation force impulse (ARFI) elastography with ARFI quantification and ARFI 2-dimensional (2D) imaging is useful for differentiating hepatic hemangiomas from malignant hepatic tumors. One-hundred-and-one tumors in 74 patients were included in this study: 28 hemangiomas, 26 hepatocellular carcinomas (HCCs), three cholangiocarcinomas (CCCs), 20 colon cancer metastases and 24 other metastases. B-mode ultrasound, ARFI 2D imaging, and ARFI quantification were performed in all tumors. Shear wave velocities (SWVs) of the tumors and the adjacent liver and their SWV differences were compared among the tumor groups. The ARFI 2D images were compared with B-mode images regarding the stiffness, conspicuity and size of the tumors. The mean SWV of the hemangiomas was significantly lower than the malignant hepatic tumor groups: hemangiomas, 1.80 ± 0.57 m/sec; HCCs, 2.66 ± 0.94 m/sec; CCCs, 3.27 ± 0.64 m/sec; colon cancer metastases, 3.70 ± 0.61 m/sec; and other metastases, 2.82 ± 0.96 m/sec (p < 0.05). The area under the receiver operating characteristics curve of SWV for differentiating hemangiomas from malignant tumors was 0.86, with a sensitivity of 96.4% and a specificity of 65.8% at a cut-off value of 2.73 m/sec (p < 0.05). In the ARFI 2D images, the malignant tumors except HCCs were stiffer and more conspicuous as compared with the hemangiomas (p < 0.05). ARFI elastography with ARFI quantification and ARFI 2D imaging may be useful for differentiating hepatic hemangiomas from malignant hepatic tumors.

The role of CT in diagnosing small hepatic tumors

International Nuclear Information System (INIS)

Usuki, Noriaki; Daikokuya, Hideo; Fukuda, Haruyuki; Saiwai, Shigeo; Nakajima, Hideyuki; Miyamoto, Takeshi; Kudo, Masatoshi

1992-01-01

Twenty-seven cases of small hepatic tumors were examined by MRI and CT (ICT). MRI was more sensitive than plain and contrast CT. But ICT could detect more small lesions than MRI. CT is not more superior modality than MRI untill ICT is performed. It is concluded ICT should be done when diagnosing small hepatic tumors by CT. (author)

Inflammatory angiomyolipoma of the liver: a rare hepatic tumor

Directory of Open Access Journals (Sweden)

Liu Yang

2012-09-01

Full Text Available Abstract Angiomyolipoma (AML is a rare mesenchymal neoplasm of the tumor, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle and adipose cells. Hepatic AML may demonstrate a marked histological diversity. We herein present one case of hepatic AML exhibiting prominent inflammatory cells in the background, which happened in a 61-year-old Chinese female patient, without signs of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background, including small lymphocytes, plasma cells, and eosnophils. The tumor cells were spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and arranged along the vessels or scattered among the inflammatory background. Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues. The tumor cells were positive immunostaining for HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor and deserves wider recognition for its occurrence as a primary hepatic tumor. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1828633072762370

A fundamental study of dynamic CT for hemodynamics in experimental hepatic tumors

International Nuclear Information System (INIS)

Yamakawa, Fumiko

1991-01-01

Dynamic CT was performed using iodamide meglumine (2 ml/kg) to investigate hemodynamics in experimental hepatic tumors, tumor margins and in normal hepatic tissue as well in rabbits with VX 2 -induced hepatic tumors. Peak time (PT) and first moment (M1) were calculated from a time density curve prepared by eight consecutive 3-second scans over a period of 55 seconds. PT and M1 in tumors were significantly shorter than those in tumor margins and normal tissue, but were not influenced by tumor size. PT and M1 in tumor margins and normal tissue became longer with enlargement of the tumor. Ligation of the hepatic artery caused (1) no change in PT or M1 in normal tissue and tumor margins and (2) difficulty in measuring PT and M1 in tumors. Ligation of the portal vein caused (1) difficulty in measuring PT and M1 in normal tissue and tumor margins and (2) no change in PT or M1 in tumors. Pathological studies of specimens taken from each region of interest (ROI) showed that hemodynamics in the tumors reflected tumor-specific vascular structures. (author)

SR-1000 radiofrequency chemo-hyperthermia for recurrent and metastatic peritoneo-pelvic malignant tumors

International Nuclear Information System (INIS)

Luo Jingwei; Xiong Jinghong; Xu Guozhen; Yu Zihao; Li Yexiong; Yin Weibo

2002-01-01

Objective: To evaluate the efficacy and tolerance of intraperitoneal chemo-hyperthermia (IPCH) with SR-1000 radiofrequency (RF) for recurrent or metastatic peritoneo-pelvic malignant tumors. Methods: Twenty-one patients with recurrent or metastatic peritoneo-pelvic malignant tumors received chemo-hyperthermia, with 9 having local pain and 14 having ascites. The Karnofsky scores were 40-80. After abdominal cavity aspiration and infusion of hot NS and chemotherapeutic agents, the temperature of abdominal cavity was increased and maintained at 40.5-42.5 degree C for 60-90 minutes with SR-1000 RF. Hyperthermia was given twice per week and chemotherapy once per week, with the whole treatment lasting for 2-4 weeks. The commonly used drugs were DDP, MMC, 5-FU and so on. Results: Local pain was relieved in 8 of 9 patients, complete disappearance of ascites in 10 of 14. The common side-effects were fat necrosis (14.3%) and abdominal pain (24.8%). Conclusions: Intraperitoneal chemo-hyperthermia with SR-1000 RF appears to be a promising new approach for patients with recurrent or metastatic peritoneo-pelvic malignant tumors, especially for those who did not response to systemic chemotherapy or whose tumor recurred after chemotherapy. As to bulky lesions, local supplementary radiotherapy should be given in order to obtain better local control

Cone-Beam Computed Tomography (CBCT) Hepatic Arteriography in Chemoembolization for Hepatocellular Carcinoma: Performance Depicting Tumors and Tumor Feeders

Energy Technology Data Exchange (ETDEWEB)

Lee, In Joon [National Cancer Center, Department of Radiology (Korea, Republic of); Chung, Jin Wook, E-mail: chungjw@snu.ac.kr; Yin, Yong Hu; Kim, Hyo-Cheol; Kim, Young Il; Jae, Hwan Jun; Park, Jae Hyung [Seoul National University College of Medicine, Seoul National University Hospital, Department of Radiology (Korea, Republic of)

2015-10-15

PurposeThis study was designed to analyze retrospectively the performance of cone-beam computed tomography (CBCT) hepatic arteriography in depicting tumors and their feeders and to investigate the related determining factors in chemoembolization for hepatocellular carcinoma (HCC).MethodsEighty-six patients with 142 tumors satisfying the imaging diagnosis criteria of HCC were included in this study. The performance of CBCT hepatic arteriography for chemoembolization per tumor and per patient was evaluated using maximum intensity projection images alone (MIP analysis) or MIP combined with multiplanar reformation images (MIP + MPR analysis) regarding the following three aspects: tumor depiction, confidence of tumor feeder detection, and trackability of tumor feeders. Tumor size, tumor enhancement, tumor location, number of feeders, diaphragmatic motion, portal vein enhancement, and hepatic artery to parenchyma enhancement ratio were regarded as potential determining factors.ResultsTumors were depicted in 125 (88.0 %) and 142 tumors (100 %) on MIP and MIP + MPR analysis, respectively. Imaging performances on MIP and MIP + MPR analysis were good enough to perform subsegmental chemoembolization without additional angiographic investigation in 88 (62.0 %) and 128 tumors (90.1 %) on per-tumor basis and in 43 (50 %) and 73 (84.9 %) on per-patient basis, respectively. Significant determining factors for performance in MIP + MPR analysis on per tumor basis were tumor size (p = 0.030), tumor enhancement (0.005), tumor location (p = 0.001), and diaphragmatic motion (p < 0.001).ConclusionsCBCT hepatic arteriography provided sufficient information for subsegmental chemoembolization by depicting tumors and their feeders in the vast majority of patients. Combined analysis of MIP and MPR images was essential to enhance the performance of CBCT hepatic arteriography.

Pediatric hepatic rhabdoid tumor: A rare cause of abdominal mass in children

Directory of Open Access Journals (Sweden)

Nicole Kapral, MD

2018-06-01

Full Text Available Pediatric hepatic rhabdoid tumors are rare tumors of the liver, with few cases reported in the literature. These aggressive tumors can be difficult to differentiate from hepatoblastomas on imaging alone, and surgical biopsy combined with special immunohistochemical stains can assist in differentiating these 2 tumor types. We present a case of hepatic rhabdoid tumor in a 7-month-old female infant, which was originally thought to be a hepatoblastoma; however, using BAF47 staining for INI-1 we were able to diagnose a rhabdoid tumor and affect the patient's medical oncologic therapy. Earlier detection and a better understanding of the imaging features of hepatic rhabdoid tumor may aid in improved patient management and treatment planning. Keywords: Rhabdoid tumor, INI-1, Hepatoblastoma, Pediatric, Rhabdomyosarcoma

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.

Science.gov (United States)

Adalsteinsson, Viktor A; Ha, Gavin; Freeman, Samuel S; Choudhury, Atish D; Stover, Daniel G; Parsons, Heather A; Gydush, Gregory; Reed, Sarah C; Rotem, Denisse; Rhoades, Justin; Loginov, Denis; Livitz, Dimitri; Rosebrock, Daniel; Leshchiner, Ignaty; Kim, Jaegil; Stewart, Chip; Rosenberg, Mara; Francis, Joshua M; Zhang, Cheng-Zhong; Cohen, Ofir; Oh, Coyin; Ding, Huiming; Polak, Paz; Lloyd, Max; Mahmud, Sairah; Helvie, Karla; Merrill, Margaret S; Santiago, Rebecca A; O'Connor, Edward P; Jeong, Seong H; Leeson, Rachel; Barry, Rachel M; Kramkowski, Joseph F; Zhang, Zhenwei; Polacek, Laura; Lohr, Jens G; Schleicher, Molly; Lipscomb, Emily; Saltzman, Andrea; Oliver, Nelly M; Marini, Lori; Waks, Adrienne G; Harshman, Lauren C; Tolaney, Sara M; Van Allen, Eliezer M; Winer, Eric P; Lin, Nancy U; Nakabayashi, Mari; Taplin, Mary-Ellen; Johannessen, Cory M; Garraway, Levi A; Golub, Todd R; Boehm, Jesse S; Wagle, Nikhil; Getz, Gad; Love, J Christopher; Meyerson, Matthew

2017-11-06

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.

Utility of bolus dynamic CT for the detection of hypervascular malignant hepatic tumors. Mainly referring to the comparison with delayed phase contrast-enhanced CT

International Nuclear Information System (INIS)

Matsuda, Hiromichi; Abe, Kimihiko; Freeny, P.C.

1996-01-01

In order to analyze the usefulness of dynamic contrast-enhanced CT, 84 patients who had hepatocellular carcinoma or suspected hypervascular metastases were studied with conventional incremental dynamic CT (CID-CT) or double helical CT (DH-CT). Delayed phase contrast-enhanced CT studies were consecutively performed in all patients. Thirty-six of 84 patients had malignant hepatic neoplasms; six had hepatocellular carcinoma and 30 had metastatic tumors. At first, the detectability of hepatic lesions was evaluated with bolus dynamic CT and delayed phase CT. Dynamic CT has detected more lesions than delayed CT. Some hepatic lesions described as isodensity were missed on CID-CT. Therefore, delayed phase CT cannot be eliminated when CID-CT is performed. Secondly, hepatic lesion detectability with CID-CT was compared with that of DH-CT. DH-CT did not miss the hepatic lesions picked up by delayed phase CT and was expected to provide excellent detectability of hypervascular hepatic neoplasms. In addition, first helical CT showed most hepatic lesions as areas of obvious hyperdensity, while CID-CT did not show their correct vascularities. So-called hypervascular hepatic tumors, however, were not always hypervascular and were demonstrated as areas of iso-hypodensity even on initial helical scanning. Second helical CT was useful to detect these so-called hypervascular, but actually hypovascular lesions. In conclusion, dynamic CT was helpful in detecting hypervascular hepatic malignant neoplasms, and DH-CT was more accurate than-CID-CT for the detection of hepatic lesions and the evaluation of vascular lesion. (author)

Outcome for children with metastatic solid tumors over the last four decades.

Directory of Open Access Journals (Sweden)

Stephanie M Perkins

Full Text Available Outcomes for pediatric solid tumors have significantly improved over the last 30 years. However, much of this improvement is due to improved outcome for patients with localized disease. Here we evaluate overall survival (OS for pediatric patients with metastatic disease over the last 40 years.The United States Surveillance, Epidemiology, and End Results (SEER database was used to conduct this study. Patients diagnosed between 0 and 18 years of age with metastatic Ewings sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma or Wilms tumor were included in the analysis.3,009 patients diagnosed between 1973-2010 met inclusion criteria for analysis. OS at 10 years for patients diagnosed between 1973-1979, 1980-1989, 1990-1999 and 2000-2010 was 28.3%, 37.2%, 44.7% and 49.3%, respectively (p<0.001. For patients diagnosed between 2000-2010, 10-year OS for patients with Ewing sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma and Wilms tumor was 30.6%, 54.4%, 29.3%, 27.5%, and 76.6%, respectively, as compared to 13.8%, 25.1%, 13.6%, 17.9% and 57.1%, respectively, for patients diagnosed between 1973-1979. OS for neuroblastoma significantly increased with each decade. For patients with osteosarcoma and Ewing sarcoma, there was no improvement in OS over the last two decades. There was no improvement in outcome for patients with rhabdomyosarcoma or Wilms tumor over the last 30 years.OS for pediatric patients with metastatic solid tumors has significantly improved since the 1970s. However, outcome has changed little for some malignancies in the last 20-30 years. These data underscore the importance of continued collaboration and studies to improve outcome for these patients.

Unforeseen clonal evolution of tumor cell population in recurrent and metastatic dermatofibrosarcoma protuberans.

Directory of Open Access Journals (Sweden)

Ensel Oh

Full Text Available Dermatofibrosarcoma protuberans (DFSP is a very rare soft tissue sarcoma, generally of low-grade malignancy. DFSP is locally aggressive with a high recurrence rate, but metastasis occurs rarely. To investigate the mechanism of metastasis in DFSP, we analyzed the whole exome sequencing data of serial tumor samples obtained from a patient who had a 10-year history of recurrent and metastatic DFSP. Tracking various genomic alterations, namely somatic mutations, copy number variations, and chromosomal rearrangements, we observed a dramatic change in tumor cell population during the occurrence of metastasis in this DFSP case. The new subclone that emerged in metastatic DFSP harbored a completely different set of somatic mutations and new focal amplifications, which had not been observed in the primary clone before metastasis. The COL1A1-PDGFB fusion, characteristic of DFSP, was found in all of the serial samples. Moreover, the break position on the fusion gene was identical in all samples. Based on these observations, we suggest a clonal evolution model to explain the mechanism underlying metastasis in DFSP and identified several candidate target genes responsible for metastatic DFSP by utilizing The Cancer Genome Atlas database. This is the first study to observe clonal evolution in metastatic DFSP and provide insight for a possible therapeutic strategy for imatinib-resistant or metastatic DFSP.

Exosomes from metastatic cancer cells transfer amoeboid phenotype to non-metastatic cells and increase endothelial permeability: their emerging role in tumor heterogeneity.

Science.gov (United States)

Schillaci, Odessa; Fontana, Simona; Monteleone, Francesca; Taverna, Simona; Di Bella, Maria Antonietta; Di Vizio, Dolores; Alessandro, Riccardo

2017-07-05

The goal of this study was to understand if exosomes derived from high-metastatic cells may influence the behavior of less aggressive cancer cells and the properties of the endothelium. We found that metastatic colon cancer cells are able to transfer their amoeboid phenotype to isogenic primary cancer cells through exosomes, and that this morphological transition is associated with the acquisition of a more aggressive behavior. Moreover, exosomes from the metastatic line (SW620Exos) exhibited higher ability to cause endothelial hyperpermeability than exosomes from the non metastatic line (SW480Exos). SWATH-based quantitative proteomic analysis highlighted that SW620Exos are significantly enriched in cytoskeletal-associated proteins including proteins activating the RhoA/ROCK pathway, known to induce amoeboid properties and destabilization of endothelial junctions. In particular, thrombin was identified as a key mediator of the effects induced by SW620Exos in target cells, in which we also found a significant increase of RhoA activity. Overall, our results demonstrate that in a heterogeneous context exosomes released by aggressive sub-clones can contribute to accelerate tumor progression by spreading malignant properties that affect both the tumor cell plasticity and the endothelial cell behavior.

Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor.

Directory of Open Access Journals (Sweden)

Ester Rozenblum

Full Text Available A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY, and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs/mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found. A large number of focal copy number alterations (FCNAs were detected, including homozygous deletions (HDs targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements. Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis.

Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread.

Science.gov (United States)

Spreafico, Filippo; Bongarzone, Italia; Pizzamiglio, Sara; Magni, Ruben; Taverna, Elena; De Bortoli, Maida; Ciniselli, Chiara M; Barzanò, Elena; Biassoni, Veronica; Luchini, Alessandra; Liotta, Lance A; Zhou, Weidong; Signore, Michele; Verderio, Paolo; Massimino, Maura

2017-07-11

Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Candidate proteins were identified with Fisher's exact test and/or a univariate logistic regression model. Reverse phase protein array (RPPA), Western blot (WB), and ELISA were used in the training set and in an independent set of CFS samples (60 cases, 14 controls) to validate our discovery findings. Among the 558 non-redundant proteins identified by LC-MS/MS, 147 were missing from the CSF database at http://www.biosino.org. Fourteen of the 26 final top-candidate proteins were chosen for validation with WB, RPPA and ELISA methods. Six proteins (type 1 collagen, insulin-like growth factor binding protein 4, procollagen C-endopeptidase enhancer 1, glial cell-line derived neurotrophic factor receptor α2, inter-alpha-trypsin inhibitor heavy chain 4, neural proliferation and differentiation control protein-1) revealed the ability to discriminate metastatic cases from controls. Combining a unique dataset of CSFs from pediatric CNS tumors with a novel enabling nanotechnology led us to identify CSF proteins potentially related to metastatic status.

Rare Presentation of Metastatic Cystic Trophoblastic Tumor in a Patient Without Prior Chemotherapy

Directory of Open Access Journals (Sweden)

Michael L. Wang

2017-07-01

Full Text Available Cystic trophoblastic tumor (CTT is a rare testicular germ cell tumor (GCT predominantly seen in post-chemotherapy patients. It is prognostically similar to teratoma and requires no additional chemotherapy in the absence of a nonteratomatous GCT component. We report a case of metastatic CTT in a patient with primary testicular teratoma without prior chemotherapy. Retroperitoneal lymph node metastases contained teratoma, embryonal carcinoma, and CTT. The CTT was β-hCG positive and SALL4 negative by immunohistochemistry (IHC. CTT can arise in metastatic testicular GCT in treatment naïve patients. An important differential diagnosis is choriocarcinoma due to treatment implications, and SALL4 IHC may help.

Halofuginone Inhibits Angiogenesis and Growth in Implanted Metastatic Rat Brain Tumor Model-an MRI Study

Directory of Open Access Journals (Sweden)

Rinat Abramovitch

2004-09-01

Full Text Available Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF is a potent inhibitor of collagen type α1(I. In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI, we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001. Treatment with HF significantly prolonged survival of treated animals (142%; P = .001. In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05. Additionally, HF treatment inhibited vessel maturation (P = .03. Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

Feasibility of carbon-ion radiotherapy for re-irradiation of locoregionally recurrent, metastatic, or secondary lung tumors.

Science.gov (United States)

Hayashi, Kazuhiko; Yamamoto, Naoyoshi; Karube, Masataka; Nakajima, Mio; Tsuji, Hiroshi; Ogawa, Kazuhiko; Kamada, Tadashi

2018-03-02

Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon-ion radiotherapy who were treated with re-irradiation with carbon-ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy-three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon-ion radiotherapy was 52.8 Gy (relative biological effectiveness) and the median dose of re-irradiation was 66.0 Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 18 months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2-year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re-irradiation with carbon-ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re-irradiation with carbon-ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Radiology of neuroendocrine tumors

International Nuclear Information System (INIS)

Hako, R.; Hakova, H.; Gulova, I.

2011-01-01

Neuroendocrine tumors arise in the bronchopulmonary or gastrointestinal tract, but they can arise in almost any organ. The tumors have varied malignant potential depending on the site of their origin. Metastases may be present at the time of diagnosis, which often occurs at a late stage of the disease. Most NETs have nonspecific imaging characteristics. Imaging plays a pivotal role in the localization and staging of neuroendocrine tumors and in monitoring the treatment response. Imaging should involve multi-phase computed tomography, contrast material-enhanced magnetic resonance imaging, contrast-enhanced ultrasonography and other one. Hepatic metastatic disease in particular lends itself to a wide range of interventional treatment options. Transcatheter arterial embolization may be used alone or in combination with chemo embolization. Ablative techniques, hepatic cryotherapy and percutaneous ethanol injection may then be undertaken. A multidisciplinary approach to treatment and follow-up is important. (author)

The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population

International Nuclear Information System (INIS)

Özmen, Evrim; Adaletli, İbrahim; Kayadibi, Yasemin; Emre, Şenol; Kılıç, Fahrettin; Dervişoğlu, Sergülen; Kuruğoğlu, Sebuh; Şenyüz, Osman Faruk

2014-01-01

Highlights: • We evaluated the impact of share wave elastography technique in differentiation hepatic hemangiomas from malignant liver tumors in pediatric population. • Share wave technique can increase the diagnostic capability of conventional ultrasonography in the differential diagnosis of liver tumors in children. • Share wave elastography is a potential adjunctive diagnostic technique for pediatric liver tumors. - Abstract: Objective: In children it is crucial to differentiate malignant liver tumors from the most common benign tumor, hepatic hemangiomas since the treatment strategies are quite different. We aimed to evaluate the efficiency of shear wave elastography (SWE) technique in differentiation of malignant hepatic tumors and hepatic hemangiomas. Methods: Twenty patients with hepatic tumor were included in our study. Two radiologists performed SWE for 13 patients with malignant hepatic tumors including hepatoblastoma (n = 7), hepatocellular carcinoma (n = 3), metastasis (n = 2), embryonal sarcoma (n = 1) and 7 patients with hepatic hemangioma. All of our patients were between the age of 1 and 192 months (mean age: 56.88 months). Receiver operating characteristic analysis was achieved to evaluate the diagnostic accuracy of SWE and to determine the optimal cut-off value in differentiation hepatic hemangioma from malignant hepatic tumors. Results: The mean SWE values (in kPa) for the first observer were 46.94 (13.8–145) and 22.38 (6.6–49.6) and those for the second observer were 57.91 (11–237) and 23.87 (6.4–57.5), respectively for malignant hepatic tumors and hepatic hemangiomas. The SWE values of malignant hepatic tumors were significantly higher than those of hepatic hemangioma (p = 0.02). The inter-observer agreement was almost perfect (0.81). The area under the receiver operating characteristic curve of SWE for differentiating the hepatic hemangioma from malignant hepatic tumors was 0.77 with a sensitivity of 72.7% and a specificity of 66

Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors.

Science.gov (United States)

Dondossola, Eleonora; Dobroff, Andrey S; Marchiò, Serena; Cardó-Vila, Marina; Hosoya, Hitomi; Libutti, Steven K; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2016-02-23

Circulating cancer cells can putatively colonize distant organs to form metastases or to reinfiltrate primary tumors themselves through a process termed "tumor self-seeding." Here we exploit this biological attribute to deliver tumor necrosis factor alpha (TNF), a potent antitumor cytokine, directly to primary and metastatic tumors in a mechanism that we have defined as "tumor self-targeting." For this purpose, we genetically engineered mouse mammary adenocarcinoma (TSA), melanoma (B16-F10), and Lewis lung carcinoma cells to produce and release murine TNF. In a series of intervention trials, systemic administration of TNF-expressing tumor cells was associated with reduced growth of both primary tumors and metastatic colonies in immunocompetent mice. We show that these malignant cells home to tumors, locally release TNF, damage neovascular endothelium, and induce massive cancer cell apoptosis. We also demonstrate that such tumor-cell-mediated delivery avoids or minimizes common side effects often associated with TNF-based therapy, such as acute inflammation and weight loss. Our study provides proof of concept that genetically modified circulating tumor cells may serve as targeted vectors to deliver anticancer agents. In a clinical context, this unique paradigm represents a personalized approach to be translated into applications potentially using patient-derived circulating tumor cells as self-targeted vectors for drug delivery.

CD40 dependent exacerbation of immune mediated hepatitis by hepatic CD11b+ Gr-1+ myeloid derived suppressor cells in tumor bearing mice

Science.gov (United States)

Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M.; Wiltrout, Robert H.; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A.; Manns, Michael P.; Wang, Ena; Marincola, Francesco M.; Korangy, Firouzeh; Greten, Tim F.

2015-01-01

Immunosuppressive CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) accumulate in the livers of tumor-bearing mice. We studied hepatic MDSC in two murine models of immune mediated hepatitis. Unexpectedly, treatment of tumor bearing mice with Concanavalin A or α-Galactosylceramide resulted in increased ALT and AST serum levels in comparison to tumor free mice. Adoptive transfer of hepatic MDSC into naïve mice exacerbated Concanavalin A induced liver damage. Hepatic CD11b+Gr-1+ cells revealed a polarized pro-inflammatory gene signature after Concanavalin A treatment. An interferon gamma- dependent up-regulation of CD40 on hepatic CD11b+Gr-1+ cells along with an up-regulation of CD80, CD86, and CD1d after Concanavalin A treatment was observed. Concanavalin A treatment resulted in a loss of suppressor function by tumor-induced CD11b+Gr-1+ MDSC as well as enhanced reactive oxygen species-mediated hepatotoxicity. CD40 knockdown in hepatic MDSC led to increased arginase activity upon Concanavalin A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40−/− tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased reactive oxygen species production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSC act as pro-inflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner. PMID:25616156

Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

International Nuclear Information System (INIS)

Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

2015-01-01

Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

Energy Technology Data Exchange (ETDEWEB)

Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

2015-08-14

Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

Tumor Cells Express FcγRl Which Contributes to Tumor Cell Growth and a Metastatic Phenotype

Directory of Open Access Journals (Sweden)

M. Bud Nelson

2001-01-01

Full Text Available High levels of circulating immune complexes containing tumor-associated antigens are associated with a poor prognosis for individuals with cancer. The ability of B cells, previously exposed to tumor-associated antigens, to promote both in vitro and in vivo tumor growth formed the rationale to evaluate the mechanism by which immune complexes may promote tumor growth. In elucidating this mechanism, FcγRl expression by tumor cells was characterized by flow cytometry, polymerase chain reaction, and sequence analysis. Immune complexes containing shed tumor antigen and anti-shed tumor antigen Ab cross-linked FcγRl-expressing tumor cells, which resulted in an induction of tumor cell proliferation and of shed tumor antigen production. Use of selective tyrosine kinase inhibitors demonstrated that tumor cell proliferation induced by immune complex cross-linking of FcγRl is dependent on the tyrosine kinase signal transduction pathway. A selective inhibitor of phosphatidylinositol-3 kinase also inhibited this induction of tumor cell proliferation. These findings support a role for immune complexes and FcγRl expression by tumor cells in augmentation of tumor growth and a metastatic phenotype.

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice

Directory of Open Access Journals (Sweden)

Liao Dezhong J

2008-01-01

Full Text Available Abstract Background Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Results Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT and liver metastatic lesions (LM compared to normal pancreas (NP. In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1 and Serine proteinase inhibitor A1 (Serpina1, and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. Conclusion We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.

Science.gov (United States)

Thakur, Archana; Bollig, Aliccia; Wu, Jiusheng; Liao, Dezhong J

2008-01-24

Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

Plasma circulating tumor DNA as an alternative to metastatic biopsies for mutational analysis in breast cancer.

Science.gov (United States)

Rothé, F; Laes, J-F; Lambrechts, D; Smeets, D; Vincent, D; Maetens, M; Fumagalli, D; Michiels, S; Drisis, S; Moerman, C; Detiffe, J-P; Larsimont, D; Awada, A; Piccart, M; Sotiriou, C; Ignatiadis, M

2014-10-01

Molecular screening programs use next-generation sequencing (NGS) of cancer gene panels to analyze metastatic biopsies. We interrogated whether plasma could be used as an alternative to metastatic biopsies. The Ion AmpliSeq™ Cancer Hotspot Panel v2 (Ion Torrent), covering 2800 COSMIC mutations from 50 cancer genes was used to analyze 69 tumor (primary/metastases) and 31 plasma samples from 17 metastatic breast cancer patients. The targeted coverage for tumor DNA was ×1000 and for plasma cell-free DNA ×25 000. Whole blood normal DNA was used to exclude germline variants. The Illumina technology was used to confirm observed mutations. Evaluable NGS results were obtained for 60 tumor and 31 plasma samples from 17 patients. When tumor samples were analyzed, 12 of 17 (71%, 95% confidence interval (CI) 44% to 90%) patients had ≥1 mutation (median 1 mutation per patient, range 0-2 mutations) in either p53, PIK3CA, PTEN, AKT1 or IDH2 gene. When plasma samples were analyzed, 12 of 17 (71%, 95% CI: 44-90%) patients had ≥1 mutation (median 1 mutation per patient, range 0-2 mutations) in either p53, PIK3CA, PTEN, AKT1, IDH2 and SMAD4. All mutations were confirmed. When we focused on tumor and plasma samples collected at the same time-point, we observed that, in four patients, no mutation was identified in either tumor or plasma; in nine patients, the same mutations was identified in tumor and plasma; in two patients, a mutation was identified in tumor but not in plasma; in two patients, a mutation was identified in plasma but not in tumor. Thus, in 13 of 17 (76%, 95% CI 50% to 93%) patients, tumor and plasma provided concordant results whereas in 4 of 17 (24%, 95% CI 7% to 50%) patients, the results were discordant, providing complementary information. Plasma can be prospectively tested as an alternative to metastatic biopsies in molecular screening programs. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology

Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury.

Science.gov (United States)

Jiao, Shu-Fan; Sun, Kai; Chen, Xiao-Jing; Zhao, Xue; Cai, Ning; Liu, Yan-Jun; Xu, Long-Mei; Kong, Xian-Ming; Wei, Li-Xin

2014-01-08

Patients with colorectal cancer (CRC) often develop liver metastases, in which case surgery is considered the only potentially curative treatment option. However, liver surgery is associated with a risk of ischemia-reperfusion (IR) injury, which is thought to promote the growth of colorectal liver metastases. The influence of IR-induced tumor necrosis factor alpha (TNF-α) elevation in the process still is unknown. To investigate the role of TNF-α in the growth of pre-existing micrometastases in the liver following IR, we used a mouse model of colorectal liver metastases. In this model, mice received IR treatment seven days after intrasplenic injections of colorectal CT26 cells. Prior to IR treatment, either TNF-α blocker Enbrel or low-dose TNF-α, which could inhibit IR-induced TNF-α elevation, was administered by intraperitoneal injection. Hepatic IR treatment significantly promoted CT26 tumor growth in the liver, but either Enbrel or low-dose TNF-α pretreatment reversed this trend. Further studies showed that the CT26 + IR group prominently increased the levels of ALT and AST, liver necrosis, inflammatory infiltration and the expressions of hepatic IL-6, MMP9 and E-selectin compared to those of CT26 group. Inhibition of TNF-α elevation remarkably attenuated the increases of these liver inflammatory damage indicators and tumor-promoting factors. These findings suggested that inhibition of TNF-α elevation delayed the IR-enhanced outgrowth of colorectal liver metastases by reducing IR-induced inflammatory damage and the formation of tumor-promoting microenvironments. Both Enbrel and low-dose TNF-α represented the potential therapeutic approaches for the protection of colorectal liver metastatic patients against IR injury-induced growth of liver micrometastases foci.

Thioredoxin induces Tregs to generate an immunotolerant tumor microenvironment in metastatic melanoma

Science.gov (United States)

Wang, Xiaogang; Dong, Haisheng; Li, Qi; Li, Yingxian; Hong, An

2015-01-01

Metastatic melanoma is a highly aggressive cancer that is very difficult to treat. Additionally, the antitumor immune reaction of melanoma is still unclear. Here we demonstrate an association between the expression and secretion of the antioxidant protein thioredoxin (TRX) and increasing tumor stage and metastasis in melanoma. To elucidate the role of TRX in melanoma, we assessed the correlation of TRX expression with different disease parameters in melanoma. We also examined the in vitro and in vivo effects of modulating TRX levels in melanoma cells using various methods of TRX depletion and augmentation. We further explored the effects of TRX on the cytokine milieu and the ability of TRX to regulate the proportion and specific activities of T-cell populations. We demonstrate that TRX expression correlates with Treg representation in clinical samples and, that modulation of TRX influences the induction of Tregs and the generation of an immunotolerant cytokine profile in mouse serum. Using a murine metastatic melanoma model, we identified a tumor immunoevasion mechanism whereby melanoma cell-secreted TRX enhances Treg infiltration. TRX displays chemotactic effects in recruiting Tregs, stimulates the conversion of conventional T cells to Tregs, and confers survival advantage to Tregs in the tumor microenvironment. In turn, this increase of Tregs generates immunotolerance in tissues and therefore decreases antitumor immune reactions. These results elucidate a mechanism by which TRX promotes metastatic melanoma in part through Treg recruitment to inhibit T-cell antitumor effects and suggest that TRX antibody may be useful in the clinic as a therapy against melanoma. PMID:26405597

Cannibalism: a way to feed on metastatic tumors.

Science.gov (United States)

Fais, Stefano

2007-12-18

Cannibalism of tumors is an old story for pathologists, but it remained a mystery for at least one century. Recent data highlighted tumor cannibalism as a key advantage in tumor malignancy, possibly involved in resistance of tumors to the specific immune reaction. However, new data suggests also that metastatic tumor cells may use this peculiar function to feed in conditions of low nutrient supply. This makes malignant cancer cells more similar to microorganisms, rather than to normal cells undergoing malignant transformation. In cytological or histological samples of human tumors it is common to detect cells with one or many vacuoles, possibly containing cells under degradation, that push the nucleus to the periphery giving it the shape of a crescent moon. The cannibal cells may feed on sibling tumor cells, but also of the lymphocytes that should kill them. Cannibal cells eat everything without distinguishing between the feeding materials, with a mechanism that mostly differ from typical phagocytosis. Despite such phenomenon is considered mainly non-selective, a molecular framework of factors that contribute to cannibalism has been described. This machinery includes the presence of an acidic environment that allows a continuous activation of specific lytic enzymes, such as cathepsin B. Cannibalism occurs in apparently well defined structures whose main actors are big caveolar-like vacuoles and a connection between caveolin-1 and the actin cytoskeleton through the actin-linker molecule ezrin. Each of the components of the cannibal framework may represent specific tumor targets for future new strategies against cancer.

Efficacy of percutaneous microwave coagulation therapy for nodular hepatic tumor : a preliminary study

Energy Technology Data Exchange (ETDEWEB)

Kim, Seon Hee; Bang, Sun Woo; Baek, Seung Il; Kim, Ho Kyun [Inje Univ. College of Medicine, Seoul (Korea, Republic of); Kim, Jeong Seok [Dongguk Univ. College of Medicine, Seoul (Korea, Republic of)

2001-04-01

Percutaneous microwave coagulation therapy (PMCT) uses a new energy source, microwave, in the treatment of solid neoplasms. We evaluated the efficacy of PMCT for nodular hepatic tumors in nine patients. Between December 1998 and June 1999, we performed PMCT in six patients with hepatocelluar carcinoma (HCC), two with one and three metastatic nodules each from colon cancer, and one with adenomatous hyperplasia. Four patients were female and five were male, and their age ranged between 44 and 71 (mean, 58.8) years. Under sonographic guidance a 14-gauge guiding needle was inserted percutaneously toward the lesion, and within it a needle electrode was precisely positioned. Microwave 2450MHz in frequency and with 60 or 80-watt emission was generated for 80{approx}90 seconds. We evaluated the ultrasound findings obtained during the procedure, pre-PMCT and follow-up CT images, changes in tumor marker(AFP or CA19-9) levels and the results of liver function tests, and complications arising during the six-month period following PMCT. Immediately after microwave emission, characteristic hyperechogenicity appeared on the real-time sonogram. Two patients with HCC underwent CT before PMCT, and typical enhancement during the arterial phase and washout during the portovenous phase was observed. In one patient, two metastatic lesions from colon cancer showed delayed enhancement on pre-PMCT CT. Initial follow-up CT, performed between I and 4 weeks after the PMCT procedure, showed that eight lesions-including two HCCs which were highly enhanced on CT before PMCT-showed no contrast enhancement, and three others showed delayed enhancement. Two of the eight lesions which showed no contrast enhancement at initial follow-up CT were markedly decreased in size (from 2.9 and 4.0 cm to 1.0 and 2.0 cm, respectively) at subsequent follow-up 3 months and 6 months later, respectively. One of the three lesions showing delayed enhancement had increased in size from 4.1 to 5.5 cm at subsequent

Nanoroughened adhesion-based capture of circulating tumor cells with heterogeneous expression and metastatic characteristics

International Nuclear Information System (INIS)

Chen, Weiqiang; Allen, Steven G.; Reka, Ajaya Kumar; Qian, Weiyi; Han, Shuo; Zhao, Jianing; Bao, Liwei; Keshamouni, Venkateshwar G.; Merajver, Sofia D.; Fu, Jianping

2016-01-01

Circulating tumor cells (CTCs) have shown prognostic relevance in many cancer types. However, the majority of current CTC capture methods rely on positive selection techniques that require a priori knowledge about the surface protein expression of disseminated CTCs, which are known to be a dynamic population. We developed a microfluidic CTC capture chip that incorporated a nanoroughened glass substrate for capturing CTCs from blood samples. Our CTC capture chip utilized the differential adhesion preference of cancer cells to nanoroughened etched glass surfaces as compared to normal blood cells and thus did not depend on the physical size or surface protein expression of CTCs. The microfluidic CTC capture chip was able to achieve a superior capture yield for both epithelial cell adhesion molecule positive (EpCAM+) and EpCAM- cancer cells in blood samples. Additionally, the microfluidic CTC chip captured CTCs undergoing transforming growth factor beta-induced epithelial-to-mesenchymal transition (TGF-β-induced EMT) with dynamically down-regulated EpCAM expression. In a mouse model of human breast cancer using EpCAM positive and negative cell lines, the number of CTCs captured correlated positively with the size of the primary tumor and was independent of their EpCAM expression. Furthermore, in a syngeneic mouse model of lung cancer using cell lines with differential metastasis capability, CTCs were captured from all mice with detectable primary tumors independent of the cell lines’ metastatic ability. The microfluidic CTC capture chip using a novel nanoroughened glass substrate is broadly applicable to capturing heterogeneous CTC populations of clinical interest independent of their surface marker expression and metastatic propensity. We were able to capture CTCs from a non-metastatic lung cancer model, demonstrating the potential of the chip to collect the entirety of CTC populations including subgroups of distinct biological and phenotypical properties. Further

High contrast enhancement aspect of dynamic computed tomography with arterial infusion - DCT-AI. Its clinical applications on hepatic tumors and basic experiments

Energy Technology Data Exchange (ETDEWEB)

Kato, Seishi; Iwasaki, Naoya; Matsumura, Yoshimitsu; Kuramae, Shigeru; Mishiro, Tadashi

1983-06-01

Dynamic computed tomography was performed on 112 cases possibly having hepatic tumors with intraarterial infusion of undiluted contrast into a selectively placed catheter following angiographies. Our dynamic program could evaluate not only early phase of enhancement but also late phase up to 120 sec. Reconstructed views from early scans and magnified views were very useful to evaluate minute sequential changes. Hepatic masses less than 5 cm in size were found in thirty-one cases. Patterns of tumor enhancement and time-density curves have been analysed to correlate them with histology. Four types of tumor enhancement were noted: (1) homogeneous (2) patchy (3) mottled (4) ringed. Characteristic changes were observed in hepatocellular carcinoma - HCC - (mostly mottled) and haemangioma (mostly patchy). The former was divided in two groups reflecting the cellular maturity. The metastatic tumor could be enhanced in a ringed form with dendritic pattern of supplying vascularities in some cases. To support the use of undiluted contrast and to investigate the diagnostic efficacy of high contrast enhancement, experiments were performed by taking transaxial views of an acrylic phantom immersed in different concentrations of contrast. Analysis of CT images taken at different HU values ranging from 0 to 450 demonstrated that the higher the concentration of contrast, the better the spatial resolution was. Also larger magnification could be expected by using higher concentration of contrast. Although our Dynamic Computed Tomography with Arterial Infusion of Contrast still has drawbacks and limited indications, we advocate it as a better way of enhancement to detect and evaluate the hepatic masses, which sometimes elude the examiner's grasp with conventional way of enhancement. (author).

Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castrationresistant prostate cancer: a report from the PETRUS prospective study

Science.gov (United States)

Massard, Christophe; Oulhen, Marianne; Le Moulec, Sylvestre; Auger, Nathalie; Foulon, Stéphanie; Abou-Lovergne, Aurélie; Billiot, Fanny; Valent, Alexander; Marty, Virginie; Loriot, Yohann; Fizazi, Karim; Vielh, Philippe; Farace, Francoise

2016-01-01

Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR-amplification was detected in CellSearch-captured CTCs, but not in ISET-enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET-enriched CTCs indicating a higher heterogeneity in CTCs. Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET-filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients. PMID:27391263

Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report.

Science.gov (United States)

Yoshino, Kenji; Manaka, Dai; Kudo, Ryo; Kanai, Shunpei; Mitsuoka, Eisei; Kanto, Satoshi; Hamasu, Shinya; Konishi, Sayuri; Nishitai, Ryuta

2017-08-18

Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years. A 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression. To the

An Unusual Case of Hepatic Tumor in an Elderly Patient

Directory of Open Access Journals (Sweden)

Huan-Lin Chen

2009-09-01

Full Text Available Malignant epithelioid hemangioendothelioma is a rare hepatic tumor of vascular origin. It is most commonly found in young to middle-aged women, and the tumors vary in their reported potential for malignancy. The etiologic factors are not yet clear, and some investigators have suggested an association with oral contraceptives, whereas others have noted an association with exposure to vinyl chloride, asbestos, thorotrast, major trauma to the liver, viral hepatitis, primary biliary cirrhosis, and alcohol consumption. The clinical manifestations are nonspecific, and most are asymptomatic. Among symptomatic patients, the most common symptom is right upper quadrant pain, followed by jaundice, weight loss, fatigue, ascites, hepatomegaly, and fever. The only definitive diagnosis requires immunohistochemical evidence of endothelial differentiation, which is demonstrated by the presence of factor VIII-related antigen and cytokeratins. As with most mesenchymal tumors, surgical resection is the most effective means of controlling local disease and preventing distant metastasis, although adjuvant therapies have been offered for patients with unresectable tumors or who are not transplant candidates. We present the case of an elderly man with a hepatic malignant epithelioid hemangioendothelioma, and we reviewed the English-language literature.

The Impact of Laparoscopic Approaches on Short-term Outcomes in Patients Undergoing Liver Surgery for Metastatic Tumors.

Science.gov (United States)

Karagkounis, Georgios; Seicean, Andreea; Berber, Eren

2015-06-01

To compare the perioperative outcomes associated with open and laparoscopic (LAP) surgical approaches for liver metastases. The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all adult patients who underwent surgical therapy for metastatic liver tumors between 2006 and 2012 (N=7684). Patients who underwent >1 procedure were excluded. Logistic regression after matching on propensity scores was used to assess the association between surgical approaches and perioperative outcomes. A total of 4555 patients underwent open resection, 387 LAP resection, 297 open radiofrequency ablation (RFA), and 265 LAP RFA. In propensity-matched samples (over 95% of patients successfully matched), there was no significant difference between LAP resection and LAP RFA in perioperative complications and length of stay and both compared favorably with their open counterparts. Minimally invasive approaches for secondary hepatic malignancies were associated with improved postoperative morbidity and length of stay and should be preferred in appropriate patients.

Hepatic Radiofrequency Ablation–induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition

Science.gov (United States)

Kumar, Gaurav; Moussa, Marwan; Wang, Yuanguo; Rozenblum, Nir; Galun, Eithan; Goldberg, S. Nahum

2016-01-01

Purpose To elucidate how hepatic radiofrequency (RF) ablation affects distant extrahepatic tumor growth by means of two key molecular pathways. Materials and Methods Rats were used in this institutional animal care and use committee–approved study. First, the effect of hepatic RF ablation on distant subcutaneous in situ R3230 and MATBIII breast tumors was evaluated. Animals were randomly assigned to standardized RF ablation, sham procedure, or no treatment. Tumor growth rate was measured for 3½ to 7 days. Then, tissue was harvested for Ki-67 proliferative indexes and CD34 microvascular density. Second, hepatic RF ablation was performed for hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and c-Met receptor expression measurement in periablational rim, serum, and distant tumor 24 hours to 7 days after ablation. Third, hepatic RF ablation was combined with either a c-Met inhibitor (PHA-665752) or VEGF receptor inhibitor (semaxanib) and compared with sham or drug alone arms to assess distant tumor growth and growth factor levels. Finally, hepatic RF ablation was performed in rats with c-Met–negative R3230 tumors for comparison with the native c-Met–positive line. Tumor size and immunohistochemical quantification at day 0 and at sacrifice were compared with analysis of variance and the two-tailed Student t test. Tumor growth curves before and after treatment were analyzed with linear regression analysis to determine mean slopes of pre- and posttreatment growth curves on a per-tumor basis and were compared with analysis of variance and paired two-tailed t tests. Results After RF ablation of normal liver, distant R3230 tumors were substantially larger at 7 days compared with tumors treated with the sham procedure and untreated tumors, with higher growth rates and tumor cell proliferation. Similar findings were observed in MATBIII tumors. Hepatic RF ablation predominantly increased periablational and serum HGF and downstream distant tumor

Assessment of Tumor Radioresponsiveness and Metastatic Potential by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

International Nuclear Information System (INIS)

Ovrebo, Kirsti Marie; Gulliksrud, Kristine; Mathiesen, Berit; Rofstad, Einar K.

2011-01-01

Purpose: It has been suggested that gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may provide clinically useful biomarkers for personalized cancer treatment. In this preclinical study, we investigated the potential of DCE-MRI as a noninvasive method for assessing the radioresponsiveness and metastatic potential of tumors. Methods and Materials: R-18 melanoma xenografts growing in BALB/c nu/nu mice were used as experimental tumor models. Fifty tumors were subjected to DCE-MRI, and parametric images of K trans (the volume transfer constant of Gd-DTPA) and v e (the fractional distribution volume of Gd-DTPA) were produced by pharmacokinetic analysis of the DCE-MRI series. The tumors were irradiated after the DCE-MRI, either with a single dose of 10 Gy for detection of radiobiological hypoxia (30 tumors) or with five fractions of 4 Gy in 48 h for assessment of radioresponsiveness (20 tumors). The host mice were then euthanized and examined for lymph node metastases, and the primary tumors were resected for measurement of cell survival in vitro. Results: Tumors with hypoxic cells showed significantly lower K trans values than tumors without significant hypoxia (p trans decreased with increasing cell surviving fraction for tumors given fractionated radiation treatment (p trans values than tumors in metastasis-negative mice (p e and tumor hypoxia, radioresponsiveness, or metastatic potential could not be detected. Conclusions: R-18 tumors with low K trans values are likely to be resistant to radiation treatment and have a high probability of developing lymph node metastases. The general validity of these observations should be investigated further by studying preclinical tumor models with biological properties different from those of the R-18 tumors.

Utility and limitation of radiosurgery for metastatic brain tumors

International Nuclear Information System (INIS)

Kagawa, Kota; Kiya, Katsuzo; Satoh, Hideki; Mizoue, Tatsuya; Matsushige, Toshinori; Araki, Hayato; Akimitsu, Tomohide

2003-01-01

The purpose of this study was to evaluate the utility and limitations of radiosurgery for metastatic brain lesions, and to compare the clinical results of stereotactic radiosurgery (SRS) with those of whole-brain radiation therapy (WBRT) in 45 patients with metastatic brain tumors. The patients were divided into two groups: the SRS group (22 patients) and the WBRT group (23 patients). Mean survival was not significantly different between the two groups. However, in patients with 6 or more lesions, both survival time and recurrence-free time in the SRS group were inferior to those in the WBRT group. The main complication in the SRS group was perifocal edema, while dementia was seen in the WBRT group. The bedridden period was longer in the WBRT group than in the SRS group. Death caused by brain lesions was rare in both groups. From these results, SRS preserves high quality of life longer than WBRT, but SRS should be cautiously used in patients with 6 or more lesions. (author)

Hepatic VX2 tumor after portal vein occlusion in rabbits: evaluation with DSA

International Nuclear Information System (INIS)

Qi Yueyong; Zou Liguang; Dai Shuhua; Zhang Qichuan; Chen Lin; Huang Xiaobing; Huan Guangqiang

2006-01-01

Objective: To study the value of DSA for hepatic vascular anatomy, and to evaluate the efficacy of portal vein occlusion in rabbits with hepatic VX2 tumor. Methods: Twenty New Zealand white rabbits were randomly divided into two groups with 10 in each group, including test group A and positive control group B of ham operation. For the test group A, portal branch ligation (PBL) was performed for the left external branch after 3 weeks of the tumor implantation to the left external lobe. Two weeks later, the DSA of hepatic artery and portal vein were performed in all of the rabbits. Results: The total displaying effectiveness of the branches of hepatic artery by DSA was better than that by vascular perfusion. There was hypovascular blood supply to hepatic artery implantation of the tumor in the test group A, comparing with that of the group B. Conclusion: DSA can clearly display special details of the hepatic vascular anatomy in rabbits, and play an important role in post-procedural evaluation of the portal vein occlusion in rabbits. (authors)

Determinants of survival after liver resection for metastatic colorectal carcinoma.

Science.gov (United States)

Parau, Angela; Todor, Nicolae; Vlad, Liviu

2015-01-01

Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate

Rare incidence of tumor lysis syndrome in metastatic prostate cancer following treatment with docetaxel.

Science.gov (United States)

Bhardwaj, Sharonlin; Varma, Seema

2018-03-01

Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors. In this report, the authors describe a specific case of tumor lysis syndrome in a patient with metastatic prostate cancer following treatment with docetaxel.

Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients Undergoing Surgery for Metastatic Brain Tumors.

Science.gov (United States)

Wu, Adela; Weingart, Jon D; Gallia, Gary L; Lim, Michael; Brem, Henry; Bettegowda, Chetan; Chaichana, Kaisorn L

2017-08-01

Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined. Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively. Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases. The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Tumor-reactive immune cells protect against metastatic tumor and induce immunoediting of indolent but not quiescent tumor cells.

Science.gov (United States)

Payne, Kyle K; Keim, Rebecca C; Graham, Laura; Idowu, Michael O; Wan, Wen; Wang, Xiang-Yang; Toor, Amir A; Bear, Harry D; Manjili, Masoud H

2016-09-01

Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25(+) NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25(+) NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor cells. Adoptive immunotherapy also induced tumor immunoediting, resulting in tumor escape and associated disease-related mortality. To identify a tumor target that is incapable of escape from the immune response, we used dormant tumor cells. We used Adriamycin chemotherapy or radiation therapy, which simultaneously induce tumor cell death and tumor dormancy. Resultant dormant cells became refractory to additional doses of Adriamycin or radiation therapy, but they remained sensitive to tumor-reactive immune cells. Importantly, we discovered that dormant tumor cells contained indolent cells that expressed low levels of Ki67 and quiescent cells that were Ki67 negative. Whereas the former were prone to tumor immunoediting and escape, the latter did not demonstrate immunoediting. Our results suggest that immunotherapy could be highly effective against quiescent dormant tumor cells. The challenge is to develop combinatorial therapies that could establish a quiescent type of tumor dormancy, which would be the best target for immunotherapy. © The Author(s).

Increased metastatic potential of tumor cells in von Willebrand factor-deficient mice.

Science.gov (United States)

Terraube, V; Pendu, R; Baruch, D; Gebbink, M F B G; Meyer, D; Lenting, P J; Denis, C V

2006-03-01

The key role played by von Willebrand factor (VWF) in platelet adhesion suggests a potential implication in various pathologies, where this process is involved. In cancer metastasis development, tumor cells interact with platelets and the vessel wall to extravasate from the circulation. As a potential mediator of platelet-tumor cell interactions, VWF could influence this early step of tumor spread and therefore play a role in cancer metastasis. To investigate whether VWF is involved in metastasis development. In a first step, we characterized the interaction between murine melanoma cells B16-BL6 and VWF in vitro. In a second step, an experimental metastasis model was used to compare the formation of pulmonary metastatic foci in C57BL/6 wild-type and VWF-null mice following the injection of B16-BL6 cells or Lewis lung carcinoma cells. In vitro adhesion assays revealed that VWF is able to promote a dose-dependent adhesion of B16-BL6 cells via its Arg-Gly-Asp (RGD) sequence. In the experimental metastasis model, we found a significant increase in the number of pulmonary metastatic foci in VWF-null mice compared with the wild-type mice, a phenotype that could be corrected by restoring VWF plasma levels. We also showed that increased survival of the tumor cells in the lungs during the first 24 h in the absence of VWF was the cause of this increased metastasis. These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated.

Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castration-resistant prostate cancer: A report from the PETRUS prospective study.

Science.gov (United States)

Massard, Christophe; Oulhen, Marianne; Le Moulec, Sylvestre; Auger, Nathalie; Foulon, Stéphanie; Abou-Lovergne, Aurélie; Billiot, Fanny; Valent, Alexander; Marty, Virginie; Loriot, Yohann; Fizazi, Karim; Vielh, Philippe; Farace, Francoise

2016-08-23

Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR-amplification was detected in CellSearch-captured CTCs, but not in ISET-enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET-enriched CTCs indicating a higher heterogeneity in CTCs.Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET-filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients.

IFNα gene/cell therapy curbs colorectal cancer colonization of the liver by acting on the hepatic microenvironment.

Science.gov (United States)

Catarinella, Mario; Monestiroli, Andrea; Escobar, Giulia; Fiocchi, Amleto; Tran, Ngoc Lan; Aiolfi, Roberto; Marra, Paolo; Esposito, Antonio; Cipriani, Federica; Aldrighetti, Luca; Iannacone, Matteo; Naldini, Luigi; Guidotti, Luca G; Sitia, Giovanni

2016-02-01

Colorectal cancer (CRC) metastatic dissemination to the liver is one of the most life-threatening malignancies in humans and represents the leading cause of CRC-related mortality. Herein, we adopted a gene transfer strategy into mouse hematopoietic stem/progenitor cells to generate immune-competent mice in which TEMs-a subset of Tie2(+) monocytes/macrophages found at peritumoral sites-express interferon-alpha (IFNα), a pleiotropic cytokine with anti-tumor effects. Utilizing this strategy in mouse models of CRC liver metastasis, we show that TEMs accumulate in the proximity of hepatic metastatic areas and that TEM-mediated delivery of IFNα inhibits tumor growth when administered prior to metastasis challenge as well as on established hepatic lesions, improving overall survival. Further analyses unveiled that local delivery of IFNα does not inhibit homing but limits the early phases of hepatic CRC cell expansion by acting on the radio-resistant hepatic microenvironment. TEM-mediated IFNα expression was not associated with systemic side effects, hematopoietic toxicity, or inability to respond to a virus challenge. Along with the notion that TEMs were detected in the proximity of CRC metastases in human livers, these results raise the possibility to employ similar gene/cell therapies as tumor site-specific drug-delivery strategies in patients with CRC. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Therapy of metastatic pancreatic neuroendocrine tumors (pNETs). Recent insights and advances

International Nuclear Information System (INIS)

Ito, Tetsuhide; Igarashi, Hisato; Jensen, R.T.

2012-01-01

Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. (author)

Experimental ex-vivo validation of PMMA-based bone cements loaded with magnetic nanoparticles enabling hyperthermia of metastatic bone tumors

Directory of Open Access Journals (Sweden)

Mariem Harabech

2017-05-01

Full Text Available Percutaneous vertebroplasty comprises the injection of Polymethylmethacrylate (PMMA bone cement into vertebrae and can be used for the treatment of compression fractures of vertebrae. Metastatic bone tumors can cause such compression fractures but are not treated when injecting PMMA-based bone cement. Hyperthermia of tumors can on the other hand be attained by placing magnetic nanoparticles (MNPs in an alternating magnetic field (AMF. Loading the PMMA-based bone cement with MNPs could both serve vertebra stabilization and metastatic bone tumor hyperthermia when subjecting this PMMA-MNP to an AMF. A dedicated pancake coil is designed with a self-inductance of 10 μH in series with a capacitance of 0.1 μF that acts as resonant inductor-capacitor circuit to generate the AMF. The thermal rise is appraised in beef vertebra placed at 10 cm from the AMF generating circuit using optical temperatures sensors, i.e. in the center of the PMMA-MNP bone cement, which is located in the vicinity of metastatic bone tumors in clinical applications; and in the spine, which needs to be safeguarded to high temperature exposures. Results show a temperature rise of about 7 °C in PMMA-MNP whereas the temperature rise in the spine remains limited to 1 °C. Moreover, multicycles heating of PMMA-MNP is experimentally verified, validating the technical feasibility of having PMMA-MNP as basic component for percutaneous vertebroplasty combined with hyperthermia treatment of metastatic bone tumors.

The effect of TACE with endostatin on hemodynamics in hepatic implantation tumor using Doppler ultrasonography

International Nuclear Information System (INIS)

Zhou Guangli; Wu Yuanyuan; Wang Bin; Liu Yan; Zheng Chuanli; Sang Li; Liu Feng

2009-01-01

Objective: To investigate the hemodynamic changes in the rabbit liver and VX2 hepatic implantation tumor after treatment by transcatheter arterial chemoembolization (TACE)/endostatin using Doppler ultrasonography. Methods: Twenty rabbits with VX2 hepatic tumor were randomly distributed into the control group (n=10) and the anti- angiogenesis group (n=10). The rabbits were administered with endostatin and adriamycin-lipiodol in the anti-angiogenesis group and with 37℃ saline in the control group via hepatic artery. The hemodynamic changes of the tumors, hepatic artery, and portal vein were recorded with Doppler ultrasonography 1 week after the treatment. The results before and after the treatment were compared. Results: In the control group, the maximal hepatic artery blood flow velocity was significantly higher than that before the treatment (P<0.05). However, the resistance index and the portal vein blood flow velocities had no significantly change compared with those before the treatment (P>0.05). In the anti-angiogenesis group, the hepatic artery blood flow velocity was significantly lower than that before the treatment (P<0.05), and the resistance index was increased (P<0.05). However, the portal vein blood flow velocity had no significantly change (P>0.05). The blood flow signal in all tumors was rich before embolization. After TACE, the blood flow signal was significantly decreased, even partly disappeared in the anti-angiogenesis group. Conclusion: TACE with endostatin can effectively block the blood supplement of VX2 hepatic implantation tumor. Doppler ultrasonography can detected the blood flow changes and can be used in evaluating the therapeutic effect in hepatic implantation tumor. (authors)

Quality of Life in Patients With Primary and Metastatic Brain Tumors in the Literature as Assessed by the FACT-Br.

Science.gov (United States)

Chiu, Nicholas; Chiu, Leonard; Zeng, Liang; Zhang, Liying; Cella, David; Popovic, Marko; Chow, Ronald; Lam, Henry; Poon, Michael; Chow, Edward

2012-12-01

The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a quality of life (QOL) assessment tool that was originally developed for use in patients with primary brain tumors. However, the tool has also been used to assess QOL in patients with metastatic brain tumors. The purpose of this study is to compare the differences in QOL responses as assessed by the FACT-Br in patients with primary and metastatic brain neoplasms. A systematic literature search was conducted using the OvidSP platform in MEDLINE (1946 to July Week 2 2012) and EMBASE (1980 to 2012 Week 28). Articles in which the FACT-Br was used as a QOL assessment for patients with malignant brain tumors (both primary and metastatic) were included in the study. The weighted means of FACT-Br subscale and overall scores were calculated for the studies. To compare these scores, weighted analysis of variance was conducted and PROC GLM was performed for the data. A P-value of Br for assessment of QOL were identified. Social and functional well-being were significantly better in patients with primary brain tumors (weighted mean score of 22.2 vs. 10.7, P = 0.0026, 16.9 vs. 6.2, P = 0.0025, respectively). No other scale of the FACT-Br was significantly different between the two groups and the performance status of patients included in both groups was similar. Patients with primary brain cancer seemed to have better social and functional well-being scores than those with metastatic brain tumors. Other QOL domains were similar between these two groups. However, the heterogeneity in the included studies and the low sample size of included samples in patients with metastatic brain tumors could have confounded our findings.

Hyperdensity liver tumor on plain CT

Energy Technology Data Exchange (ETDEWEB)

Hirota, Shozo; Hanaguri, Katsuro [Kochi Municipal Central Hospital (Japan); Shimizu, Masahumi; Sako, Masao; Harada, Yasushi

1984-12-01

Most liver tumors on plain CT have been recognized as low density or iso-density masses. Sometimes calcified high density masses were shown on plain CT in case of cysts or metastatic liver tumors. However, hyperdensity mass of the liver on CT, of which the density was a little higher than surrounding tissues, was very rare. Recently 7 patients with hyperdensity liver masses on plain CT were experienced: 6 hepatocellular carcinomas and 1 hepatic cavernous hemangioma. A single hyperdensity mass was shown in 4 patients, a hyperdensity mass of multiple hepatic tumors was shown in 2 patients, and some hyperdensity masses of multiple hepatic tumors were shown in 1 patient. Lesions are classified in 3 types according to the appearance of hyperdensity masses: diffuse hyperdensity all over the mass, ring like hyperdensity, creascent like hyperdensity. Intravenous contrast enhancement was performed in 2 patients: one with a primary hepatocellular carcinoma, and another with a hepatic cavernous hemangioma. In the former case the tumor margin had changed unclear, in the latter case the tumor was markedly enhanced. Our results revealed that hyperdensity liver tumors were divided into 2 types: One type, shown in a cavernous hemangioma with fatty liver, demonstrated relative hyperdensity due to lower density of the surrounding tissue. Another type, shown in 6 hepatocellular carcinomas, showed hyperdensity since the density of the tumor was hyperdensity relative to the surrounding tissue of the liver. It was suggested that the tumor with the latter type had been strongly probable of malignant one, and been recommended to receive further examination. Cause of hyperdensity was thought to be due to hemorrhage, though microcalcification could not be denyed. In Japan, no hyperdensity liver tumor had been reported partly due to a wide window width with which CT photographs were taken.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

Science.gov (United States)

Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

1998-01-01

The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

Accessory hepatic lobe simulating a left hemidiaphragmatic tumor

International Nuclear Information System (INIS)

Kuroiwa, Toshiro; Hirata, Hitoshi; Iwashita, Akinori; Yasumori, Kotaro; Mogami, Hiroshi; Teraoka, Hiroaki

1984-01-01

A 72-year-old woman with a 20-year history of neuralgia was confirmed at surgery to have a tumor in the left hemidiaphragmatic region which was connected with the left lobe of the liver. Reassessment of radiological diagnosis after surgery revealed that hepatobiliary scintigraphy and computed tomography using left anterior oblique scanning are useful in differentiating the accessory hepatic lobe of the liver from a tumor and in confirming the diagnosis, respectively. (Namekawa, K.)

Floating tumor debris. A cause of intermittent biliary obstruction.

Science.gov (United States)

Roslyn, J J; Kuchenbecker, S; Longmire, W P; Tompkins, R K

1984-11-01

Tumor debris, free-floating in the major biliary ductal system, is a cause of intermittent biliary obstruction that has previously not been recognized. Six patients had hepatic neoplasms with episodic jaundice and/or cholangitis due to floating tumor debris. Diagnosis included metastatic adenocarcinoma of the colon (n = 3), cholangiocarcinoma (n = 1), hepatocellular carcinoma (n = 1), and cavernous hemangioma (n = 1). All patients underwent biliary exploration, with hepatic resection and transhepatic intubation in two and T-tube placement in four. One patient died in the early postoperative period, and the major complication rate in the five survivors was 0%. Four of the five survivors had no further episodes suggestive of major bile duct obstruction. Our experience emphasizes the importance of distinguishing extrahepatic obstruction secondary to tumor debris from the more common causes of jaundice in patients with tumors and suggests that safe and effective palliation can be achieved in these patients.

[A Case of an Abdominal Desmoplastic Small Round Cell Tumor with Metastasis in the Medulla Oblongata].

Science.gov (United States)

Azami, Ayaka; Takano, Yoshinao; Honda, Michitaka; Todate, Yukitoshi; Tada, Takeshi; Waragai, Mitsuru; Fukushima, Daizo; Suzuki, Nobuyasu; Sato, Atai; Abe, Tsuyoshi; Teranishi, Yasushi; Sakuma, Hideo

2016-11-01

A desmoplastic small round cell tumor(DSRCT)is a very rare malignant tumor that mainly occurs in the intra-abdominal cavity in young adults.This neoplasm has an extremely poor prognosis, with a clinical course characterized by rapid progression and metastasis.We present a 31-year-old man who presented with chief complaints of dysphagia, ataxic gait, and hoarseness.He first underwent surgical resection of a tumor in the medulla oblongata; however, the lesion was suspected to be a metastatic neoplasm.Following a thorough medical examination, the patient was diagnosed with retroperitoneal DSRCT with multiple metastatic lesions.He received multidisciplinary treatment including debulking surgery for the primary lesion; radiotherapy for metastatic lesions in the brain, abdomen, and cervical lymph nodes; hepatic artery embolization for liver metastasis; and systemic chemotherapy.The patient died of progressive disease 17 months after the initial diagnosis.

RT-06GAMMA KNIFE SURGERY AFTER NAVIGATION-GUIDED ASPIRATION FOR CYSTIC METASTATIC BRAIN TUMORS

Science.gov (United States)

Chiba, Yasuyoshi; Mori, Kanji; Toyota, Shingo; Kumagai, Tetsuya; Yamamoto, Shota; Sugano, Hirofumi; Taki, Takuyu

2014-01-01

Metastatic brain tumors over 3 cm in diameter (volume of 14.1ml) are generally considered poor candidates for Gamma Knife surgery (GKS). We retrospectively assessed the method and efficacy of GKS for large cystic metastatic brain tumors after navigation-guided aspiration under local anesthesia. From September 2007 to April 2014, 38 cystic metastatic brain tumors in 32 patients (12 males, 20 females; mean age, 63.2 years) were treated at Kansai Rosai Hospital. The patients were performed navigation-guided cyst aspiration under local anesthesia, then at the day or the next day, were performed GKS and usually discharged on the day. The methods for preventing of leptomeningeal dissemination are following: 1) puncture from the place whose cerebral thickness is 1 cm or more; 2) avoidance of Ommaya reservoir implantation; and 3) placement of absorbable gelatin sponge to the tap tract. Tumor volume, including the cystic component, decreased from 25.4 ml (range 8.7-84.7 ml) to 11.4 ml (range 2.9-36.7 ml) following aspiration; the volume reduction was approximately 51.6%. Follow-up periods in the study population ranged from 0 to 24 months (median 3.5 months). The overall median survival was 6.7 months. There was no leptomeningeal dissemination related to the aspiration. One patient experienced radiation necrosis after GKS, one patient experienced re-aspiration by failure of aspiration, and two patients experienced surgical resections and one patient experienced re-aspiration by cyst regrowth after GKS. Long-term hospitalization is not desirable for the patients with brain metastases. In japan, Long-term hospitalization is required for surgical resection or whole brain radiation therapy, but only two days hospitalization is required for GKS after navigation-guided aspiration at our hospital. This GKS after navigation-guided aspiration is more effective and less invasive than surgical resection or whole brain radiation therapy.

Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer

NARCIS (Netherlands)

Cohen, Steven J.; Punt, Cornelis J. A.; Iannotti, Nicholas; Saidman, Bruce H.; Sabbath, Kert D.; Gabrail, Nashat Y.; Picus, Joel; Morse, Michael; Mitchell, Edith; Miller, M. Craig; Doyle, Gerald V.; Tissing, Henk; Terstappen, Leon W. M. M.; Meropol, Neal J.

2008-01-01

As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC. In a prospective multicenter study, CTCs

Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

Science.gov (United States)

Lambrescu, Ioana Maria; Martin, Sorina; Cima, Luminita; Herlea, Vlad; Badiu, Corin; Fica, Simona

2015-06-01

A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.

Diffuse Hepatic Epithelioid Hemangioendothelioma Developed in a Patient with Hepatitis C Cirrhosis

Directory of Open Access Journals (Sweden)

Pedro W. Baron

2014-01-01

Full Text Available Hepatic epithelioid hemangioendothelioma (HEHE is an infrequent vascular tumor of endothelial origin that primarily occurs in women in the mid-fifth decade of life without underlying chronic liver disease or cirrhosis. Liver transplant should be the first-line of therapy in patients with large or diffuse unresectable tumors even in the presence of metastatic disease due to the favorable long-term outcome. We report the case of a 48-year-old female who complained of abdominal pain and weight loss. She has a history of cirrhosis secondary to chronic hepatitis C (HCV and was treated with interferon and ribavirin with sustained virological response. Her work-up revealed multiple confluent infiltrating bilobar liver masses diagnosed as HEHE. She underwent a successful liver transplant without evidence of recurrent HCV infection. She developed cervical spine (C4-C6 HEHE metastases 4 years after transplant. She underwent surgical resection and local radiotherapy after resection with good clinical response. To the best of our knowledge, this is the first report of HEHE that developed in a patient with HCV cirrhosis successfully treated with antiviral therapy before transplant and liver transplant with good allograft function without evidence of recurrent liver tumor or HCV infection but developed metastases to the cervical spine 4 years after transplant.

F-18 FDG PET/CT imaging of primary hepatic neuroendocrine tumor

Directory of Open Access Journals (Sweden)

Katsuya Mitamura

2015-01-01

Full Text Available Primary hepatic neuroendocrine tumors (PHNETs are extremely rare neoplasms. Herein, we report a case of a 70-year-old man with a hepatic mass. The non-contrast computed tomography (CT image showed a low-density mass, and dynamic CT images indicated the enhancement of the mass in the arterial phase and early washout in the late phase. F18- fluorodeoxyglucose (18F-FDG positron emission tomography (PET and fused PET/CT images showed increased uptake in the hepatic mass. Whole-body 18F-FDG PET images showed no abnormal activity except for the liver lesion. Presence of an extrahepatic tumor was also ruled out by performing upper gastrointestinal endoscopy, total colonoscopy, and chest and abdominal CT. A posterior segmentectomy was performed, and histologic examination confirmed a neuroendocrine tumor (grade 1. The patient was followed up for about 2 years after the resection, and no extrahepatic lesions were radiologically found. Therefore, the patient was diagnosed with PHNET. To the best of our knowledge, no previous case of PHNET have been detected by 18F-FDG PET imaging.

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

Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy

Directory of Open Access Journals (Sweden)

Paola Ulivi

2017-06-01

Full Text Available There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided in patients with metastatic colorectal cancer (mCRC. We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter “Italian Trial in Advanced Colorectal Cancer (ITACa”, randomized to receive first-line chemotherapy (CT or CT plus bevacizumab (CT + B. RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF, endothelial nitric oxide synthase (eNOS, cyclooxygenase-2 (COX2, ephrin type-B receptor 4 (EPHB4, hypoxia-inducible factor 1-alpha (HIF-1α, lactate dehydrogenase (LDH, and high-sensitivity C reactive protein (hs-CRP; and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017. Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.

A new technique for labeling of Lipiodol with 188Re in the treatment of hepatic tumor

International Nuclear Information System (INIS)

Shyh-Jen Wang; Wan-Yu Lin; Bor-Tsung Hsieh; Kai-Yuan Cheng; Lie-Hang Shen; Ming-Ja Su

2004-01-01

A new method for the synthesis of 188 Re-Lipiodol without using a chelating agent and to evaluate the stability and biodistribution of the new agent in rats with hepatic tumors was attempted. Eighteen male Sprague -Dawley rats with liver tumors were sacrificed at 1, 24, and 48 hours (six rats at each time) after injection of approximately 7.4 MBq (0.2 mCi) of 188 Re Lipiodol via the hepatic artery. Samples of tumor, liver and other organs were collected and tissue concentration (%ID/g) of the markers were calculated. A high level of radioactivity in the hepatic tumors was found at every time of the study. The ratios of tumor to normal liver tissue concentration (T/N ratio) were 7.62 at 1 hour, 8.03 at 24 hours, and 7.70 at 48 hours. Except for the liver, kidneys and lungs, concentrations in other organs were low. The new method for labeling Lipiodol with 188 Re is simple and has potential for the treatment of hepatic tumors. (author)

Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

Directory of Open Access Journals (Sweden)

Christopher Williams

2005-01-01

Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

Effect of hepatic blood flow alteration on the therapeutic effect of cryoablation in VX2 hepatic tumor rabbit: an experimental study

International Nuclear Information System (INIS)

Guo Zhi; Ni Hong; Li Baoguo; Hu Yonghua; Xing Wenge; Liu Fang

2008-01-01

Objective: To investigate the effect of alteration of blood flow in the hepatic artery on the therapeutic effect of cryoablation in VX2 hepatic tumor rabbit model. Methods: Thirty rabbits with VX2 hepatic tumor were divided into three groups according to hepatic artery blood flow: complete occlusion of the hepatic artery(group A), partial occlusion of the hepatic artery (group B), and no occlusion of the hepatic artery (group C). With conventional CT scan and perfusion scan, the values of blood flow (BF) and blood volume(BV) of VX 2 tumor were computed and the differences among the three groups were analyzed. After cryoablation, the animals were euthanized and the livers were removed. The hepatic tissue from the cryoablation area and surrounding area underwent both methyl thiazolyl tetrazolium (MTY) diaphorase staining and triphenyl tetrazolium chloride (TTC) staining. The gross pathology and histopathological changes were observed. Results: (1)The BF and BV in the three groups were: (7.23 + 2. 15 ) ml·100 g -1 ·min -1 and (1.63±0.52) ml/100 g in group A; (32.65±6.12) ml·100 g -1 ·min -1 and (9.32±2.63) ml/100 g in group B; (61.34±12.15) ml·100 g -1 ·min -1 and (17.51± 3.14) ml/100 g in group C, respectively. There were significant differences among the three groups in the BF and BV (F value was 452.16 and 421.33 in the BF and BV, respectively, P <0.01); (2) The maximum diameter of cryoablation-induced necrosis was (2.3±0.3)cm in group A, (1.5±0.2) cm in group B, and (0.8±0.1) cm in group C, respectively. The difference was significant among the groups (F value was 315.32,P <0.01). (3) There were well-defined frozen areas, bordering areas and normal surrounding areas in MTT staining. In group C, positive staining around some blood vessels could be seen. Conclusion: Alteration of the blood flow in the hepatic artery can affect the cryoablation efficacy. With the decrease of hepatic artery blood flow, the efficacy of cryoablation on liver tumor

Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma.

Directory of Open Access Journals (Sweden)

Nina V Chaika

Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways in primary tumor and metastases of patients with pancreatic adenocarcinoma.We analyzed the metabolic gene (those involved in glycolysis, tri-carboxylic acid pathway, pentose-phosphate pathway and fatty acid metabolism expression profiles of primary and metastatic lesions from pancreatic cancer patients by gene expression arrays. We observed two principal results: genes that were upregulated in primary and most of the metastatic lesions; and genes that were upregulated only in specific metastatic lesions in a site-specific manner. Immunohistochemical (IHC analyses of several metabolic gene products confirmed the gene expression patterns at the protein level. The IHC analyses also revealed differential tumor and stromal expression patterns of metabolic enzymes that were correlated with the metastasis sites.Here, we present the first comprehensive studies that establish differential metabolic status of tumor and stromal components and elevation of aerobic glycolysis gene expression in pancreatic cancer.

Number and location of hepatic malignant lesions by computerized tomography-angiography

International Nuclear Information System (INIS)

Llauger, J.; Perez, C.; Castaner, E.; Coscojuela, P.; Marcos, J.A.; Pallardo, Y.; Traid, C.; Zidan, A.

1991-01-01

In order to perform surgical treatment of tumorous hepatic disease, primary or metastatic, the most accurate knowledge as possible of the number and location of lesions is needed. In that way, results provided by echography and conventional CT are not much precise, showing lasser that 60% of lessions. In this study CT-angiography technique, its indications, results and images obtained by this method are described. (Author)

Abdominal Splenosis Mimicking Hepatic Tumor: A Case Report

Directory of Open Access Journals (Sweden)

Ming-Lun Yeh

2008-11-01

Full Text Available Diagnosis of abdominal splenosis is often undiagnosed until treatment for splenic rupture or splenectomy. This report describes a patient with splenosis mimicking hepatic tumor. The patient had a history of splenic trauma with splenectomy and chronic hepatitis C. After routine abdominal ultrasound revealed a liver nodule, further imaging studies, including magnetic resonance imaging, computed tomography and angiography, were performed. After the patient eventually underwent surgery, pathology revealed splenic tissue. Despite its distinguishable clinical features, splenosis is difficult to identify by modern imaging modalities. Therefore, accurate and timely diagnosis of this disease requires constant vigilance.

Peritumoral hemorrhage immediately after radiosurgery for metastatic brain tumor

International Nuclear Information System (INIS)

Uchino, Masafumi; Kitajima, Satoru; Miyazaki, Chikao; Otsuka, Takashi; Seiki, Yoshikatsu; Shibata, Iekado

2003-01-01

We report a case of a 44-year-old woman with metastatic brain tumors who suffered peri-tumoral hemorrhage soon after stereotactic radiosurgery (SRS). She had been suffering from breast cancer with multiple systemic metastasis. She started to have headache, nausea, dizziness and speech disturbance 1 month before admission. There was no bleeding tendency in the hematological examination and the patient was normotensive. Neurological examination disclosed headache and slightly aphasia. Magnetic resonance imaging showed a large round mass lesion in the left temporal lobe. It was a well-demarcated, highly enhanced mass, 45 mm in diameter. SRS was performed on four lesions in a single session (Main mass: maximum dose was 30 Gy in the center and 20 Gy in the margin of the tumor. Others: maximum 25 Gy margin 20 Gy). After radiosurgery, she had severe headache, nausea and vomiting and showed progression of aphasia. CT scan revealed a peritumoral hemorrhage. Conservative therapy was undertaken and the patient's symptoms improved. After 7 days, she was discharged, able to walk. The patient died of extensive distant metastasis 5 months after SRS. Acute transient swelling following conventional radiotherapy is a well-documented phenomenon. However, the present case indicates that such an occurrence is also possible in SRS. We have hypothesized that acute reactions such as brain swelling occur due to breakdown of the fragile vessels of the tumor or surrounding tissue. (author)

A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors

Directory of Open Access Journals (Sweden)

Jerome A. Staal

2016-10-01

Full Text Available Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite this, very little is known regarding the impact of such genomic abnormalities upon the functional biology of the tumor cell. We discuss here how recent advances in quantitative proteomic techniques are now providing new insights into the functional biology of these aggressive tumors, as illustrated by the use of proteomics to bridge the gap between the genotype and phenotype in the case of c-MYC-amplified/associated medulloblastoma. These integrated proteogenomic approaches now provide a new platform for understanding cancer biology by providing a functional context to frame genomic abnormalities.

Low infection rate after tumor hip arthroplasty for metastatic bone disease in a cohort treated with extended antibiotic prophylaxis

DEFF Research Database (Denmark)

Hettwer, Werner H; Horstmann, Peter Frederik; Hovgaard, Thea Bechmann

2015-01-01

tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96...... suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur.......Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic...

Primary hepatic actinomycosis mimicking hepatic malignancy with metastatic lymph nodes by F-18 FDG PET/CT

International Nuclear Information System (INIS)

Kong, Eun Jung

2016-01-01

Hepatic involvement is usually secondary to abdominal actinomycosis infection. Symptom onset is typically subscute and the disease follows a chronic and indolent course. These lesions are called inflammatory pseudotumors and cannot be differentiated from malignant tumors by radiological examination alone. Laboratory tests showed mild anemia; hemoglobin 119 g/L, elevated white blood cell count of 23,060/mm 3 , AST 33 U/L, ALT 45 U/L, and γ-GT 155 U/L.

Primary hepatic actinomycosis mimicking hepatic malignancy with metastatic lymph nodes by F-18 FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Kong, Eun Jung [Yeungnam Univ. Medical School and Hospital, Daegu (Korea, Republic of)

2016-03-15

Hepatic involvement is usually secondary to abdominal actinomycosis infection. Symptom onset is typically subscute and the disease follows a chronic and indolent course. These lesions are called inflammatory pseudotumors and cannot be differentiated from malignant tumors by radiological examination alone. Laboratory tests showed mild anemia; hemoglobin 119 g/L, elevated white blood cell count of 23,060/mm{sup 3}, AST 33 U/L, ALT 45 U/L, and γ-GT 155 U/L.

Vascular Targeting in Pancreatic Cancer: The Novel Tubulin-Binding Agent ZD6126 Reveals Antitumor Activity in Primary and Metastatic Tumor Models

Directory of Open Access Journals (Sweden)

Axel Kleespies

2005-10-01

Full Text Available ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic disease, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic disease could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.

Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

Directory of Open Access Journals (Sweden)

Thorsten Frenzel

Full Text Available Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior.Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

[Imaging manifestations and pathologic basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors].

Science.gov (United States)

Ou, Youkuan; Xiao, Enhua; Shang, Quanliang; Chen, Juan

2015-10-01

To investigate the imaging manifestations of CT, MRI and pathological basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors.
 CT or MRI images and pathological features for hepatic capsular retraction syndrome were retrospectively analyzed in 50 patients with benign and malignant liver tumors. Picture archive and communication system (PACS) was used to observe and compare the morphology, size, width, depth, edge of the capsular retraction and the status of liquid under the liver capsule. The structure, differentiation and proliferation of the tumor were analyzed under the microscope.
 There were malignant liver tumors in 44 patients and benign tumor in 6 patients. The smooth or rough for the edge of capsular retraction was significant difference between the benign tumors and the malignant tumors with three differentiated grades (all PBenign and malignant hepatic tumors may appear capsule retraction syndrome, but there are morphological differences between them. The differences are closely related with the lesion size, differentiated degree of tumor and fibrous tissue proliferation.

Hepatic perivascular epithelioid cell tumor (PEComa: a case report with a review of literatures

Directory of Open Access Journals (Sweden)

Hyun-Jin Son

2017-03-01

Full Text Available Hepatic perivascular epithelioid cell tumors (PEComas are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45 and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA.

Intraarterial infusion chemotherapy for the treatment of metastatic liver cancer

International Nuclear Information System (INIS)

Arai, Yasuaki; Kido, Choichiro

1987-01-01

Some techniques of the most recent interventional radiology are very useful for the treatment of metastatic liver cancer and changing the style of hepatic infusion chemotherapy. This report shows our latest results and methods of hepatic infusion chemotherapy for metastatic liver cancer. 1. For the catheter placement, a new catheterization route via the left subclavian artery into the hepatic artery was developed and performed in 132 cases. Superselective catheterization succeeded in 123 cases (93.2 %). This procedure is less invasive than laparotomy and less troublesome than other percutaneous routes. 2. For useful infusion system, an implantable injection port ''Reservoir'' was developed and it was used in 87 cases. This method makes arterial infusion chemotherapy easy, and imploves their quality of life. 3. To acquire adequate drug delivery, arterial redistribution by steel coils was done, and 109 arteries in 80 cases were occluded. This method is very useful to make multiple hepatic artery single and it is important to avoid gasroduodenal complications. 4. Now, using these techniques, the phase II study of 5FU, ADM, MMC combined hepatic infusion in patients with non-resectable metastatic liver cancer is done. Up to this time, such a phase study on arterial infusion chemotherapy was difficult because of technical problems, but these new techniques make it possible. In conclusion, these new methods change the style and conception of hepatic infusion, and these make much progress on the treatment of patients with metastatic liver cancer. (author)

Preliminary study of spectral CT imaging in the differential diagnosis of metastatic lymphadenopathy due to various tumors

International Nuclear Information System (INIS)

Liu Jingang; Liu Ya; Li Lixin

2011-01-01

Objective: To investigate the feasibility of differentiating lymph node metastases of four types of primary tumors (lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma) using gemstone spectral imaging (GSI). Methods: Three cases with lymphoma (28 lymph node), five cases with lung adenocarcinoma (30 lymph node), four cases with lung squamous cell carcinoma (24 lymph node) and two cases with cholangiocarcinoma (10 lymph node) were evaluated by germstona spectra imaging CT scans. Imaging protocol included unenhanced conventional CT scan (120 kVp), enhanced GSI (80/140 kVp) on arterial phase and conventional CT scan (120 kVp) on portal phase. CT attenuation values of lymph nodes in the monochromatic images at Il sets of keV levels (40- 140 keV, 10 keV step) and the iodine and water contents of these lymph nodes were measured. All results were analyzed with ANOVA and t test. Results: The optimal monochromatic level was 70 keV for the optimal contrast-noise ratio (CNR) of metastatic lymphadenopathy. The CT attenuation values of metastatic lymphadenopathy were (81.36±9.81), (58.33±21.55), (56.47±10.62) and (73.57±4.43) HU, respectively, at 70 keV (F=17.29, P 0.05). The iodine contents of lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma were (1.93±0.04), (1.16±0.15), (1.25±0.21) and (1.44±0.04) g/L, respectively. The water contents of lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma were (1029.40±20.85), (1024.98±11.19), (1022.12±12.94) and (1030.87±10.10) g/L, respectively. Except between lung squamous cell carcinoma and lung adenocarcinoma, the differences in the iodine contents of metastatic lymphadenopathy were significant among tumors (P 0.05 ). Conclusions: Although CT spectral imaging fails to differentiate metastatic lymphadenopathy of lung adenocarcinoma and lung squamous cell carcinoma, it is also a promising method of distinguishing metastatic

A clinical and radiological objective tumor response with somatostatin analogs (SSA in well-differentiated neuroendocrine metastatic tumor of the ileum: a case report

Directory of Open Access Journals (Sweden)

De Divitiis C

2015-03-01

Full Text Available Chiara De Divitiis,1 Claudia von Arx,2 Roberto Carbone,3 Fabiana Tatangelo,4 Elena di Girolamo,5 Giovanni Maria Romano,1 Alessandro Ottaiano,1 Elisabetta de Lutio di Castelguidone,3 Rosario Vincenzo Iaffaioli,1 Salvatore Tafuto1 On behalf of the European Neuroendocrine Tumor Society (ENETS Center of Excellence Multidisciplinary Group for Neuroendocrine Tumors in Naples (Italy 1Department of Abdominal Oncology, National Cancer Institute “Fondazione G. Pascale”, Naples, Italy; 2Department of Clinical Medicine and Surgery, “Federico II” University, Naples, Italy; 3Department of Radiology, 4Department of Pathology, 5Department of Endoscopy, National Cancer Institute “Fondazione G Pascale”, Naples, Italy Abstract: Somatostatin analogs (SSAs are typically used to treat the symptoms caused by neuroendocrine tumors (NETs, but they are not used as the primary treatment to induce tumor shrinkage. We report a case of a 63-year-old woman with a symptomatic metastatic NET of the ileum. Complete symptomatic response was achieved after 1 month of treatment with SSAs. In addition, there was an objective response in the liver, with the disappearance of secondary lesions noted on computed tomography scan after 3 months of octreotide treatment. Our experience suggests that SSAs could be useful for downstaging and/or downsizing well-differentiated NETs, and they could allow surgery to be performed. Such presurgery therapy could be a promising tool in the management of patients with initially inoperable NETs. Keywords: neuroendocrine tumor, somatostatin analogs, octreotide, metastatic tumor of the ileum, radiological tumor response

NATURAL KILLER T CELLS IN HEPATIC LEUCOCYTE INFILTRATES IN PATIENTS WITH MALIGNANT PROCESS AND VIRAL HEPATITIS

Directory of Open Access Journals (Sweden)

O. V. Lebedinskaya

2010-01-01

Full Text Available Morphology, topography, and immunohistochemical features of leukocyte infiltrates were studied in various sites of the liver samples from the patients with metastatic disease, been affected by hepatitis B and C viruses at different degree of activity. Liver of СВА mice with implanted САО-1 tumour was also under study. Histochemical, and functional features, as well as immune phenotype of these cells were investigated. It has been shown that the major fraction of leukocyte infiltrates, mostly associated with implanted tumours in experimental mice, and in the areas adjacent to the tumor in humans, like as on the peak of viral hepatitis activity, is composed of lymphocytes. They are presented by large numvers of activated proliferating and differentiating cells bearing specific antigens, as well as natural killers and T-lymphocytes, possessing high-level killer activity towards NK-sensitive, and autologous lines of cancer cells. Hence, the results of our study, generally, confirm the data from literature reporting on existence of a special lymphocyte subpopulation, NKT cells, in human or murine liver affected by hepatitis virus or malignant tumors. The data concerning functional properties of these cells may be used for development of immunotherapy methods of viral diseases and oncological conditions complicated by liver metastases.

Transcription of a novel mouse semaphorin gene, M-semaH, correlates with the metastatic ability of mouse tumor cell lines

DEFF Research Database (Denmark)

Christensen, C R; Klingelhöfer, Jörg; Tarabykina, S

1998-01-01

identified a novel member of the semaphorin/collapsin family in the two metastatic cell lines. We have named it M-semaH. Northern hybridization to a panel of tumor cell lines revealed transcripts in 12 of 12 metastatic cell lines but in only 2 of 6 nonmetastatic cells and none in immortalized mouse...

Optimal radiation port arrangements for hepatic tumor using 3-dimensional conformal radiotherapy planning

Energy Technology Data Exchange (ETDEWEB)

Lee, Ik Jae; Seong, Jin Sil; Shim, Su Jung; Jeong, Kyoung Keun [Yonsei Univ., Seoul (Korea, Republic of); Cho, Kwang Hwan [Sunchunhyang Univ., Buchon (Korea, Republic of)

2006-12-15

The purpose of this study was to investigate the optimal beam arrangements for hepatic tumors, according to the location of the hepatic tumor and its relationship to Organs At Risk (OARs). The virtual gross tumor volumes were divided into four groups according to the Couinaud's classification. Several plans were made for each virtual target, and these plans were compared for the Normal Tissue Complication Probabilities (NTCP). For group I, NTCP improved as the number of the beam ports increased. However, plans with more than 5 ports had little advantage. For group II, plans with the beam directions from the anterior side showed better results. Group III contained many OARs near the target, which placed restrictions on the beam-directions. Multi-directional plans yielded a higher dose to the OARs than a simple two-port plan using right anterior oblique and posterior beam (RAO/PA). For group IV, a simple RAO/PA port plan was adequate for protection of remaining liver. NTCP can significantly vary between radiotherapy plans when the location of the tumor and its neighboring OARs are taken into consideration. The results in this study of optimal beam arrangements could be a useful set of guidelines for radiotherapy of hepatic tumors.

Microscopic validation of whole mouse micro-metastatic tumor imaging agents using cryo-imaging and sliding organ image registration

OpenAIRE

Liu, Yiqiao; Zhou, Bo; Qutaish, Mohammed; Wilson, David L.

2016-01-01

We created a metastasis imaging, analysis platform consisting of software and multi-spectral cryo-imaging system suitable for evaluating emerging imaging agents targeting micro-metastatic tumor. We analyzed CREKA-Gd in MRI, followed by cryo-imaging which repeatedly sectioned and tiled microscope images of the tissue block face, providing anatomical bright field and molecular fluorescence, enabling 3D microscopic imaging of the entire mouse with single metastatic cell sensitivity. To register ...

Multiple urinary bladder masses from metastatic prostate adenocarcinoma

Directory of Open Access Journals (Sweden)

Richard Choo

2010-12-01

Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

Quantitative hepatic CT perfusion measurement: Comparison of Couinaud's hepatic segments with dual-source 128-slice CT

Energy Technology Data Exchange (ETDEWEB)

Wang, Xuan [The Department of Radiology, Peking Union Medical College Hospital, Dongcheng District, Beijing, 100730 (China); Xue, Hua-dan, E-mail: bjdanna95@hotmail.com [The Department of Radiology, Peking Union Medical College Hospital, Dongcheng District, Beijing, 100730 (China); Jin, Zheng-yu, E-mail: jin_zhengyu@163.com [The Department of Radiology, Peking Union Medical College Hospital, Dongcheng District, Beijing, 100730 (China); Su, Bai-yan; Li, Zhuo; Sun, Hao; Chen, Yu; Liu, Wei [The Department of Radiology, Peking Union Medical College Hospital, Dongcheng District, Beijing, 100730 (China)

2013-02-15

Purpose: To compare the quantitative liver computed tomography perfusion (CTP) differences among eight hepatic segments. Materials and methods: This retrospective study was based on 72 acquired upper abdomen CTP scans for detecting suspected pancreas tumor. Patients with primary or metastatic liver tumor, any focal liver lesions except simple cyst (<3 cm in diameter), history of liver operation or splenectomy, evidence of liver cirrhosis or invasion of portal vein were excluded. The final analysis included 50 patients (M:F = 21:29, mean age = 43.2 years, 15–76 years). Arterial liver perfusion (ALP), portal-venous perfusion (PVP), total hepatic perfusion (THP = ALP + PVP), and hepatic perfusion index (HPI) of each hepatic segment were calculated and compared by means of one-way analysis of variance (ANOVA) and the Bonferonni correction method. Results: Compared to hepatic segments 5, 6, 7 and 8, segments 2 and 3 showed a tendency of higher ALPs, lower PVPs, and higher HPIs, most of which were statistically significant (p < 0.05). Hepatic segments 1 and 4 had higher mean values of ALP and HPI and lower mean values of PVP than segments 5, 6, 7 and 8 as well, although no significant differences were detected except for ALP and HPI for liver segments 1 and 7 (p = 0.001 and 0.035 respectively), and ALP for liver segments 1 and 5 (p = 0.039). Higher ALP and HPI were showed in hepatic segment 3 compared to segment 4 (p = 0.000 and 0.000 respectively). No significant differences were found for THP among eight segments. Conclusions: Intra-hepatic perfusion differences exist in normal hepatic parenchyma especially between lateral sector (segments 2 and 3) and right lobe (segments 5, 6, 7 and 8). This might have potential clinical significance in liver-perfusion-related protocol design and result analysis.

Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties.

Directory of Open Access Journals (Sweden)

Pegah Ghiabi

Full Text Available Treating metastasis has been challenging due to tumors complexity and heterogeneity. This complexity is partly related to the crosstalk between tumor and its microenvironment. Endothelial cells -the building blocks of tumor vasculature- have been shown to have additional roles in cancer progression than angiogenesis and supplying oxygen and nutrients. Here, we show an alternative role for endothelial cells in supporting breast cancer growth and spreading independent of their vascular functions. Using endothelial cells and breast cancer cell lines MDA-MB231 and MCF-7, we developed co-culture systems to study the influence of tumor endothelium on breast tumor development by both in vitro and in vivo approaches. Our results demonstrated that endothelial cells conferred survival advantage to tumor cells under complete starvation and enriched the CD44HighCD24Low/- stem cell population in tumor cells. Moreover, endothelial cells enhanced the pro-metastatic potential of breast cancer cells. The in vitro and in vivo results concordantly confirmed a role for endothelial Jagged1 to promote breast tumor through notch activation. Here, we propose a role for endothelial cells in enhancing breast cancer progression, stemness, and pro-metastatic traits through a perfusion-independent manner. Our findings may be beneficial in developing novel therapeutic approaches.

Intracardiac Metastatic Rhabdomyosarcoma

Directory of Open Access Journals (Sweden)

Tae Ho Kim

2015-12-01

Full Text Available A 70-year-old man who visited Samsung Medical Center reported experiencing palpitation for 2 weeks. He had undergone excision of a mass in the right buttock due to rhabdomyosarcoma 7 years prior to this visit. Transesophageal echocardiography showed a pedunculated mass in the left ventricle, which was thought to be a vegetation of infective endocarditis, metastasis of the primary tumor, or thrombus. He underwent removal of the cardiac tumor, and the pathologic report was metastatic rhabdomyosarcoma. Thus, here, we report a rare case of metastatic rhabdomyosarcoma in the left ventricle.

Androgen receptor expression on circulating tumor cells in metastatic breast cancer.

Directory of Open Access Journals (Sweden)

Takeo Fujii

Full Text Available Androgen receptor (AR is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+ breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer.Blood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK, and biomarkers of interest (AR, estrogen receptor [ER], and HER2 on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms.Of 68 patients, 51 (75% had at least 1 CTC, and 49 of these 51 (96% had hormone-receptor-positive (HR+/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells.CTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their heterogeneity.

The detectability of hepatic metastases in candidates of radiofrequency ablation: comparison for helical CT scanning and late-phase pulse-inversion harmonic imaging

Energy Technology Data Exchange (ETDEWEB)

Lee, Kang Won; Yoon, Kwon Ha; Kim, Eun A; Park, Ki Han; Juhng, Seon Kwan; Won, Jong Jin [School of Medicine, Wonkwang Univ., Iksan (Korea, Republic of)

2002-02-01

To compare dual-phase helical CT and pulse inversion harmonic US using microbubble contrast agents in the detection of hepatic metastases prior to radiofrequency (RF) ablation. Twenty-one patients in whom hepatic metastases from colorectal cancer had been diagnosed by dual-phase CT scanning and who were considered to be candidates for RF ablation underwent pulse-inversion barmonic US examination. Images were obtained 5 minutes after the bolus injection of microbubble contrast agent SH U 508 A (4.0 g, 300 mg/mL). The number of metastatic tumors revealed by CT and US was determined, and the findings were statistically analysed. The influence of the results of US examination on treatment planning was also evaluated. In 21 patients, 48 metastaic lesions were detected by helical CT, and 56 lesions by US. These eight additional lesions revealed by US occurred in six patients (29%), and their diameter was 3-13 (mean, 7.2) mm. In three of these patients, RF ablation could not be performed ,while in the other three, the additional lesions were ablated. Pulse-inversion harmonic US imaging using microbubble contrast agents may depict small hepatic metastatic tumors that were not apparent at CT. US-therefore appears to be useful in the planning of treatment prior to the RF ablation of hepatic metastases.

Tumor mutational load and immune parameters across metastatic Renal Cell Carcinoma (mRCC) risk groups

Science.gov (United States)

de Velasco, Guillermo; Miao, Diana; Voss, Martin H.; Hakimi, A. Ari; Hsieh, James J.; Tannir, Nizar M.; Tamboli, Pheroze; Appleman, Leonard J.; Rathmell, W. Kimryn; Van Allen, Eliezer M.; Choueiri, Toni K.

2016-01-01

Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared to patients with favorable or intermediate-risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole exome transcriptome data in RCC patients (n = 54) included in The Cancer Genome Atlas that ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by MSKCC risk group, nor was the expression of cytolytic genes –granzyme A and perforin – or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis found that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. PMID:27538576

CAR-T cell therapy in gastrointestinal tumors and hepatic carcinoma: From bench to bedside.

Science.gov (United States)

Zhang, Qi; Zhang, Zimu; Peng, Meiyu; Fu, Shuyu; Xue, Zhenyi; Zhang, Rongxin

2016-01-01

The chimeric antigen receptor (CAR) is a genetically engineered receptor that combines a scFv domain, which specifically recognizes the tumor-specific antigen, with T cell activation domains. CAR-T cell therapies have demonstrated tremendous efficacy against hematologic malignancies in many clinical trials. Recent studies have extended these efforts to the treatment of solid tumors. However, the outcomes of CAR-T cell therapy for solid tumors are not as remarkable as the outcomes have been for hematologic malignancies. A series of hurdles has arisen with respect to CAR-T cell-based immunotherapy, which needs to be overcome to target solid tumors. The major challenge for CAR-T cell therapy in solid tumors is the selection of the appropriate specific antigen to demarcate the tumor from normal tissue. In this review, we discuss the application of CAR-T cells to gastrointestinal and hepatic carcinomas in preclinical and clinical research. Furthermore, we analyze the usefulness of several specific markers in the study of gastrointestinal tumors and hepatic carcinoma.

Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell Tumor

Directory of Open Access Journals (Sweden)

Anoopa A. Koshy MD

2013-01-01

Full Text Available A 56-year-old woman presented to our clinic for recurrent hypoglycemia after undergoing resection of an incidentally discovered nonfunctional pancreatic endocrine tumor 6 years ago. She underwent a distal pancreatectomy and splenectomy, after which she developed diabetes and was placed on an insulin pump. Pathology showed a pancreatic endocrine neoplasm with negative islet hormone immunostains. Two years later, computed tomography scan of the abdomen showed multiple liver lesions. Biopsy of a liver lesion showed a well-differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six years later, she presented to clinic with 1.5 years of recurrent hypoglycemia. Laboratory results showed elevated proinsulin, insulin levels, and c-peptide levels during a hypoglycemic episode. Computed tomography scan of the abdomen redemonstrated multiple liver lesions. Repeated transarterial catheter chemoembolization and microwave thermal ablation controlled hypoglycemia. The unusual features of interest of this case include the transformation of nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the occurrence of atrial flutter after octreotide for treatment.

Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer.

Science.gov (United States)

Priceman, Saul J; Gerdts, Ethan A; Tilakawardane, Dileshni; Kennewick, Kelly T; Murad, John P; Park, Anthony K; Jeang, Brook; Yamaguchi, Yukiko; Yang, Xin; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E; Wu, Anna M; Brown, Christine E; Forman, Stephen J

2018-01-01

Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies.

The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds.

Science.gov (United States)

Rutkowski, Melanie R; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Conejo-Garcia, Jose R

2015-01-01

During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. © 2015 Elsevier Inc. All rights reserved.

Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models

Directory of Open Access Journals (Sweden)

Fabrice Le Boeuf

2017-09-01

Full Text Available The reovirus fusion-associated small transmembrane (FAST proteins are the smallest known viral fusogens (∼100–150 amino acids and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant encoding the p14 FAST protein (VSV-p14 was compared with a similar construct encoding GFP (VSV-GFP in cell culture and syngeneic BALB/c tumor models. Compared with VSV-GFP, VSV-p14 exhibited increased oncolytic activity against MCF-7 and 4T1 breast cancer spheroids in culture and reduced primary 4T1 breast tumor growth in vivo. VSV-p14 prolonged survival in both primary and metastatic 4T1 breast cancer models, and in a CT26 metastatic colon cancer model. As with VSV-GFP, VSV-p14 preferentially replicated in vivo in tumors and was cleared rapidly from other sites. Furthermore, VSV-p14 increased the numbers of activated splenic CD4, CD8, natural killer (NK, and natural killer T (NKT cells, and increased the number of activated CD4 and CD8 cells in tumors. FAST proteins may therefore provide a multi-pronged approach to improving oncolytic virotherapy via syncytium formation and enhanced immune stimulation.

The role of CT in diagnosing small hepatic tumors; Usefulness of table incremental dynamic CT (ICT)

Energy Technology Data Exchange (ETDEWEB)

Usuki, Noriaki; Daikokuya, Hideo; Fukuda, Haruyuki; Saiwai, Shigeo; Nakajima, Hideyuki; Miyamoto, Takeshi; Kudo, Masatoshi (Kobe General Hospital, Hyogo (Japan))

1992-11-01

Twenty-seven cases of small hepatic tumors were examined by MRI and CT (ICT). MRI was more sensitive than plain and contrast CT. But ICT could detect more small lesions than MRI. CT is not more superior modality than MRI untill ICT is performed. It is concluded ICT should be done when diagnosing small hepatic tumors by CT. (author).

Hepatic parenchymal changes following transcatheter embolization and chemoembolization in a rabbit tumor model.

Directory of Open Access Journals (Sweden)

Yong Wang

Full Text Available OBJECTIVE: To compare the effects of transcatheter arterial chemoembolization (TACE with transcatheter arterial embolization (TAE on liver function, hepatic damage, and hepatic fibrogenesis in a rabbit tumor model. MATERIALS AND METHODS: Thirty-nine New Zealand white rabbits implanted with VX2 tumors in the left liver lobes were randomly divided into three groups: TAE, TACE, and control group. In the TAE group (n = 15, polyvinyl alcohol particles (PVAs were used for left hepatic artery embolization. In the TACE group (n = 15, the tumors were treated with left hepatic arterial infusions of a suspension of 10-hydroxycamptothecin and lipiodol, followed by embolization with PVAs. In the control group (n = 9, the animals received sham treatment with distilled water. Serum and liver samples were collected at 6 hours, 3 days and 7 days after treatment. Liver damage was measured using a liver function test and histological analyses. Liver fibrogenesis and hepatic stellate cell (HSC activation were evaluated using Sirius Red and anti-alpha-smooth muscle actin (α-SMA immunohistochemical stains. RESULTS: TACE caused liver injury with greater increases in serum alanine aminotransferase and aspartate aminotransferase levels on day 3 (P<0.05. Histological analyses revealed increased hepatic necrosis in adjacent non-tumorous liver tissue from day 3 compared to the TAE group (Suzuki score of 2.33±1.29 versus 1.13±1.18, P = 0.001. HSC activation and proliferation were significantly increased in the TACE group compared to the control group at 3 and 7 days after treatment (0.074±0.014 vs. 0.010±0.006, and 0.088±0.023 vs. 0.017±0.009, P<0.05. Sirius Red staining demonstrated a statistically significant increase in collagen deposition in the livers in the TACE group 7 days after embolization compared to the control group (0.118±0.012 vs. 0.060±0.017, P = 0.05. CONCLUSION: The results of this animal study revealed that TACE induced

Evaluation of Tumor Viability for Primary and Bone Metastases in Metastatic Castration-Resistant Prostate Cancer Using Whole-Body Magnetic Resonance Imaging

Directory of Open Access Journals (Sweden)

Hiromichi Iwamura

2018-01-01

Full Text Available In contrast to bone scan and computed tomography (CT, which depend on osteoblastic response to detect bone metastasis, whole-body magnetic resonance imaging (WB-MRI may be able to directly detect viable tumors. A 75-year-old male who had progressive metastatic prostate cancer during primary androgen deprivation therapy was referred to our hospital. Although bone scan and CT showed multiple bone metastases, WB-MRI suggested nonviable bone metastasis and viable tumor of the primary lesion. Prostate needle biopsy demonstrated viable prostate cancer cells from 10 of 12 cores. In contrast, CT-guided needle biopsy from bone metastasis of the lumbar vertebra revealed no malignant cells. Based on these findings, we reasoned that viable tumor cells inducing disease progression may primarily exist in the primary lesions and not in the metastatic lesions, and combined prostate radiotherapy and systemic hormonal therapy resulted in successful clinical response and disease control. The use of WB-MRI to detect viable disease lesions may enable us to design optimal treatment strategies for patients with metastatic castration-resistant prostate cancer.

Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer.

Science.gov (United States)

Kim, Dalyong; Kim, Sun Young; Lee, Ji Sung; Hong, Yong Sang; Kim, Jeong Eun; Kim, Kyu-Pyo; Kim, Jihun; Jang, Se Jin; Yoon, Young-Kwang; Kim, Tae Won

2017-11-23

In metastatic colorectal cancer, the location of the primary tumor has been suggested to have biological significance. In this study, we investigated whether primary tumor location affects cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer. Genotyping by the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA, and BRAF was performed in tumors from 307 patients who had been given cetuximab as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those with multiple primary location (n = 10) were excluded. Right colon cancer was defined as a tumor located in the proximal part to splenic flexure. A total of 170 patients were included in the study (right versus left, 23 and 147, respectively). Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer. Right colon cancer showed poorer progression-free survival (2.0 vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P < 0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF mutation, right colon primary, poorly differentiated histology, and peritoneal involvement were associated with risk of death. In RAS wild-type colon cancer treated with cetuximab as salvage treatment, right colon primary was associated with poorer survival outcomes than left colon and rectal cancer.

Peritumoral hemorrhage after radiosurgery for metastatic brain tumor; A case report

Energy Technology Data Exchange (ETDEWEB)

Motozaki, Takahiko (Nishinomiya City General Hospital, Hyogo (Japan)); Ban, Sadahiko; Yamamoto, Toyoshiro; Hamasaki, Masatake

1994-08-01

An unusual case of peritumoral hemorrhage after radiosurgery for the treatment of metastatic brain tumor is reported. This 64-year-old woman had a history of breast cancer and underwent right mastectomy in 1989. She remained well until January 1993, when she started to have headache, nausea and speech disturbance, and was hospitalized on February 25, 1993. Neurological examination disclosed right hemiparesis and bilateral papilledema. CT scan and MR imaging showed a solitary round mass lesion in the left basal ganglia region. It was a well-demarcated, highly enhanced mass, 37 mm in diameter. Cerebral angiography confirmed a highly vascular mass lesion in the same location. She was treated with radiosurgery on March 8 (maximum dose was 20 Gy in the center and 10 Gy in the peripheral part of the tumor). After radiosurgery, she had an uneventful course and clinical and radiosurgical improvement could be detected. Her neurological symptoms and signs gradually improved and reduction of the tumor size and perifocal edema could be seen one month after radiosurgery. However, 6 weeks after radiosurgery, she suddenly developed semicoma and right hemiplegia. CT scan disclosed a massive peritumoral hemorrhage. Then, emergency craniotomy, evacuation of the hematoma and total removal of the tumor were performed on April 24. Histopathological diagnosis was adenocarcinoma. It was the same finding as that of the previous breast cancer. Histopathological examination revealed necrosis without tumor cells in the center and residual tumor cells in the peripheral part of the tumor. It is postulated that peritumoral hemorrhage was caused by hemodynamic changes in the vascular-rich tumor after radiosurgery and breakdown of the fragile abnormal vessels in the peripheral part of the tumor. (author).

[A case report-advanced pancreas cancer with liver and lung metastases well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting].

Science.gov (United States)

Hasuike, Yasunori; Tanigawa, Takahiko; Yamada, Masaharu; Minami, Yukiko; Ezumi, Koji; Kashiwazaki, Masaki; Fujimoto, Takayoshi

2008-11-01

We report a case of advanced pancreatic cancer with liver and lung metastases that was well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting. The patient was a 74-year-old woman. Chief complaints were back pain and anorexia. She was diagnosed with pancreas cancer with liver and lung metastases at the time of first visit. We started systemic chemotherapy with gemcitabine 1 g/body and 5-FU 1 g/body alternately every other week on an outpatient basis. At 1.5 months (M) after initiation of chemotherapy, we started radiation therapy to the main tumor at a total dose of 40 Gy. After radiation, chemotherapy was resumed. As a result, the size of the main tumor decreased but metastatic liver tumors got larger. Then we changed to combination therapy with systemic chemotherapy (gemcitabine and 5-FU) and hepatic arterial infusion (5-FU weekly). Liver metastases almost disappeared after 7.5 M. Despite all these treatments, however, the number of metastatic lung tumors increased. The patient was hospitalized for 15 M and died after 17 M. We focused on and succeeded in the prolongation of lifetime and maintenance of QOL by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion therapy.

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

Science.gov (United States)

Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

2015-01-01

We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

Radiofrequency ablation of pulmonary tumors

Energy Technology Data Exchange (ETDEWEB)

Crocetti, Laura, E-mail: l.crocetti@med.unipi.i [Division of Diagnostic Imaging and Intervention, Department of Liver Transplants, Hepatology and Infectious Diseases, Pisa University School of Medicine (Italy); Lencioni, Riccardo [Division of Diagnostic Imaging and Intervention, Department of Liver Transplants, Hepatology and Infectious Diseases, Pisa University School of Medicine (Italy)

2010-07-15

The development of image-guided percutaneous techniques for local tumor ablation has been one of the major advances in the treatment of solid tumors. Among these methods, radiofrequency (RF) ablation is currently established as the primary ablative modality at most institutions. RF ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma when liver transplantation or surgical resection are not suitable options and is considered as a viable alternate to surgery for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer. Recently, RF ablation has been demonstrated to be a safe and valuable treatment option for patients with unresectable or medically inoperable lung malignancies. Resection should remain the standard therapy for non-small cell lung cancer (NSCLC) but RF ablation may be better than conventional external-beam radiation for the treatment of the high-risk individual with NSCLC. Initial favourable outcomes encourage combining radiotherapy and RF ablation, especially for treating larger tumors. In the setting of colorectal cancer lung metastases, survival rates provided by RF ablation in selected patients, are substantially higher than those obtained with any chemotherapy regimens and provide indirect evidence that RF ablation therapy improves survival in patients with limited lung metastatic disease.

Mangiferin, a novel nuclear factor kappa B-inducing kinase inhibitor, suppresses metastasis and tumor growth in a mouse metastatic melanoma model

Energy Technology Data Exchange (ETDEWEB)

Takeda, Tomoya; Tsubaki, Masanobu; Sakamoto, Kotaro; Ichimura, Eri; Enomoto, Aya; Suzuki, Yuri [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan); Itoh, Tatsuki [Department of Food Science and Nutrition, Kinki University School of Agriculture, Nara, Nara (Japan); Imano, Motohiro [Department of Surgery, Kinki University School of Medicine, Osakasayama, Osaka (Japan); Tanabe, Genzoh; Muraoka, Osamu [Laboratory of Pharmaceutical Organic Chemistry, School of Pharmacy, Kinki University, Kowakae, Higashi-, Osaka (Japan); Matsuda, Hideaki [Department of Natural Drugs Resources, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan); Satou, Takao [Department of Pathology, Kinki University School of Medicine, Osakasayama, Osaka (Japan); Nishida, Shozo, E-mail: nishida@phar.kindai.ac.jp [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan)

2016-09-01

Advanced metastatic melanoma, one of the most aggressive malignancies, is currently without reliable therapy. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone and exerts many beneficial biological activities. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we evaluated the effect of mangiferin on metastasis and tumor growth in a mouse metastatic melanoma model. We found that mangiferin inhibited spontaneous metastasis and tumor growth. Furthermore, mangiferin suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated NF-κB-inducing kinase (NIK), inhibitor of kappa B kinase (IKK), and inhibitor of kappa B (IκB) and increases the expression of IκB protein in vivo. In addition, we found that mangiferin inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs) in vivo. Mangiferin treatment also increased the expression of cleaved caspase-3, cleaved Poly ADP ribose polymerase-1 (PARP-1), p53 upregulated modulator of apoptosis (PUMA), p53, and phosphorylated p53 proteins, and decreased the expression of Survivin and Bcl-associated X (Bcl-xL) proteins in vivo. These results indicate that mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation, thereby inhibiting metastasis and tumor growth. Importantly, the number of reported NIK selective inhibitors is limited. Taken together, our data suggest that mangiferin may be a potential therapeutic agent with a new mechanism of targeting NIK for the treatment of metastatic melanoma. - Highlights: • Mangiferin prolongs survival in mice by inhibiting metastasis and tumor growth • Mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation • Mangiferin regulates the expression of MMPs, VLAs, and apoptosis regulatory proteins.

Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

Directory of Open Access Journals (Sweden)

Natalie Turner

2014-03-01

Full Text Available Circulating tumor cell (CTC count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

Patterns of somatic alterations between matched primary and metastatic colorectal tumors characterized by whole-genome sequencing.

Science.gov (United States)

Xie, Tao; Cho, Yong Beom; Wang, Kai; Huang, Donghui; Hong, Hye Kyung; Choi, Yoon-La; Ko, Young Hyeh; Nam, Do-Hyun; Jin, Juyoun; Yang, Heekyoung; Fernandez, Julio; Deng, Shibing; Rejto, Paul A; Lee, Woo Yong; Mao, Mao

2014-10-01

Colorectal cancer (CRC) patients have poor prognosis after formation of distant metastasis. Understanding the molecular mechanisms by which genetic changes facilitate metastasis is critical for the development of targeted therapeutic strategies aimed at controlling disease progression while minimizing toxic side effects. A comprehensive portrait of somatic alterations in CRC and the changes between primary and metastatic tumors has yet to be developed. We performed whole genome sequencing of two primary CRC tumors and their matched liver metastases. By comparing to matched germline DNA, we catalogued somatic alterations at multiple scales, including single nucleotide variations, small insertions and deletions, copy number aberrations and structural variations in both the primary and matched metastasis. We found that the majority of these somatic alterations are present in both sites. Despite the overall similarity, several de novo alterations in the metastases were predicted to be deleterious, in genes including FBXW7, DCLK1 and FAT2, which might contribute to the initiation and progression of distant metastasis. Through careful examination of the mutation prevalence among tumor cells at each site, we also proposed distinct clonal evolution patterns between primary and metastatic tumors in the two cases. These results suggest that somatic alterations may play an important role in driving the development of colorectal cancer metastasis and present challenges and opportunities when considering the choice of treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of 1H-MRS-detected metabolic characteristics in single metastatic brain tumors of different origin

International Nuclear Information System (INIS)

Chernov, M.F.; Ono, Yuko; Kubo, Osami; Hori, Tomokatsu

2006-01-01

Various types of intracranial metastases exhibit different growth patterns, which can be reflected in their metabolic characteristics and investigated noninvasively by proton magnetic resonance spectroscopy ( 1 H-MRS). The objective of the present study was comparison of the 1 H-MRS-detected metabolic parameters in brain metastases of different origin. Twenty-five patients (15 men and 10 women; mean age, 62.0 years) with single, previously nontreated metastatic brain tumors were investigated by long-echo single-voxel volume-selected 1 H-MRS. The primary cancer was located in the lungs (10 cases), colon and rectum (8 cases), breast (3 cases), kidney (2 cases), prostate (1 case), and cardiac muscle (1 case). Comparison of clinical and radiological variables, including type of tumor contrast enhancement and extension of peritumoral edema, did not disclose statistically significant differences in metastatic brain tumors of different origin. At the same time, comparison of 1 H-MRS-detected metabolic characteristics revealed that metastases of colorectal carcinoma have greater content of mobile lipids (Lip) compared to other neoplasms. In conclusion, high Lip content in the viable brain metastases of colorectal carcinoma can be used as an additional diagnostic clue for noninvasive identification of these tumors and should be taken into consideration in cases of 1 H-MRS-based differentiation of their recurrence and radiation-induced necrosis after radiosurgical or radiotherapeutic treatment. (author)

Indicação e tratamento dos tumores benignos do fígado Indication and treatment of benign hepatic tumors

Directory of Open Access Journals (Sweden)

Júlio Cezar Uili Coelho

2011-12-01

Full Text Available INTRODUÇÃO: Os tumores hepáticos benignos ocorrem em 9% da população. A grande maioria dessas neoplasias é diagnosticada em pacientes assintomáticos durante a realização de exames de imagem de rotina. OBJETIVO: Apresentar os principais aspectos das indicações e tratamento dos tumores hepáticos benignos. MÉTODOS: Foi realizada revisão de literatura baseada em pesquisa no PubMed, Bireme e Scielo cruzando os descritores neoplasia hepática, hemangioma, adenoma e hiperplasia nodular focal. Foram selecionados, estudos de técnicas cirúrgicas e acrescentada a experiência dos autores. O hemangioma é o tumor hepático mais comum, sendo identificado entre 5% e 7% das necropsias. É mais comum nas mulheres entre as 3ª e 5ª décadas da vida e pode aumentar de tamanho na gravidez e com a administração de estrogênios. Apesar de não estabelecida, a sua causa está relacionada com os hormônios sexuais. As complicações incluem inflamação, coagulopatia, sangramento e compressão de estruturas vizinhas. Rotura espontânea é excepcional, com somente 35 casos descritos na literatura internacional. O adenoma e a hiperplasia nodular focal predominam no sexo feminino e na faixa etária de 20 a 40 anos. Enquanto o primeiro requer ressecção hepática pelo risco de sangramento e malignização, o segundo deve ter conduta expectante. CONCLUSÕES: Os tumores hepáticos benignos mais comuns são em ordem decrescente de frequência o hemangioma, hiperplasia nodular focal e o adenoma. A diferenciação entre tumores benignos e malignos é geralmente realizada com segurança com base nos dados clínicos e nos exames de imagem. O hemangioma e a hiperplasia nodular focal geralmente tem conduta expectante, enquanto que o adenoma requer ressecção pelo risco de hemorragia e de transformação em carcinoma.BACKGROUND: Benign hepatic tumors occur in 9% of the population. The majority is diagnosed in asymptomatic patients during routine imaging exams

Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer

Science.gov (United States)

Priceman, Saul J.; Gerdts, Ethan A.; Tilakawardane, Dileshni; Kennewick, Kelly T.; Murad, John P.; Park, Anthony K.; Jeang, Brook; Yamaguchi, Yukiko; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E.; Brown, Christine E.; Forman, Stephen J.

2018-01-01

ABSTRACT Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. PMID:29308300

Massive hematemesis after radiofrequency ablation of metastatic liver tumor with successful hemostasis achieved through transarterial embolization.

Science.gov (United States)

Liu, Chien-An; Chiu, Nai-Chi; Chiou, Yi-You

2018-03-03

Hemorrhagic complications are the most common major complications that occur after radiofrequency ablation, but hematemesis as a complication after radiofrequency ablation for hepatic tumor has not been mentioned before. A hepatogastric fistula as a delayed complication is also rare. We present the case of a 77-year-old man with severe hematemesis that occurred 2 months after radiofrequency ablation of a liver metastasis of gastric cancer. A ruptured hepatic artery pseudoaneurysm and a hepatogastric fistula were confirmed through serial imaging examinations. The current case is reported in combination with 2 rare major complications after radiofrequency ablation of a liver tumor. Copyright © 2018. Published by Elsevier Inc.

Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer.

Science.gov (United States)

Shiomi-Mouri, Yukako; Kousaka, Junko; Ando, Takahito; Tetsuka, Rie; Nakano, Shogo; Yoshida, Miwa; Fujii, Kimihito; Akizuki, Miwa; Imai, Tsuneo; Fukutomi, Takashi; Kobayashi, Katsumasa

2016-01-01

Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3. We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios. With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p CEA and CA15-3.

Malignant bone tumors

International Nuclear Information System (INIS)

Zedgenidze, G.A.; Kishkovskij, A.N.; Elashov, Yu.G.

1984-01-01

Clinicoroentgenologic semiotics of malignant bone tumors as well as metastatic bone tumors are presented. Diagnosis of malignant and metastatic bone tumors should be always complex, representing a result of cooperation of a physician, roentgenologist, pathoanatomist

Computed tomography of hepatocellular carcinoma

International Nuclear Information System (INIS)

Choi, Soomi; Nakamura, Hitonobu; Tanaka, Ken; Hori, Shinichi; Tokunaga, Kou

1983-01-01

Based on a series of CT of the liver in 125 patients with hepatoma and 45 patients with metastatic hepatic tumors, the mode of dilatation of the intrahepatic bile duct was examined. In patients with hepatoma, partia dilatations of intrahepatic bile duct were more commonly seen than general dilatations. On the other hand, there was no case of partial dilatation of the intrahepatic bile duct in patients with metastatic hepatic tumors. It could be concluded that partial dilatation of the intrahepatic bile duct is an useful CT finding to make a diagnosis of hepatoma, particularly to differentiate hepatoma from metastatic hepatic tumor. (author)

Computed tomography of hepatocellular carcinoma. Dilatation of intrahepatic bile duct

Energy Technology Data Exchange (ETDEWEB)

Choi, Soomi; Nakamura, Hitonobu; Tanaka, Ken; Hori, Shinichi; Tokunaga, Kou [Osaka Univ. (Japan). Faculty of Medicine

1983-10-01

Based on a series of CT of the liver in 125 patients with hepatoma and 45 patients with metastatic hepatic tumors, the mode of dilatation of the intrahepatic bile duct was examined. In patients with hepatoma, partia dilatations of intrahepatic bile duct were more commonly seen than general dilatations. On the other hand, there was no case of partial dilatation of the intrahepatic bile duct in patients with metastatic hepatic tumors. It could be concluded that partial dilatation of the intrahepatic bile duct is an useful CT finding to make a diagnosis of hepatoma, particularly to differentiate hepatoma from metastatic hepatic tumor.

THE TUMOR MACROENVIRONMENT: CANCER-PROMOTING NETWORKS BEYOND TUMOR BEDS

OpenAIRE

Rutkowski, Melanie R.; Svoronos, Nikolaos; Puchalt, Alfredo Perales; Conejo-Garcia, Jose R.

2015-01-01

During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, and myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the mac...

A new technique for localization of hepatic tumors that are poorly visible with CT fluoroscopy

International Nuclear Information System (INIS)

Arrive, Lionel; Azizi, Louisa; Monnier-Cholley, Laurence; Lewin, Maite; Tubiana, Jean-Michel; Rosmorduc, Olivier; Beaussier, Marc

2006-01-01

The purpose of this study was to report a new technique for localization of hepatic tumors that are poorly visible with CT fluoroscopy. Forty-three hepatocellular carcinomas were not visible with CT fluoroscopy. A 22-gauge Chiba end-hole needle was inserted in the approximate location of a lesion estimated on the basis of anatomical landmarks demonstrated on both previous MR and CT images. We injected 3 ml of a mixture of nonionic contrast material and saline solution. Following the first injection, contrast solution filled the hepatic lesion in 29 of 43 cases. In 8 of 43 cases, contrast solution was distributed in the normal surrounding liver. In 7 of these 8 cases, repositioning allowed us to adjust the needle in the tumor. In the other 6 of 43 cases, contrast solution spread within capsule or pseudocapsule (pattern 3). In all 6 cases, repositioning allowed to adjust the needle in the tumor. This new technique allows an accurate localization of hepatic tumors that are poorly visible with CT fluoroscopy. (orig.)

Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

International Nuclear Information System (INIS)

Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

2012-01-01

Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

Malignant hepatic perivascular epithelioid cell tumor (PEComa)- Case report and a brief review

International Nuclear Information System (INIS)

Abhirup, B.; Kaushal, K.; Ganesh, N.; Sanket, M.

2015-01-01

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms which can arise from almost any location in the body. Diagnosing them pre-operatively is difficult as they mimic features of other hepatic neoplasms including hepatocellular carcinoma (HCC), fibrolamellar HCC, and focal nodular hyperplasia (FNH) among others. The unique feature of these tumors is the coexpression of muscle and melanocytic markers. These are identified immunohistochemically by the expression of Human Melanin Black-45 (HMB-45), Melan-A and Smooth Muscle Antigen (SMA) which are seen in the majority of tumors. The liver is uncommonly associated with a PEComa and the approach to a patient with hepatic PEComa is not well described. There is no consensus regarding the neo-adjuvant/adjuvant therapy in these patients. The natural history of this condition is not well documented making it an unpredictable disease. Here we have discussed a case and reviewed the literature concerning these rare tumors.

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

Directory of Open Access Journals (Sweden)

Valentin Lestelle

2015-10-01

Full Text Available We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

[A Case with Metastatic Huge Ovarian Tumor from Transverse Colon Cancer, Who Underwent Systemic Chemotherapy after Bilateral Oophorectomy and Right Hemi Colectomy].

Science.gov (United States)

Miyanari, Shun; Nagasaki, Toshiya; Minami, Hironori; Fukuoka, Hironori; Murahashi, Satoshi; Suzuki, Shinsuke; Ushigome, Hajime; Akiyoshi, Takashi; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi

2017-11-01

Metastatic ovarian tumors from colon cancer would be resistant to chemotherapy, and compromising quality of life(QOL) of these patients was caused by acute enlargement of the tumors. A 37-year-old woman with abdominal distension was diagnosed with transverse colon cancer, bilateral ovarian metastases, liver metastases, and peritoneal dissemination at prior hospital. Two courses of chemotherapy(FOLFOX)were administered, but metastaticovarian tumors enlarged. Chemotherapy was discontinued and she was referred to our institution. To achieve symptom relief, improving QOL, and to resume chemotherapy, we planned bilateral oophorectomy and primary tumor resection if other stenotic lesion was not present. As a result, we safely performed open bilateral oophorectomy and right hemi colectomy, and the patient discharged on postoperative day 11 without complications. Chemotherapy was resumed and continued for 7 months up to this time. Even though, curative resection could not be achieved, oophorectomy should be performed in patients with enlarged metastatic ovarian tumor from colon cancer, in spite of administration of chemotherapy.

Results of radiofrequency ablation of liver tumors: experience of 134 cases

Directory of Open Access Journals (Sweden)

Marcelo Augusto Fontenelle Ribeiro Junior

2008-12-01

Full Text Available Objective: To study radiofrequency ablation of primary and metastatic livertumors. Methods: The authors present a series of 134 cases, 63 femalesand 71 males with a mean age of 61.2 years, in whom radiofrequencyablation was used either by laparotomy or percutaneously to treat 203lesions. The group was composed of 51 cases of hepatocellular carcinoma,four cases of cholangiocarcinoma, and cases of hepatic metastases, asfollows: 64 of colorectal cancer, 6 of neuroendocrine tumors, 5 of breastcancer, 1 case of pancreas cancer, 1 of kidney cancer, 1 of endometrialcancer and 1 of leiomyosarcoma. Results: Procedure-associatedmorbidity/mortality was 24.8 and 3.7%, respectively. Recurrence wasobserved in 12.7% within a mean time of 10.5 months. Conclusions:Radiofrequency ablation is a safe procedure and can be used in patientswith impaired hepatic function. For metastatic diseases, it does notreplace surgery but it can be associated with other procedures, such assurgery and transarterial chemoembolization, or after recurrence, leadingto greater probability of remaining disease-free.

Pleiotropic function of ezrin in human metastatic melanomas.

Science.gov (United States)

Federici, Cristina; Brambilla, Daria; Lozupone, Francesco; Matarrese, Paola; de Milito, Angelo; Lugini, Luana; Iessi, Elisabetta; Cecchetti, Serena; Marino, Marialucia; Perdicchio, Maurizio; Logozzi, Mariantonia; Spada, Massimo; Malorni, Walter; Fais, Stefano

2009-06-15

The membrane cytoskeleton cross-linker, ezrin, has recently been depicted as a key regulator in the progression and metastasis of several pediatric tumors. Less defined appears the role of ezrin in human adult tumors, especially melanoma. We therefore addressed ezrin involvement in the metastatic phenotype of human adult metastatic melanoma cells. Our results show that cells resected from melanoma metastatic lesions of patients, display marked metastatic spreading capacity in SCID mice organs. Stable transfection of human melanoma cells with an ezrin deletion mutant comprising only 146 N-terminal aminoacids led to the abolishment of metastatic dissemination. In vitro experiments revealed ezrin direct molecular interactions with molecules related to metastatic functions such as CD44, merlin and Lamp-1, consistent with its participation to the formation of phagocitic vacuoles, vesicular sorting and migration capacities of melanoma cells. Moreover, the ezrin fragment capable of binding to CD44 was shorter than that previously reported, and transfection with the ezrin deletion mutant abrogated plasma membrane Lamp-1 recruitment. This study highlights key involvement of ezrin in a complex machinery, which allows metastatic cancer cells to migrate, invade and survive in very unfavorable conditions. Our in vivo and in vitro data reveal that ezrin is the hub of the metastatic behavior also in human adult tumors. Copyright 2008 UICC.

Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

Science.gov (United States)

Mercer, Kelly E; Pulliam, Casey F; Pedersen, Kim B; Hennings, Leah; Ronis, Martin Jj

2017-03-01

Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein

Contrast enhanced ultrasound in the evaluation and percutaneous treatment of hepatic and renal tumors

International Nuclear Information System (INIS)

Meloni, Maria Franca; Smolock, Amanda; Cantisani, Vito; Bezzi, Mario; D'Ambrosio, Ferdinando; Proiti, Maria; Lee, Fred; Aiani, Luca; Calliada, Fabrizio; Ferraioli, Giovanna

2015-01-01

Highlights: • Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney when surgery is not indicated. • Percutaneous ablation relies on imaging at every step of the process in order to detect, guide, and confirm complete tumor coagulation. • CEUS is a real-time dynamic imaging technique that plays an important role in the management of patients treated with ablation for malignant tumors. • This review focuses on the role of CEUS in the evaluation of patients undergoing percutaneous treatments for hepatic and renal tumors. - Abstract: Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney. Contrast enhanced ultrasound (CEUS) is a real-time dynamic imaging technique that plays an important role in the pre-, intra-, and post-procedural management of these patients. This review will focus on the role of CEUS in the evaluation of patients undergoing treatment with percutaneous ablation for hepatic or renal tumors

Imaging of bioluminescent LNCaP-luc-M6 tumors: a new animal model for the study of metastatic human prostate cancer.

Science.gov (United States)

Scatena, Caroline D; Hepner, Mischa A; Oei, Yoko A; Dusich, Joan M; Yu, Shang-Fan; Purchio, Tony; Contag, Pamela R; Jenkins, Darlene E

2004-05-15

Animal experiments examining hormone-sensitive metastatic prostate cancer using the human LNCaP cell line have been limited to endpoint analyses. To permit longitudinal studies, we generated a luciferase-expressing cell line and used bioluminescent imaging (BLI) to non-invasively monitor the in vivo growth of primary LNCaP tumors and metastasis. LNCaP.FGC cells were transfected to constitutively express firefly luciferase. LNCaP-luc-M6 cells were tested for bioluminescent signal intensity and hormone responsiveness in vitro. The cells were implanted in subcutaneous and orthotopic sites in SCID-bg mice and imaged over time. The LNCaP-luc-M6 cells formed subcutaneous and orthotopic tumors in SCID-bg mice, and nearly all tumor-bearing animals developed pulmonary metastases. Early detection and temporal growth of primary tumors and metastatic lesions was successfully monitored by BLI. The LNCaP-luc-M6 cell line is a bioluminescent, hormone-sensitive prostate cancer cell line applicable for BLI studies to non-invasively monitor subcutaneous and orthotopic prostate tumor growth and metastasis in vivo. Copyright 2004 Wiley-Liss, Inc.

Specific expression of the human voltage-gated proton channel Hv1 in highly metastatic breast cancer cells, promotes tumor progression and metastasis

International Nuclear Information System (INIS)

Wang, Yifan; Li, Shu Jie; Pan, Juncheng; Che, Yongzhe; Yin, Jian; Zhao, Qing

2011-01-01

Highlights: → Hv1 is specifically expressed in highly metastatic human breast tumor tissues. → Hv1 regulates breast cancer cytosolic pH. → Hv1 acidifies extracellular milieu. → Hv1 exacerbates the migratory ability of metastatic cells. -- Abstract: The newly discovered human voltage-gated proton channel Hv1 is essential for proton transfer, which contains a voltage sensor domain (VSD) without a pore domain. We report here for the first time that Hv1 is specifically expressed in the highly metastatic human breast tumor tissues, but not in poorly metastatic breast cancer tissues, detected by immunohistochemistry. Meanwhile, real-time RT-PCR and immunocytochemistry showed that the expression levels of Hv1 have significant differences among breast cancer cell lines, MCF-7, MDA-MB-231, MDA-MB-468, MDA-MB-453, T-47D and SK-BR-3, in which Hv1 is expressed at a high level in highly metastatic human breast cancer cell line MDA-MB-231, but at a very low level in poorly metastatic human breast cancer cell line MCF-7. Inhibition of Hv1 expression in the highly metastatic MDA-MB-231 cells by small interfering RNA (siRNA) significantly decreases the invasion and migration of the cells. The intracellular pH of MDA-MB-231 cells down-regulated Hv1 expression by siRNA is obviously decreased compared with MDA-MB-231 with the scrambled siRNA. The expression of matrix metalloproteinase-2 and gelatinase activity in MDA-MB-231 cells suppressed Hv1 by siRNA were reduced. Our results strongly suggest that Hv1 regulates breast cancer intracellular pH and exacerbates the migratory ability of metastatic cells.

Evaluation of radiological prognostic factors of hepatic metastases in patients with non-functional pancreatic neuroendocrine tumors

Energy Technology Data Exchange (ETDEWEB)

Denecke, Timm [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Baur, Alexander D.J., E-mail: alexander.baur@charite.de [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Ihm, Claudia; Steffen, Ingo G. [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Tischer, Elisabeth [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Arsenic, Ruza [Institut für Pathologie, Campus Charité Mitte, Charité - Universitätsmedizin Berlin (Germany); Pascher, Andreas [Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Wiedenmann, Bertram; Pavel, Marianne [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany)

2013-10-01

Purpose: There are different therapeutic options in non-functional well to moderately differentiated (G1 and G2) pancreatic neuroendocrine tumors (pNET) with unresectable hepatic metastases including systemic chemotherapy and novel molecular targeted therapies. Treatment with somatostatin analogs (SSA) as antiproliferative agents is optional. At initial diagnosis watchful waiting until tumor progression is a well-established approach. Goal of this study was to evaluate imaging features as potential prognostic factors predicting early tumor progression in order to select patients that might benefit from an earlier initiation of medical treatment. Patients and methods: In 44 patients we correlated tumor grade, chromogranin A (CgA) levels, treatment with SSA and imaging features of hepatic metastases on contrast-enhanced multiphase CT and MR imaging with time to tumor progression (TTP) according to RECIST 1.0. Results: In the total patient cohort none of the tested imaging features was found to be a statistically significant prognostic factor for TTP. Since treatment with SSA was associated with an increased TTP we also analyzed a subgroup of 30 patients not treated with SSA. In this subgroup of patients hypoenhancement of hepatic metastases during early contrast phases was found to be a negative prognostic factor for early tumor progression within 12 months (p = 0.039). The other evaluated parameters including hepatic tumor load, number of metastases, and presence of regressive morphological changes did not reveal significant results. Conclusion: Hypovascularization of liver metastases from G1 and G2 pNET reflected by hypoenhancement during the early contrast phases seems to be associated with early tumor progression. In patients with hypoenhancing metastases repeated biopsy for reassessment of grading of these metastases, and early initiation of therapy should be considered.

S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance

DEFF Research Database (Denmark)

Grum-Schwensen, Birgitte; Klingelhöfer, Jörg; Beck, Mette

2015-01-01

, decreased vessel density and inhibition of metastases. CONCLUSION: The S100A4 blocking antibody (6B12) reduces tumor growth and metastasis in a model of spontaneous breast cancer. The 6B12 antibody treatment inhibits T cell accumulation at the primary and pre-metastatic tumor sites. The 6B12 antibody acts...

Treatment of therapy-resistant perineal metastatic Crohn's disease after proctectomy using anti-tumor necrosis factor chimeric monoclonal antibody, cA2 - Report of two cases

NARCIS (Netherlands)

van Dullemen, HM; de Jong, E; Slors, F; Tytgat, GNJ; van Denventer, SJH

PURPOSE: Two young females with well-documented Crohn's disease and nonhealing perineal wounds following proctectomy compatible with "metastatic Crohn's disease" are described, We hypothesized that metastatic Crohn's disease would be a tumor necrosis factor-dependent inflammatory-reaction and have

Budget impact of somatostatin analogs as treatment for metastatic gastroenteropancreatic neuroendocrine tumors in US hospitals

Directory of Open Access Journals (Sweden)

Ortendahl JD

2017-08-01

Full Text Available Jesse D Ortendahl,1 Sonia J Pulgar,2 Beloo Mirakhur,3 David Cox,3 Tanya GK Bentley,1 Alexandria T Phan4 1Health Economics, Partnership for Health, LLC, Beverly Hills, CA, USA; 2Health Economics and Outcomes Research, Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 3Medical Affairs, Oncology, Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 4GI Medical Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA Objective: With the introduction of new therapies, hospitals have to plan spending limited resources in a cost-effective manner. To assist in identifying the optimal treatment for patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors, budget impact modeling was used to estimate the financial implications of adoption and diffusion of somatostatin analogs (SSAs. Patients and methods: A hypothetical cohort of 500 gastroenteropancreatic neuroendocrine tumor patients was assessed in an economic model, with the proportion with metastatic disease treated with an SSA estimated using published data. Drug acquisition, preparation, and administration costs were based on national pricing databases and published literature. Octreotide dosing was based on published estimates of real-world data, whereas for lanreotide, real-world dosing was unavailable and we therefore used the highest indicated dosing. Alternative scenarios reflecting the proportion of patients receiving lanreotide or octreotide were considered to estimate the incremental budget impact to the hospital. Results: In the base case, 313 of the initial 500 gastroenteropancreatic neuroendocrine tumor patients were treated with an SSA. The model-predicted per-patient cost was US$83,473 for lanreotide and US$89,673 for octreotide. With a hypothetical increase in lanreotide utilization from 5% to 30% of this population, the annual model-projected hospital costs decreased by US$488,615. When varying the inputs in one-way sensitivity

Disseminated breast cancer cells acquire a highly malignant and aggressive metastatic phenotype during metastatic latency in the bone.

Directory of Open Access Journals (Sweden)

Carolyn G Marsden

Full Text Available BACKGROUND: Disseminated tumor cells (DTCs in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorigenicity and metastatic potential of dormant disseminated breast cancer cells (prior to activation in the bone marrow. METHODOLOGY/PRINCIPAL FINDINGS: Total bone marrow, isolated from mice previously injected with tumorspheres into the mammary fat pad, was injected into the mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were analyzed by H+E staining to detect metastases. The injection of bone marrow isolated from mice previously injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-injection. However, the injection of bone marrow isolated from non-injected mice did not result in tumor formation in the mammary fat pad. The DTC-derived tumors exhibited accelerated development of metastatic lesions within the lung, liver and kidney. The resultant tumors and the majority of metastatic lesions within the lung and liver exhibited a mesenchymal-like phenotype. CONCLUSIONS/SIGNIFICANCE: Dormant DTCs within the bone marrow are highly malignant upon injection into the mammary fat pad, with the accelerated development of metastatic lesions within the lung, liver and kidney. These results suggest the acquisition of a more aggressive phenotype of DTCs during

Follow-up of hepatic and peritoneal metastases of gastrointestinal tumors (GIST) under Imatinib therapy requires different criteria of radiological evaluation (size is not everything!!!)

International Nuclear Information System (INIS)

Mabille, Mylene; Vanel, Daniel; Albiter, Marcela; Le Cesne, Axel; Bonvalot, Sylvie; Le Pechoux, Cecile; Terrier, Philippe; Shapeero, Lorraine G.; Dromain, Clarisse

2009-01-01

Purpose: To define computed tomography (CT) criteria for evaluating the response of patients with gastrointestinal stromal tumors (GIST) who are receiving Imatinib (tyrosine-kinase inhibitor therapy). Materials and methods: This prospective CT study evaluated 107 consecutive patients with advanced metastatic GIST treated with Imatinib. Results: Seventy patients had total or partial cystic-like transformation of hepatic and/or peritoneal metastases. These pseudocysts remained unchanged in size or stable in size on successive CT examinations (stable disease according to RECIST criteria). Forty-six patients developed metastases, 17 patients showed increasing parietal thickness and 29 patients with peripheral enhancing nodules. These CT changes represented local recurrence consistent with GIST resistance to Imatinib treatment. WHO or RECIST criteria did not provide a reliable evaluation of disease evolution or recurrence. Development of new enhancement of lesions (parietal thickness or nodule) was the only reliable criterion. Conclusion: The development of peripheral thickening or enhancing nodules within cystic-like metastatic lesions, even without any change in size, represented progressive GIST under Imatinib, growing in a short time and should alert the clinician for the possible need for a change in therapy

Hepatoduodenal lymph node metastasis mimicking Klatskin tumor in a patient with sigmoid colon mucinous cancer

Directory of Open Access Journals (Sweden)

Hovhannes Vardevanyan, PhD

2017-09-01

Full Text Available We report a case of a 48-year-old female patient, who presented with abdominal pain, jaundice, and lack of appetite. Ultrasound showed intrahepatic biliary dilatation with retroperitoneal lymphadenopathy. Further magnetic resonance cholangiopancreatography detected Klatskin tumor. Computed tomography (CT confirmed the Klatskin tumor with liver metastases and retroperitoneal lymphadenopathy. Biopsy from the hepatic lesion identified mucinous adenocarcinoma, likely originating from bile ducts. Endoscopic retrograde cholangiopancreatography was performed 3 times with stents placed in the left and right hepatic bile ducts. Later the patient had hematochezia and was referred to colonoscopy. Tubulovillous adenoma with dysplasia was diagnosed with signs of in situ cancer. Preoperative CT was done for further staging: new pulmonary metastases were discovered. Sigmoid colon was resected. Histopathology verified a poorly differentiated mucinous adenocarcinoma within the tubulovillous adenoma. Intraoperative biopsies of porta hepatis mass resembled metastatic lymph nodes in hepatoduodenal ligament, mimicking Klatskin tumor. Retrospective analysis of CT data demonstrated presence of sigmoid colon tumor.

Primary Neuroendocrine Tumor of the Left Hepatic Duct: A Case Report with Review of the Literature

Directory of Open Access Journals (Sweden)

Ajay H. Bhandarwar

2012-01-01

Full Text Available Primary Biliary Tract Neuroendocrine tumors (NET are extremely rare tumors with only 77 cases been reported in the literature till now. We describe a case of a left hepatic duct NET and review the literature for this rare malignancy. To the best of our knowledge the present case is the first reported case of a left hepatic duct NET in the literature. In spite of availability of advanced diagnostic tools like Computerized Tomography (CT Scan and Endoscopic Retrograde Cholangio Pancreaticography (ERCP a definitive diagnosis of these tumors is possible only after an accurate histopathologic diagnosis of operative specimens with immunohistochemistry and electron microscopy. Though surgical excision remains the gold standard treatment for such tumors, patients with unresectable tumors have good survival with newer biologic agents like Octreotride.

Acute lymphoblastic leukemia mimicking Wilms tumor at presentation.

Science.gov (United States)

Singh, Amitabh; Mandal, Anirban; Guru, Vijay; Seth, Rachna

2016-09-01

Acute lymphoblastic leukemia (ALL), the commonest malignancy of childhood, is known to manifest with a myriad of atypical presentations. Nephromegaly is a rare presentation of childhood ALL with hepatic mass being even rarer. We present a 3 year-old child with unilateral renal mass and hepatic mass lesion with normal blood counts, initially suspected to have metastatic Wilms tumor based on clinical, radiological and WT1 positivity on immunocytochemistry of renal mass. He was later diagnosed as ALL with peripheral blood flowcytometry and bone marrow examination. Renomegaly at presentation of acute leukemia is not necessarily due to leukemic infiltration and rarely leads to renal impairment. The radiological differential of such a renal mass includes both benign and malignant entities including metastasis. Over-expression of WT1 mRNA has been found in a number of solid tumors and hematological malignancies and is far from being diagnostic of Wilms tumor. Again, a small number of children with acute leukemia may have a deceptively normal complete blood count at presentation. Though, initial all (clinical, radiological, hematological, and immunocytological) parameters pointed towards a diagnosis of Wilms tumor in our case, the subsequent development of thrombocytopenia and lymphocytic leukocytosis prompted further investigation and final diagnosis of ALL. WT1 positivity is a known phenomenon in childhood ALL and undifferentiated lymphoblasts may be positive for WT1 and negative for Leucocyte common antigen. Acute leukemia with renal and hepatic mass with normal blood counts at presentation is a diagnostic challenge.

Biological impact of geometric uncertainties: what margin is needed for intra-hepatic tumors?

International Nuclear Information System (INIS)

Kuo, Hsiang-Chi; Liu, Wen-Shan; Wu, Andrew; Mah, Dennis; Chuang, Keh-Shih; Hong, Linda; Yaparpalvi, Ravi; Guha, Chandan; Kalnicki, Shalom

2010-01-01

To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages. Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses (EUD) for various survival fractions at 2 Gy (SF 2 ). There was no significant difference in the biological impact between the full motion margin and the 70% motion margin. Also, there was no significant difference between different tumor cell types. When the margin for motion was eliminated, the difference of the biological impact was significant among different cell types due to geometric uncertainties. Elimination of the motion margin requires dose escalation to compensate for the biological dose reduction due to the geometric misses during treatment. Both patient-based margins of full motion and of 70% motion are sufficient to prevent serious dosimetric error. Clinical implementation of margin reduction should consider the tumor sensitivity to radiation

Gastric injury from 90Y to left hepatic lobe tumors adjacent to the stomach: fact or fiction?

International Nuclear Information System (INIS)

Gates, Vanessa L.; Hickey, Ryan; Marshall, Karen; Williams, Melissa; Salzig, Krystina; Lewandowski, Robert J.; Salem, Riad

2015-01-01

Radioembolization with 90 Y microspheres is a locoregional radiation therapy for unresectable hepatic neoplasm. Non-target delivery of 90 Y microspheres resulting in gastrointestinal (GI) symptoms is a recognized complication; there is minimal knowledge regarding the radiation effect to the gastric wall from left hepatic lobe 90 Y treatments. Our aim was to study the incidence of GI complications when the target tissue (hepatic parenchyma ± tumor) is in close proximity to the gastric wall. We hypothesized that liver (tumor) to stomach proximity does not correlate with increased toxicity. Between November 2011 and September 2013, we studied all patients who underwent left lobe radioembolization with 90 Y glass microspheres. With Institutional Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these patients, identifying a subset of patients with the left hepatic lobe <1 cm from the gastric wall. Patients were seen in clinic 1 month posttreatment and subsequently at 3-month intervals. Short- and long-term gastric adverse events were tabulated. Ninety-seven patients successfully underwent left hepatic lobe 90 Y microsphere radioembolization in which the average distance from the liver to the stomach wall was 1.0 ± 2.8 mm. The average dose for patients who received radioembolization to the left hepatic lobe was 109 ± 57 Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose for patients who received radioembolization to the left hepatic lobe with tumor within 1 cm of the gastric wall was 121 ± 41 Gy. There were no reportable or recordable medical events. Of the patients, 34 % reported abdominal pain that was grade 1-2; 65 % of the patients reported no abdominal pain. None of the 97 patients developed a clinically evident GI ulcer. Patients with left lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic radiation effects following radioembolization with glass microspheres. (orig.)

MRI diagnosis and preoperative evaluation for hepatic hilar tumor

International Nuclear Information System (INIS)

Liu Yulin; Kong xiangquan; Xu Haibo; Xiao Xuehong; Liu Dingxi; Peng Zhenjun

2004-01-01

Objective: To investigate the value of the all-in-one MR scanning in the diagnosis and preoperative evaluation of hepatic hilar tumor. Methods: Forty-two cases of hepatic hilar tumors were examined with a 1.5 T superconductive MR system, including hepatocellular carcinoma (HCC, n=12), hilar cholangiocarcinoma (HC, n=22), and hilar metastasis (n=8). Besides the precontrast MRI and MRCP, all cases underwent consecutive dynamic contrast-enhanced MR scanning. The whole liver dynamic contrast-enhanced MR was performed with the first bolus injection of Gd-DTPA (10 ml), and 15 minutes later, 3D DCE MRA was performed with additional injection of Gd-DTPA (15-20 ml) (0.15-0.20 mmol/kg). The contrast time-signal curve of liver and tumor was drawn, and arterial and portal venous phase images were reconstructed with MIP. MR appearances were compared with surgical findings and pathology. Results: Consecutive DCE scanning was successfully performed in all cases. The contrast time-signal curve of HCC showed type I and II (10/12, 83.3%), and the curve of HC showed type III and IV (21/22, 95.4%), whereas the curve of metastasis was various. The difference of tumor peak transit time (PT) between HCC group and HC group was significant (P<0.05). The vascular invasion in HCC group appeared as arterial-portal vein fistula (2/12, 16.7%), portal vein infiltration (3/24, 12.5%), and occlusion by tumor thrombosis (4/24, 16.7%). However, the vascular invasion in HC group showed spiral artery (5/22, 22.7%), portal vein infiltration (5/44, 11.4%), portal vein central narrowing (8/44, 18.2%) and occlusion (11/44, 25.0%). All metastasis had no vascular invasion expect one gall bladder carcinoma with right portal vein infiltration. The accuracy of preoperative evaluation with MRI in HCC group and HC group was 83.3% (10/12) and 86.4% (19/22), respectively. The accuracy of preoperative evaluation in all hilar tumors was 78.6% (33/42). Conclusion: Consecutive DCE was a safe and useful technique in MR

Evaluation of hepatic hemangioma by Tc-99 m red blood cell hepatic blood pool scan

International Nuclear Information System (INIS)

Sohn, Myung Hee

2005-01-01

Hemangioma is the most common benign tumor of the liver, with a prevalence estimated as high as 7%. Tc-99m red blood cell (RBC) hepatic blood pool scan with single photon emission computed tomography (SPECT) imaging is extremely useful for the confirmation or exclusion of hepatic hemangiomas. The classic finding of absent or decreased perfusion and increased blood pooling ('perfusion/blood pool mismatch') is the key diagnostic element in the diagnosis of hemangiomas. The combination of early arterial flow and delayed blood pooling ('perfusion/blood pool match') is shown uncommonly. In giant hemangioma, filling with radioactivity appears first in the periphery, with progressive central fill-in on sequential RBC blood pool scan. However, the reverse filling pattern, which begins first in the center with progressive peripheral filling, is also rarely seen. Studies with false-positive blood pooling have been reported infrequently in nonhemangiomas, including hemangiosarcoma, hepatocellular carcinoma, hepatic adenoma, and metastatic carcinomas (adenocarcinma of the colon, small cell carcinoma of the lung, neruroendocrine carcinoma). False-negative results have been also reported rarely except for small hemagniomas that are below the limits of spatial resolution of gamma camera

Radiofrequency ablation of hepatic metastasis: Results of treatment in forty patients

Directory of Open Access Journals (Sweden)

Rath G

2008-01-01

Full Text Available Aim: To evaluate the local control of hepatic metastasis with radiofrequency ablation treatment. Materials and Methods: We did a retrospective analysis in 40 patients treated with radiofrequency ablation for hepatic metastasis. The tumors ablated included up to two metastatic liver lesions, with primaries in breast, gastrointestinal tract, cervix, etc. Radiofrequency ablation was performed under general anesthesia in all cases, using ultrasound guidance. Radionics Cool-Tip RF System was used to deliver the treatment. Results: The median age of patients treated was 49 years. There were 13 female and 27 male patients. The median tumor size ablated was 1.5 cm (0.75-4.0 cm. A total of 52 radiofrequency ablation cycles were delivered. Successful ablation was achieved in all patients with hepatic metastasis less than 3 cm in size. Pain was the most common complication seen (75%. One patients developed skin burns. At 2-year follow-up 7.5% of patients had locally recurrent disease. Conclusions: Radiofrequency ablation is a minimally invasive treatment modality. It can be useful in a select group of patients with solitary liver metastasis of less than 3 cm size.

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3). Combination effect on the metastatic tumors

Energy Technology Data Exchange (ETDEWEB)

Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-03-01

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF/sub 1/ mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.

Peritumoral edema of meningiomas and metastatic brain tumors: differences in diffusion characteristics evaluated with diffusion-tensor MR imaging

International Nuclear Information System (INIS)

Toh, Cheng-Hong; Wong, Alex M.-C; Wong, Ho-Fai; Wan, Yung-Liang; Wei, Kuo-Chen; Ng, Shu-Hang

2007-01-01

We prospectively compared the fractional anisotropy (FA) and mean diffusivity (MD) of the peritumoral edema of meningiomas and metastatic brain tumors with diffusion-tensor magnetic resonance (MR) imaging. The study protocol was approved by the local ethics committee, and written informed consent was obtained. Preoperative diffusion-tensor MR imaging was performed in 15 patients with meningiomas and 11 patients with metastatic brain tumors. Regions of interest (ROI) were placed in the peritumoral edema and normal-appearing white matter (NAWM) of the contralateral hemisphere to measure the FA and MD. The FA and MD ratios were calculated for each ROI in relation to the NAWM of the contralateral hemisphere. Changes in peritumoral MD and FA, in terms of primary values and ratios, were compared using a two-sample t-test; P -3 mm 2 /s) of the peritumoral edema for metastases and meningiomas, respectively, were 0.902 ± 0.057 and 0.820 ± 0.094, the mean MD ratios were 220.3 ± 22.6 and 193.1 ± 23.4, the mean FA values were 0.146 ± 0.026 and 0.199 ± 0.052, and the mean FA ratios were 32.3 ± 5.9 and 46.0 ± 12.1. All the values were significantly different between metastases and meningiomas (MD values P 0.016, MD ratios P = 0.006, FA values P = 0.005, FA ratios P = 0.002). The peritumoral edema of metastatic brain tumors and meningiomas show different MD and FA on diffusion-tensor MR imaging. (orig.)

Peritumoral edema of meningiomas and metastatic brain tumors: differences in diffusion characteristics evaluated with diffusion-tensor MR imaging

Energy Technology Data Exchange (ETDEWEB)

Toh, Cheng-Hong; Wong, Alex M.-C; Wong, Ho-Fai; Wan, Yung-Liang [Chang Gung Memorial Hospital, Department of Medical Imaging and Intervention, Tao-Yuan (China); Chang Gung University, School of Medicine and Medical Technology, Tao-Yuan (China); Wei, Kuo-Chen [Chang Gung Memorial Hospital, Department of Neurosurgery, Tao-Yuan (China); Chang Gung University, School of Medicine and Medical Technology, Tao-Yuan (China); Ng, Shu-Hang [Chang Gung Memorial Hospital, Department of Medical Imaging and Intervention, Tao-Yuan (China); Chang Gung University, School of Medicine and Medical Technology, Tao-Yuan (China); Chang Gung Memorial Hospital, Molecular Image Center, Tao-Yuan (China)

2007-06-15

We prospectively compared the fractional anisotropy (FA) and mean diffusivity (MD) of the peritumoral edema of meningiomas and metastatic brain tumors with diffusion-tensor magnetic resonance (MR) imaging. The study protocol was approved by the local ethics committee, and written informed consent was obtained. Preoperative diffusion-tensor MR imaging was performed in 15 patients with meningiomas and 11 patients with metastatic brain tumors. Regions of interest (ROI) were placed in the peritumoral edema and normal-appearing white matter (NAWM) of the contralateral hemisphere to measure the FA and MD. The FA and MD ratios were calculated for each ROI in relation to the NAWM of the contralateral hemisphere. Changes in peritumoral MD and FA, in terms of primary values and ratios, were compared using a two-sample t-test; P < 0.05 was taken as indicating statistical significance. The mean MD values (x 10{sup -3} mm{sup 2}/s) of the peritumoral edema for metastases and meningiomas, respectively, were 0.902 {+-} 0.057 and 0.820 {+-} 0.094, the mean MD ratios were 220.3 {+-} 22.6 and 193.1 {+-} 23.4, the mean FA values were 0.146 {+-} 0.026 and 0.199 {+-} 0.052, and the mean FA ratios were 32.3 {+-} 5.9 and 46.0 {+-} 12.1. All the values were significantly different between metastases and meningiomas (MD values P = 0.016, MD ratios P = 0.006, FA values P = 0.005, FA ratios P = 0.002). The peritumoral edema of metastatic brain tumors and meningiomas show different MD and FA on diffusion-tensor MR imaging. (orig.)

Super bone scans on bone scintigraphy in patients with metastatic bone tumor

International Nuclear Information System (INIS)

Morita, Koichi; Fukunaga, Masao; Otsuka, Nobuaki

1988-01-01

Eight patients with malignant tumor (3 with gastric cancer, 4 with prostatic cancer, 1 with transitional cell carcinoma), which showed diffusely increased uptake of 99m Tc labelled phosphorous compound in axial skeleton (''Super Bone Scan'') on bone scintigraphy were clinically studied. No relationship with its histological type of the tumor was recognized. All cases revealed extremely high serum ALP concentration, which might reflect increased osteoblastic activity. Furthermore, on bone roentgenograms all cases showed predominantly osteosclerotic change in the metastatic bones, while some did locally osteolytic change. In three cases with gastric cancer, although they had diffuse skeletal metastases, two had no evidence of liver metastases. Thus, it seemed that clinical study of patients with ''Super Bone Scan'' was interesting to evaluate the mechanism of accumulation of 99m Tc labelled phosphorous compound to bone and bone metabolism, and the pathophysiology in the pathway of bone metastases. (author)

Multi-course PDT of malignant tumors: the influence on primary tumor, metastatic spreading and homeostasis of cancer patients

Science.gov (United States)

Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Filonenko, E. V.; Sukhin, Garry M.; Nemtsova, E. R.; Belous, T. A.; Zharkova, Natalia N.

1996-12-01

The first clinical trials of photodynamic therapy (PDT) of cancer with two photosensitizers, PHOTOHEME and PHOTOSENS, were started in P.A. Hertzen Research Oncological Institute (Moscow, Russia) in 1992 and 1994. Up to now, 208 patients with primary, recurrent and metastatic malignant tumors (469) of skin (34 patients/185 tumors), breast cancer (24/101), head and neck (30/31), trachea and bronchus (31/42), esophagus (35/35), stomach (31/32), rectum (4/4), vagina and uterine cervix (7/8) and bladder (12/31) have been treated by PDT. One-hundred-thirty patients were injected with PHOTOHEME, 64 patients were injected with PHOTOSENS, 14 patients were injected with PHOTOHEME and PHOTOSENS. Totally, 302 courses of treatment were performed: 155 patients had one course and 53 patients were subjected to two to nine PDT sources with intervals from 1 to 18 months. A therapeutic effect of a one-course and multi- course PDT of malignant tumors (respiratory, digestive and urogenital systems) was evaluated clinically, histologically, roentgenologically, sonographically and endoscopically. The biochemical, hematological and immunological investigations were performed for all the patients in dynamics. Results of our study showed that a multi-course PDT method seems to be perspective in treatment of malignant tumors of basic localizations.

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

Science.gov (United States)

Shmelkov, Sergey V.; Butler, Jason M.; Hooper, Andrea T.; Hormigo, Adilia; Kushner, Jared; Milde, Till; St. Clair, Ryan; Baljevic, Muhamed; White, Ian; Jin, David K.; Chadburn, Amy; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; D’Angelica, Michael; Kemeny, Nancy; Lyden, David; Rafii, Shahin

2008-01-01

Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic

CT-guided radiofrequency tumor ablation in children

International Nuclear Information System (INIS)

Botsa, Evanthia; Poulou, Loukia S.; Koundouraki, Antonia; Thanos, Loukas; Koutsogiannis, Ioannis; Ziakas, Panayiotis D.; Alexopoulou, Efthimia

2014-01-01

Image-guided radiofrequency ablation is a well-accepted technique of interventional oncology in adults. To evaluate the efficacy and safety of CT-guided radiofrequency ablation as a minimally invasive treatment for metastatic neoplasms in children. A total of 15 radiofrequency ablation sessions were performed in 12 children and young adults (median age 9.5; range 5-18 years) with metastatic malignancies. Seven children and young adults had secondary hepatic lesions, three had pulmonary and two had bone lesions. Radiofrequency ablation was performed under conscious sedation. The median lesion size was 1.7 cm (range 1.3-2.8 cm). The median time for ablation was 8 min (range 7-10 min). Radiofrequency procedures were technically successful in all tumors. Postablation imaging immediately after, and 1 month and 3 months after radiofrequency ablation showed total necrosis in all patients. At 6-month follow-up, three patients (all with lesion size >2 cm) had local recurrence and underwent a second radiofrequency ablation session. At 2-year follow-up no patient had recurrence of the treated tumor. Post-ablation syndrome occurred in four children. No major complication occurred. CT-guided radiofrequency tumor ablation was safe and efficient for palliative treatment in our cohort of patients. (orig.)

CT-guided radiofrequency tumor ablation in children

Energy Technology Data Exchange (ETDEWEB)

Botsa, Evanthia [National and Kapodistrian University of Athens, First Pediatric Clinic, Agia Sofia Children' s Hospital, Athens (Greece); Poulou, Loukia S.; Koundouraki, Antonia; Thanos, Loukas [Sotiria General Hospital for Chest Diseases, Department of Medical Imaging and Interventional Radiology, Athens (Greece); Koutsogiannis, Ioannis [General Military Hospital NIMTS, Department of Medical Imaging, Athens (Greece); Ziakas, Panayiotis D. [Warren Alpert Medical School of Brown University Rhode Island Hospital, Division of Infectious Diseases, Providence, RI (United States); Alexopoulou, Efthimia [Attikon University Hospital, Second Department of Radiology, Athens University School of Medicine, Athens (Greece)

2014-11-15

Image-guided radiofrequency ablation is a well-accepted technique of interventional oncology in adults. To evaluate the efficacy and safety of CT-guided radiofrequency ablation as a minimally invasive treatment for metastatic neoplasms in children. A total of 15 radiofrequency ablation sessions were performed in 12 children and young adults (median age 9.5; range 5-18 years) with metastatic malignancies. Seven children and young adults had secondary hepatic lesions, three had pulmonary and two had bone lesions. Radiofrequency ablation was performed under conscious sedation. The median lesion size was 1.7 cm (range 1.3-2.8 cm). The median time for ablation was 8 min (range 7-10 min). Radiofrequency procedures were technically successful in all tumors. Postablation imaging immediately after, and 1 month and 3 months after radiofrequency ablation showed total necrosis in all patients. At 6-month follow-up, three patients (all with lesion size >2 cm) had local recurrence and underwent a second radiofrequency ablation session. At 2-year follow-up no patient had recurrence of the treated tumor. Post-ablation syndrome occurred in four children. No major complication occurred. CT-guided radiofrequency tumor ablation was safe and efficient for palliative treatment in our cohort of patients. (orig.)

CHARACTERISTICS OF CLINICAL COURSE OF METASTATIC AND PRIMARY OVARIAN TUMORS IN COLON CANCER

Directory of Open Access Journals (Sweden)

I. A. Dzhanyan

2015-01-01

Full Text Available The aim of this study was to investigate clinical pecuiliarities of ovarian tumors in colon cancer patients and determination of complex diagnostic methods.Subject and methods. Russian N.N.  Blokhin Cancer Research Center archives were used for retrospective study, patients, who underwent treatment during 1989–2013  were included. Colon cancer patients with ovarian metastases and with synchronous or metachronous tumors were included.Results. 141 patients were included: 91 patients had colon cancer with ovarian metastases (group 1 and 50 patients had synchronous or metachronous ovarian tumours (group 2. Ovarian tumors were diagnosed during the 1 year in 74 (81.3 % patients in group 1 and in 23 (46 % in group 2. Patients in group 2 less frequently had children (9 (18.0 % vs 5 (5.5 + 2.3 %, р < 0.05, family history of cancer (3 (6 % vs 16 (17.6 %, р < 0.05 and concomitant diseases. Median CA 125 level in group 1 was 64.96 ng/ml and 180 ng/ml in group 2. Ovarian tumors had solid and cystic structure during US examination in 66 (73 % patients in group 1 and 31 (62 % patients in group 2 had solid ovarian tumors on US examination.Conclusions. The differential diagnostics of primary and metastatic ovarian tumors must include CEA, CA 19–9 and CA 125 serum levels and pelvic US.

Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

Science.gov (United States)

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-03-01

We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ultrasonic diagnosis of hepatic metastases in patients with stomach cancer and colon cancer

International Nuclear Information System (INIS)

Kye, Jong Sik; Lim, Jae Hoon; Ko, Young Tae; Ahn, Chi Yul

1987-01-01

To assess the value of hepatic ultrasound in cancer patients, a prospective evaluation was performed by comparing the preoperative ultrasound report and surgeon's diagnosis at the time of operation in 86 patients with stomach cancer and 26 patients with colon cancer. In a total of 112 patients considered to have a metastasis free liver on ultrasound scanning 10 patients were turned out to have had hepatic metastasis at the time of laparotomy. Among these, 4 patients had miliary metastasis, 4 patients had nodular metastasis at the dome of the right hepatic lobe, and 2 patients had surface metastasis or direct invasion from the primary tumor. These observations suggest that false negative preoperative hepatic ultrasound scanning is 9% had this is considered due to small size of the metastatic lesions, and lesions roundabout the dome of the right hepatic lobe or surface metastasis. Thus one should keep in mind the possibility of miliary metastasis in cancer patient was has coarse hepatic echotexture. In addition, the hepatic dome as well as hepatic surfaces should be searched carefully as the lesions in these areas tend to be easily neglected by ultrasound

The effect of pre-vertebroplasty tumor ablation using laser-induced thermotherapy on biomechanical stability and cement fill in the metastatic spine

OpenAIRE

Ahn, Henry; Mousavi, Payam; Chin, Lee; Roth, Sandra; Finkelstein, Joel; Vitken, Alex; Whyne, Cari

2007-01-01

A biomechanical study comparing simulated lytic vertebral metastases treated with laser-induced thermotherapy (LITT) and vertebroplasty versus vertebroplasty alone. To investigate the effect of tumor ablation using LITT prior to vertebroplasty on biomechanical stability and cement fill patterns in a standardized model of spinal metastatic disease. Vertebroplasty in the metastatic spine is aimed at reducing pain, but is associated with risk of cement extravasation in up to 10%. Six pairs of fr...

Plasma methoxytyramine: A novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumor size, location and SDHB mutation status

Science.gov (United States)

Eisenhofer, Graeme; Lenders, Jacques W.M.; Siegert, Gabriele; Bornstein, Stefan R.; Friberg, Peter; Milosevic, Dragana; Mannelli, Massimo; Linehan, W. Marston; Adams, Karen; Timmers, Henri J.; Pacak, Karel

2012-01-01

Summary Background There are currently no reliable biomarkers for malignant pheochromocytomas and paragangliomas (PPGLs). This study examined whether measurements of catecholamines and their metabolites might offer utility for this purpose. Methods Subjects included 365 patients with PPGLs, including 105 with metastases, and a reference population of 846 without the tumor. Eighteen catecholamine-related analytes were examined in relation to tumor location, size and mutations of succinate dehydrogenase subunit B (SDHB). Results Receiver-operating characteristic curves indicated that plasma methoxytyramine, the O-methylated metabolite of dopamine, provided the most accurate biomarker for discriminating patients with and without metastases. Plasma methoxytyramine was 4.7-fold higher in patients with than without metastases, a difference independent of tumor burden and the associated 1.6- to 1.8-fold higher concentrations of norepinephrine and normetanephrine. Increased plasma methoxytyramine was associated with SDHB mutations and extra-adrenal disease, but was also present in patients without SDHB mutations and metastases or those with metastases secondary to adrenal tumors. High risk of malignancy associated with SDHB mutations reflected large size and extra-adrenal locations of tumors, both independent predictors of metastatic disease. A plasma methoxytyramine above 0.2 nmol/L or a tumor diameter above 5 cm indicated increased likelihood of metastatic spread, particularly when associated with an extra-adrenal location. Interpretation Plasma methoxytyramine is a novel biomarker for metastatic PPGLs that together with SDHB mutation status, tumor size and location provide useful information to assess the likelihood of malignancy and manage affected patients. PMID:22036874

Hepatic vein tumor thrombus as a risk factor for excessive pulmonary deposition of microspheres during TheraSphere therapy for unresectable hepatocellular carcinoma.

Science.gov (United States)

Fleming, Chad J; Andrews, James C; Wiseman, Gregory A; Gansen, Denise N; Roberts, Lewis R

2009-11-01

To evaluate the impact of identifiable hepatic vein tumor thrombus on the ability to safely deliver TheraSphere (yttrium 90-containing glass microspheres) for the treatment of hepatocellular carcinoma (HCC). A retrospective review was performed of 87 patients (71 men, 16 women; mean age, 64.5 years; age range, 25-83 y) referred for TheraSphere therapy for HCC during a 2-year period between April 2005 and May 2007. Evaluation included contrast-enhanced computed tomography or magnetic resonance imaging, selective mesenteric angiography, and radionuclide perfusion scintigraphy to measure the arteriovenous shunting through the tumor. Of the 87 patients, 83 underwent angiography and perfusion scintigraphy; 53 were ultimately treated with 65 glass microsphere infusions. Twelve of 83 were identified as having tumor thrombus in a hepatic vein or extending into the inferior vena cava. The mean lung shunt for the patients with hepatic vein tumor thrombus was 30% (range, 11%-60%), compared with 8.2% (range, 3%-23%) for patients without identifiable tumor thrombus. Two of the 12 patients were treated with reduced doses of glass microspheres, and the remaining 10 were offered alternative therapies. The presence of hepatic vein tumor thrombus is a risk factor for an increased lung shunt that may prohibit delivery of a therapeutic dose of TheraSphere to hepatic tumor.

Polytomous diagnosis of ovarian tumors as benign, borderline, primary invasive or metastatic: development and validation of standard and kernel-based risk prediction models

Directory of Open Access Journals (Sweden)

Testa Antonia C

2010-10-01

Full Text Available Abstract Background Hitherto, risk prediction models for preoperative ultrasound-based diagnosis of ovarian tumors were dichotomous (benign versus malignant. We develop and validate polytomous models (models that predict more than two events to diagnose ovarian tumors as benign, borderline, primary invasive or metastatic invasive. The main focus is on how different types of models perform and compare. Methods A multi-center dataset containing 1066 women was used for model development and internal validation, whilst another multi-center dataset of 1938 women was used for temporal and external validation. Models were based on standard logistic regression and on penalized kernel-based algorithms (least squares support vector machines and kernel logistic regression. We used true polytomous models as well as combinations of dichotomous models based on the 'pairwise coupling' technique to produce polytomous risk estimates. Careful variable selection was performed, based largely on cross-validated c-index estimates. Model performance was assessed with the dichotomous c-index (i.e. the area under the ROC curve and a polytomous extension, and with calibration graphs. Results For all models, between 9 and 11 predictors were selected. Internal validation was successful with polytomous c-indexes between 0.64 and 0.69. For the best model dichotomous c-indexes were between 0.73 (primary invasive vs metastatic and 0.96 (borderline vs metastatic. On temporal and external validation, overall discrimination performance was good with polytomous c-indexes between 0.57 and 0.64. However, discrimination between primary and metastatic invasive tumors decreased to near random levels. Standard logistic regression performed well in comparison with advanced algorithms, and combining dichotomous models performed well in comparison with true polytomous models. The best model was a combination of dichotomous logistic regression models. This model is available online

Scan-guided fine needle aspiration biopsy in malignant hepatic disease

International Nuclear Information System (INIS)

Johansen, P.; Svendsen, K.N.

1978-01-01

The method of scan-guided fine needle aspiration biopsy of the liver is described, and the diagnostic value of this combined method in the diagnosis of malignant hepatic disease is evaluated in 83 confirmed cases, showing a specificity of 100% and a sensitivity of 94%. The combined method is compared to liver scanning alone and to Menghini biopsy. Different methods for the diagnosis of malignant hepatic disease are discussed, and it is concluded that scan-guided fine needle aspiration biopsy has a diagnostic value only obtainable otherwise by a combination of liver scanning and biopsy during laparoscopy. Cytologic features in the two most common tumor types in this study, i.e., metastatic colonic adenocarcinoma and hepatocarcinoma, are presented along with a brief discussion of the specificity of the cytologic diagnosis of hepatocarcinoma

A metastatic adrenal tumor from a hepatocellular carcinoma: combination therapy with transarterial chemoembolization and radiofrequency ablation

Energy Technology Data Exchange (ETDEWEB)

Lim, Hyun Jin; Cho, Yun Ku; Ahn, Yong Sik; Kim, Mi Young [Seoul Veterans Hospital, Seoul (Korea, Republic of)

2007-07-15

The adrenal gland is the second most common site of metastasis from a hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) for these tumors has been reported to be a potentially effective alternative to an adrenalectomy, especially for inoperable patients. However, for intermediate or large adrenal tumors, combination therapy of transarterial chemoembolization (TACE) and RFA can be attempted as it may reduce the heat sink effect. A 74-year-old patient presented with abdominal discomfort. Abdominal CT images revealed a 5.0 cm sized right adrenal mass. A percutaneous biopsy of the adrenal mass revealed a metastatic hepatocellular carcinoma. TACE was performed on the adrenal mass. However, a one-month follow-up CT image revealed a residual viable tumor. RFA was performed for the adrenal tumor six weeks after the TACE. No procedure-related major complications were noted. The serum alpha-fetoprotein level had also been normalized after the treatment, and 10-month follow-up CT images showed no definite evidence of viable adrenal tumor.

Exploring the role of CHI3L1 in pre-metastatic lungs of mammary tumor-bearing mice

Directory of Open Access Journals (Sweden)

Stephania eLibreros

2013-12-01

Full Text Available Elevated levels of chitinase-3-like-1 (CHI3L1 are associated with poor prognosis, shorter recurrence-free intervals and low survival in breast cancer patients. Breast cancer often metastasizes to the lung. We hypothesized that molecules expressed in the pre-metastatic lung microenvironment could support the newly immigrant tumor cells by providing growth and angiogenic factors. Macrophages are known to play an important role in tumor growth by releasing pro-angiogenic molecules. Using mouse mammary tumor models, we have previously shown that during neoplastic progression both the mammary tumor cells and splenic macrophages from tumor-bearing mice express higher levels of CHI3L1 compared to normal control mice. However, the role of CHI3L1 in inducing angiogenesis by macrophages at the pulmonary microenvironment to support newly arriving breast cancer cells is not yet known. In this study, we determined the expression of CHI3L1 in bronchoalveolar lavage macrophages and interstitial macrophages in regulating angiogenesis that could support the growth of newly immigrant mammary tumor cells into the lung. Here we show that in vitro treatment of pulmonary macrophages with recombinant murine CHI3L1 resulted in enhanced expression of pro-angiogenic molecules including CCL2, CXCL2 and MMP-9. We and others have previously shown that inhibition of CHI3L1 decreases the production of angiogenic molecules. In this study, we explored if in vivo administration of chitin microparticles has an effect on the expression of CHI3L1 and pro-angiogenic molecules in the lungs of mammary tumor-bearing mice. We show that treatment with chitin microparticles decreases the expression of CHI3L1 and pro-angiogenic molecules in the metastatic lung. These studies suggest that targeting CHI3L1 may serve as a potential therapeutic agent to inhibit angiogenesis and thus possibly tumor growth and metastasis.

Gastric injury from {sup 90}Y to left hepatic lobe tumors adjacent to the stomach: fact or fiction?

Energy Technology Data Exchange (ETDEWEB)

Gates, Vanessa L.; Hickey, Ryan; Marshall, Karen; Williams, Melissa; Salzig, Krystina; Lewandowski, Robert J. [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Salem, Riad [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States)

2015-12-15

Radioembolization with {sup 90}Y microspheres is a locoregional radiation therapy for unresectable hepatic neoplasm. Non-target delivery of {sup 90}Y microspheres resulting in gastrointestinal (GI) symptoms is a recognized complication; there is minimal knowledge regarding the radiation effect to the gastric wall from left hepatic lobe {sup 90}Y treatments. Our aim was to study the incidence of GI complications when the target tissue (hepatic parenchyma ± tumor) is in close proximity to the gastric wall. We hypothesized that liver (tumor) to stomach proximity does not correlate with increased toxicity. Between November 2011 and September 2013, we studied all patients who underwent left lobe radioembolization with {sup 90}Y glass microspheres. With Institutional Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these patients, identifying a subset of patients with the left hepatic lobe <1 cm from the gastric wall. Patients were seen in clinic 1 month posttreatment and subsequently at 3-month intervals. Short- and long-term gastric adverse events were tabulated. Ninety-seven patients successfully underwent left hepatic lobe {sup 90}Y microsphere radioembolization in which the average distance from the liver to the stomach wall was 1.0 ± 2.8 mm. The average dose for patients who received radioembolization to the left hepatic lobe was 109 ± 57 Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose for patients who received radioembolization to the left hepatic lobe with tumor within 1 cm of the gastric wall was 121 ± 41 Gy. There were no reportable or recordable medical events. Of the patients, 34 % reported abdominal pain that was grade 1-2; 65 % of the patients reported no abdominal pain. None of the 97 patients developed a clinically evident GI ulcer. Patients with left lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic radiation effects following radioembolization with glass

Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth.

Science.gov (United States)

Enderling, Heiko; Hlatky, Lynn; Hahnfeldt, Philip

2012-07-28

The role of the immune system in tumor progression has been a subject for discussion for many decades. Numerous studies suggest that a low immune response might be beneficial, if not necessary, for tumor growth, and only a strong immune response can counter tumor growth and thus inhibit progression. We implement a cellular automaton model previously described that captures the dynamical interactions between the cancer stem and non-stem cell populations of a tumor through a process of self-metastasis. By overlaying on this model the diffusion of immune reactants into the tumor from a peripheral source to target cells, we simulate the process of immune-system-induced cell kill on tumor progression. A low cytotoxic immune reaction continuously kills cancer cells and, although at a low rate, thereby causes the liberation of space-constrained cancer stem cells to drive self-metastatic progression and continued tumor growth. With increasing immune system strength, however, tumor growth peaks, and then eventually falls below the intrinsic tumor sizes observed without an immune response. With this increasing immune response the number and proportion of cancer stem cells monotonically increases, implicating an additional unexpected consequence, that of cancer stem cell selection, to the immune response. Cancer stem cells and immune cytotoxicity alone are sufficient to explain the three-step "immunoediting" concept - the modulation of tumor growth through inhibition, selection and promotion.

Benzimidazole as Novel Therapy for Hormone-Refractory Metastatic Prostate Cancer

Science.gov (United States)

2011-05-01

8 4 INTRODUCTION The focus of this project is to evaluate the anti-tumor effects of benzimidazoles as a...potential anti-metastatic prostate cancer therapy. We identified benzimidazoles , a class of anti-parasitic drug, in a drug screening process for...preferential anti-tumor activity on metastatic prostate cancer cells. We have data indicate that benzimidazoles have potent anti-tumor activities

Targeting Angiogenesis and Tumor Microenvironment in Metastatic Colorectal Cancer: Role of Aflibercept

Directory of Open Access Journals (Sweden)

Guido Giordano

2014-01-01

Full Text Available In the last decades, we have progressively observed an improvement in therapeutic options for metastatic colorectal cancer (mCRC treatment with a progressive prolongation of survival. mCRC prognosis still remains poor with low percentage of 5-year survival. Targeted agents have improved results obtained with standard chemotherapy. Angiogenesis plays a crucial role in colorectal cancer growth, proliferation, and metastasization and it has been investigated as a potential target for mCRC treatment. Accordingly, novel antiangiogenic targeted agents bevacizumab, regorafenib, and aflibercept have been approved for mCRC treatment as the result of several phase III randomized trials. The development of a tumor permissive microenvironment via the aberrant expression by tumor cells of paracrine factors alters the tumor-stroma interactions inducing an expansion of proangiogenic signals. Recently, the VELOUR study showed that addition of aflibercept to FOLFIRI regimen as a second-line therapy for mCRC improved significantly OS, PFS, and RR. This molecule represents a valid second-line therapeutic option and its peculiar ability to interfere with placental growth factor (PlGF/vascular endothelial growth factor receptor 1 (VEGFR1 axis makes it effective in targeting angiogenesis, inflammatory cells and in overcoming resistances to anti-angiogenic first-line treatment. Here, we discuss about Aflibercept peculiar ability to interfere with tumor microenvironment and angiogenic pathway.

Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study

International Nuclear Information System (INIS)

Chen, Kuo-Hsing; Shao, Yu-Yun; Chen, Ho-Min; Lin, Yu-Lin; Lin, Zhong-Zhe; Lai, Mei-Shu; Cheng, Ann-Lii; Yeh, Kun-Huei

2016-01-01

Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC). This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004–2010) and National Health Insurance (2004–2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure). A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08–1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18–1.78, P = .0003). Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC

Consistent expression of guanylyl cyclase-C in primary and metastatic gastrointestinal cancers.

Directory of Open Access Journals (Sweden)

Hadi Danaee

Full Text Available The transmembrane receptor guanylate cyclase-C (GCC has been found to be expressed in colorectal cancers. However, limited data are available on GCC protein expression in non-colorectal gastrointestinal tumors and few studies have reported whether GCC protein expression was consistently preserved in synchronous primary and metastatic cancer tissues.GCC protein status was assessed by immunohistochemistry in tumor specimens from individuals (n = 627 with gastrointestinal tumors, including esophageal (n = 130, gastric (n = 276, pancreatic (n = 136, and colorectal (n = 85 primary and metastatic tumors. Tissue specimens consisted of tissue microarrays containing esophageal, gastric, pancreatic tumors, and whole-slide tissue sections from colorectal cancer patients with matching primary and metastatic tumors.Among the evaluated esophageal, gastric, and pancreatic tumors, the frequency of GCC positivity at the protein level ranged from 59% to 68%. GCC was consistently expressed in primary and matched/synchronous metastatic lesions of colorectal cancer tissues derived from the same patients.This observational study demonstrated the protein expression of GCC across various gastrointestinal malignancies. In all cancer histotypes, GCC protein localization was observed predominantly in the cytoplasm compared to the membrane region of tumor cells. Consistent immunohistochemistry detection of GCC protein expression in primary colorectal cancers and in their matched liver metastases suggests that the expression of GCC is maintained throughout the process of tumor progression and formation of metastatic disease.

Metastatic Breast Cancer With ESR1 Mutation: Clinical Management Considerations From the Molecular and Precision Medicine (MAP) Tumor Board at Massachusetts General Hospital.

Science.gov (United States)

Bardia, Aditya; Iafrate, John A; Sundaresan, Tilak; Younger, Jerry; Nardi, Valentina

2016-09-01

: The last decade in oncology has witnessed impressive response rates with targeted therapies, largely because of collaborative efforts at understanding tumor biology and careful patient selection based on molecular fingerprinting of the tumor. Consequently, there has been a push toward routine molecular genotyping of tumors, and large precision medicine-based clinical trials have been launched to match therapy to the molecular alteration seen in a tumor. However, selecting the "right drug" for an individual patient in clinic is a complex decision-making process, including analytical interpretation of the report, consideration of the importance of the molecular alteration in driving growth of the tumor, tumor heterogeneity, the availability of a matched targeted therapy, efficacy and toxicity considerations of the targeted therapy (compared with standard therapy), and reimbursement issues. In this article, we review the key considerations involved in clinical decision making while reviewing a molecular genotyping report. We present the case of a 67-year-old postmenopausal female with metastatic estrogen receptor-positive (ER+) breast cancer, whose tumor progressed on multiple endocrine therapies. Molecular genotyping of the metastatic lesion revealed the presence of an ESR1 mutation (encoding p.Tyr537Asn), which was absent in the primary tumor. The same ESR1 mutation was also detected in circulating tumor DNA (ctDNA) extracted from her blood. The general approach for interpretation of genotyping results, the clinical significance of the specific mutation in the particular cancer, potential strategies to target the pathway, and implications for clinical practice are reviewed in this article. ER+ breast tumors are known to undergo genomic evolution during treatment with the acquisition of new mutations that confer resistance to treatment.ESR1 mutations in the ligand-binding domain of ER can lead to a ligand-independent, constitutively active form of ER and mediate

A meta-analysis of 18F-Fluoride positron emission tomography for assessment of metastatic bone tumor

International Nuclear Information System (INIS)

Tateishi, Ukihide; Morita, Satoshi; Taguri, Masataka

2010-01-01

The aim of this study was to assess the diagnostic performance of 18 F-Fluoride positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) compared with bone scintigraphy (BS) planar or BS planar and single photon emission computed tomography (SPECT) in evaluating patients with metastatic bone tumor. We performed a meta-analysis of all available studies addressing the diagnostic accuracy of 18 F-Fluoride PET, 18 F-Fluoride PET/CT, BS planar, and BS planar and SPECT for detecting the metastatic bone tumor. We determined sensitivities and specificities across studies, calculated positive and negative likelihood ratios, and drew summary receiver operating characteristic curves using hierarchical regression models. We also compared the effective dose and cost-effectiveness estimated by data from the enrolled studies between 18 F-Fluoride PET or PET/CT and BS planar or BS planar and SPECT. When comparing all studies with data on 18 F-Fluoride PET or PET/CT, sensitivity and specificity were 96.2% [95% confidence interval (CI) 93.5-98.9%] and 98.5% (95% CI 97.0-100%), respectively, on a patient basis and 96.9% (95% CI 95.9-98.0%) and 98.0% (95% CI 97.1-98.9%), respectively, on a lesion basis. The Az values of 18 F-Fluoride PET or PET/CT were 0.986 for the patient basis and 0.905 for the lesion basis, whereas those of BS or BS and SPECT were 0.866 for the patient basis and 0.854 for the lesion basis. However, the estimated effective dose and average cost-effective ratio were poorer for 18 F-Fluoride PET or PET/CT than those of BS planar or BS planar and SPECT. 18 F-Fluoride PET or PET/CT has excellent diagnostic performance for the detection of metastatic bone tumor, but the estimated effective dose and average cost-effective ratio are at a disadvantage compared with BS planar or BS planar and SPECT. (author)

Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

International Nuclear Information System (INIS)

Nguyen, Xuan Canh; Nguyen, Van Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

2014-01-01

To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUV pt ), maxSUV of whole-body tumors (maxSUV wb ) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSCLC were enrolled. Seventeen patients had Stage IIIA, 21 Stage IIIB, and 45 Stage IV. maxSUV pt , maxSUV wb , sumaxSUV, age, gender, tumor-cell type, T stage, N stage, overall stage, primary tumor size, and specific treatment were analyzed for correlation with overall survival. Median follow-up duration was 13 months. Fifty patients were dead during a median follow-up time of 11 months and 33 patients were alive with a median time of 15 months. Univariate analysis revealed that overall survival was significantly correlated with sumaxSUV (≥35 vs. <35, P = 0.004), T stage (T4 vs. T1-T3, P = 0.025), overall stage (IV vs. III, P = 0.002), gender (male vs. female, P = 0.029) and specific treatment (no vs. yes, P = 0.011). maxSUV pt and maxSUV wb were not correlated with overall survival with P value of 0.139 and 0.168, respectively. Multivariate analysis identified sumaxSUV, T stage, gender, and specific treatment as independent prognostic indicators. Patients with a sumaxSUV of ≥35 were 1.921 times more likely to die than those with a sumaxSUV of < 35 (P = 0.047). Median survival time was 14 months for patients with sumaxSUV ≥ 35 compared with 20 months for those with sumaxSUV < 35. In patients with metastatic NSCLC, sumaxSUV with cut-off of 35 was much more significant for survival prognosis (P = 0.021). sumaxSUV is a new prognostic measure, independent of tumor stage, gender, and specific treatment in advanced NSCLC. sumaxSUV may be better than maxSUV pt and maxSUV wb in

The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts.

Science.gov (United States)

Peinado, Héctor; Lavotshkin, Simon; Lyden, David

2011-04-01

Metastasis is a multistep process that requires acquisition of malignant cell phenotypes which allow tumor cells to escape from the primary tumor site. Each of the steps during metastatic progression involves co-evolution of the tumor and its microenvironment. Although tumor cells are the driving force of metastasis, new findings suggest that the host cells within the tumor microenvironment play a key role in influencing metastatic behavior. Many of these contributing cells are derived from the bone marrow; in particular, recruited bone marrow progenitor cells generate the "pre-metastatic niche" to which the tumor cells metastasize. Analysis of the molecular mechanisms involved in pre-metastatic niche formation has revealed that secreted soluble factors are key players in bone marrow cell mobilization during metastasis. In addition, membrane vesicles derived from both tumor and host cells have recently been recognized as new candidates with important roles in the promotion of tumor growth and metastasis. This review describes old ideas and presents new insights into the role of tumor and bone marrow-derived microvesicles and exosomes in pre-metastatic niche formation and metastasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Non-metastatic Ewing's sarcoma family of tumors of bone in adolescents and adults: prognostic factors and clinical outcome-single institution results.

Science.gov (United States)

Oksüz, Didem Colpan; Tural, Deniz; Dincbas, Fazilet Öner; Dervisoglu, Sergülen; Turna, Hande; Hiz, Murat; Kantarci, Fatih; Ceylaner, Beyhan; Koca, Sedat; Mandel, Nil Molinas

2014-01-01

There is limited data regarding outcomes of Ewing's sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewing's sarcoma family of tumors. From 1992-2008, 90 adolescents and adults with Ewing's sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics. The median age was 21 years (range, 13-50). Most patients (74%) were >17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 patients. Twenty-one patients received preoperative and 13 patients postoperative radiotherapy. Median follow-up was 43 months (range, 7-167). The 5-year event-free and overall survival rates for all patients were 44% and 49%, respectively. On univariate survival analysis, event-free and overall survival were worse for patients >17 years of age, tumor size >8 cm in diameter, an axial location, positive surgical margins, and poor histopathological response (<90% necrosis). Age, tumor site and tumor size on event-free and overall survival remained significant on multivariate analysis. We identified age, tumor size, and tumor site as independent prognostic factors, in accord with the Western literature. These patients require novel treatment modalities.

Metastatic spreading and growth of rhabdomyosarcoma in exposure to hyperglycemia, hyperthermia and ionizing radiation

International Nuclear Information System (INIS)

Ul'yanenko, S.E.; Salamatina, N.A.; Dedenkov, A.N.

1985-01-01

Under the effect of local UHF-hyperthermia, short-term hyperglycemia and ionizing radiation on metastasing strain of rhabdomysarcoma an increase in metastatic spreading or stimulated growth of primary tumor are not noticed. Otherwise, it is stated that hyperglycemia and hyperthermia thrice-used prevent from metastatic spreading of the tumor. Ionizing radiation decelerates both tumor growth and to a least extent its metastatic spreading

A preoperative mathematic model for computed tomographic guided microwave ablation treatment of hepatic dome tumors.

Science.gov (United States)

Gao, Fei; Wang, Guo-Bao; Xiang, Zhan-Wang; Yang, Bin; Xue, Jing-Bing; Mo, Zhi-Qiang; Zhong, Zhi-Hui; Zhang, Tao; Zhang, Fu-Jun; Fan, Wei-Jun

2016-05-03

This study sought to prospectively evaluate the feasibility and safety of a preoperative mathematic model for computed tomographic(CT) guided microwave(MW) ablation treatment of hepatic dome tumors. This mathematic model was a regular cylinder quantifying appropriate puncture routes from the bottom up. A total of 103 patients with hepatic dome tumors were enrolled and randomly divided into 2 groups based on whether this model was used or not: Group A (using the model; n = 43) versus Group B (not using the model; n = 60). All tumors were treated by CT-guided MW ablation and follow-up contrast CT were reviewed. The average number of times for successful puncture, average ablation time, and incidence of right shoulder pain were less in Group A than Group B (1.4 vs. 2.5, P = 0.001; 8.8 vs. 11.1 minutes, P = 0.003; and 4.7% vs. 20%, P = 0.039). The technical success rate was higher in Group A than Group B (97.7% vs. 85.0%, P = 0.032). There were no significant differences between the two groups in primary and secondary technique efficacy rates (97.7% vs. 88.3%, P = 0.081; 90.0% vs. 72.7%, P = 0.314). No major complications occurred in both groups. The mathematic model of regular cylinder is feasible and safe for CT-guided MW ablation in treating hepatic dome tumors.

Primary hepatic actinomycosis mimicking a tumor (inflammatory pseudotumor: Case report and literature review

Directory of Open Access Journals (Sweden)

Ayşe Batirel

2015-06-01

Full Text Available Actinomycosis often manifests with abscesses in the cervicofacial region. Hepatic involvement occurs usually secondary to an intraabdominal infection. “Isolated or primary hepatic actinomycosis (PHA defines actinomycosis in which the source of infection cannot be demonstrated elsewhere. Herein, we aimed to highlight hepatic actinomycosis in the differential diagnosis of hepatic mass lesions, and also its occurrence even in patients without underlying risk factors. A 24-year-old man, who presented with epigastric and right-upper-quadrant abdominal pain, fever, weight loss, and had a tumor-like mass in the liver was admitted to our hospital. He had no predisposing risk factors or comorbidities. We reviewed all the cases with PHA, who had no predisposing risk factors, in English medical literature from 1993 to 2014. Actinomycotic hepatic pseudotumors should be considered in the differential diagnosis of solitary liver lesions even in patients without any predisposing factors. Multi-disciplinary approach is important in the diagnosis and management. J Microbiol Infect Dis 2015;5(2: 79-84

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of ...

CT perfusion of the liver during selective hepatic arteriography. Pure arterial blood perfusion of liver tumor and parenchyma

International Nuclear Information System (INIS)

Komemushi, Atsushi; Tanigawa, Noboru; Kojima, Hiroyuki; Kariya, Shuji; Sawada, Satoshi

2003-01-01

The purpose of this study was to quantify pure arterial blood perfusion of liver tumor and parenchyma by using CT perfusion during selective hepatic arteriography. A total of 44 patients underwent liver CT perfusion study by injection of contrast medium via the hepatic artery. CT-perfusion parameters including arterial blood flow, arterial blood volume, and arterial mean transit time in the liver parenchyma and liver tumor were calculated using the deconvolution method. The CT-perfusion parameters and vascularity of the tumor were compared. A complete analysis could be performed in 36 of the 44 patients. For liver tumor and liver parenchyma, respectively, arterial blood flow was 184.6±132.7 and 41.0±27.0 ml/min/100 g, arterial blood volume was 19.4±14.6 and 4.8±4.2 ml/100 g, and arterial mean transit time was 8.9±4.2 and 10.2±5.3 sec. Arterial blood flow and arterial blood volume correlated significantly with the vascularity of the tumor; however no correlation was detected between arterial mean transit time and the vascularity of the tumor. This technique could be used to quantify pure hepatic arterial blood perfusion. (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.

Dynamic computed tomography in various hepatic diseases. Particular reference to detection and differential diagnosis of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Takemoto, Kazumasa

1985-03-01

Studied were 140 cases of hepatoma, 40 of metastatic liver tumor, 18 of hemangioma, 9 of liver cirrhosis, 10 of chronic hepatitis and 10 patients with no liver disease. The dynamic CT was obtained before, 10, 30 and 50 seconds after an intravenous bolus injection of 50 ml of 65 % meglumine diatrizoate. Normal liver parenchyma and portal vein were slightly enhanced on the arterial phase and moderately enhanced on the portal phase of the dynamic CT. There was no significant change in case of chronic hepatitis, but in case of liver cirrhosis, the liver parenchyma was less enhanced than the normal liver on the portal phase. Tumor enhancement on the arterial phase was classified into 6 patterns, namely, A : homogeneous, B : inhomogeneous, C : patchy, D : ring, E : peripheral and F : no enhancement, while time-density-change was classified into 4 types, namely, type I : the tumor was most enhanced on the arterial phase, type II : the tumor was most enhanced on the portal phase, type III : tumor enhancement increased with time, type IV : there were no significant changes with time. Hepatoma was characterized by patterns A, B and C tumor enhancement and type I time-density-change, while metastatic liver tumor featured patterns D and F tumor enhancement and hemangioma was characteristic in indicating pattern E tumor enhancement and type III time-density-change. The rate of accurate diagnosis was 92 %. Small hepatoma (less than 5 cm in diameter) could be detected by conventional CT only in 38 out of 50 cases (76 %), while dynamic CT revealed an additional 8 cases. Out of 21 cases of portal vein thrombosis, 14 cases (66.7 %) were detected by the conventional CT but dynamic CT improved the rate of detection to 92.0 %. Dynamic CT also revealed 6 cases of arterioportal shunt which could not be detected at all by conventional CT. Thus dynamic CT provides useful information and should be considered as one of the routine tests in CT examination of the liver. (J.P.N.).

Doege-Potter syndrome presenting with hypoinsulinemic hypoglycemia in a patient with a malignant extrapleural solitary fibrous tumor: a case report

Directory of Open Access Journals (Sweden)

Schutt Robert C

2013-01-01

Full Text Available Abstract Introduction Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. This tumor causes hypoglycemia by the secretion of a prohormone form of insulin-like growth factor II. We describe the diagnosis and management of Doege-Potter syndrome and the use of transarterial chemoembolization in a patient with a malignant extrapleural solitary fibrous tumor. Case presentation Our patient was a 64-year-old Caucasian woman who initially presented with urinary incontinence and was found to have a 14.5×9.0×9.0cm retroperitoneal solitary fibrous tumor compressing her bladder. Her tumor was surgically resected but recurred with multiple hepatic metastatic lesions. The hepatic metastases progressed despite systemic chemotherapy and treatment with doxorubicin transarterial chemoembolization. Her course was complicated by the development of recurrent fasting hypoglycemia, most likely secondary to Doege-Potter syndrome. Her hypoglycemia was managed with corticosteroid therapy and frequent scheduled nutrient intake overnight. Conclusions The rarity of hepatic solitary fibrous tumors and consequent lack of controlled trials make this report significant in that it describes the diagnostic approach to Doege-Potter syndrome, describes our experience with the use of doxorubicin transarterial chemoembolization, and presents management options for tumor-associated hypoglycemia in the case of extensive disease not amenable to surgical resection.

Differentiation of Glioblastomas from Metastatic Brain Tumors by Tryptophan Uptake and Kinetic Analysis: A Positron Emission Tomographic Study with Magnetic Resonance Imaging Comparison

Directory of Open Access Journals (Sweden)

David O. Kamson

2013-07-01

Full Text Available Differentiating high-grade gliomas from solitary brain metastases is often difficult by conventional magnetic resonance imaging (MRI; molecular imaging may facilitate such discrimination. We tested the accuracy of α[11C]methyl-L-tryptophan (AMT–positron emission tomography (PET to differentiate newly diagnosed glioblastomas from brain metastases. AMT-PET was performed in 36 adults with suspected brain malignancy. Tumoral AMT accumulation was measured by standardized uptake values (SUVs. Tracer kinetic analysis was also performed to separate tumoral net tryptophan transport (by AMT volume of distribution [VD] from unidirectional uptake rates using dynamic PET and blood input function. Differentiating the accuracy of these PET variables was evaluated and compared to conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV showed the highest accuracy (74% and the tumor/cortex VD ratio had the highest positive predictive value (82%. The combined accuracy of MRI (size of contrast-enhancing lesion and AMT-PET reached up to 93%. For ring-enhancing lesions, tumor/cortex SUV ratios were higher in glioblastomas than in metastatic tumors and could differentiate these two tumor types with > 90% accuracy. These results demonstrate that evaluation of tryptophan accumulation by PET can enhance pretreatment differentiation of glioblastomas and metastatic brain tumors. This approach may be particularly useful in patients with a newly diagnosed solitary ring-enhancing mass.

Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer.

Science.gov (United States)

Zhao, Shanshan; Geybels, Milan S; Leonardson, Amy; Rubicz, Rohina; Kolb, Suzanne; Yan, Qingxiang; Klotzle, Brandy; Bibikova, Marina; Hurtado-Coll, Antonio; Troyer, Dean; Lance, Raymond; Lin, Daniel W; Wright, Jonathan L; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

2017-01-01

Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential. Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum. Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Study on the possible usefulness of the serum markers ICTP, IGF-1 and BGP for diagnosis of hepatic carcinoma

International Nuclear Information System (INIS)

Zhong Ying; Du Minghua; Zhang Jiao; Wu Wei

2006-01-01

Objective: To study the relationship between the changes of serum levels of the hepatic fibrosis markers ICTP, IGF-I, BGP and the conventional hepatic carcinoma markers as well as hepatic function indicators in patients with primary and metastatic hepatic cancers. Methods: Serum ICTP, IGF-I, BGP (with RIA), AFP, CEA, CA-199 (with CLIA) contents were determined and conventional liver function tests (ALT, AST, γ-GT) were examined in 51 patients with liver carcinoma (primary 28, metastatic 23) and 30 controls. Results: The serum levels of ICTP, IGF-I and BGP in all the patients were significantly higher than those in controls (P 0.05). The levels of CEA and CA-199 were significantly higher in patients with metastatic hepatic carcinoma than those in patients with primary hepatic carcinoma (P 0.05). Levels of BGP were positively correlated with the AST and γ-GT levels (P<0.05). Conclusion: Serum levels of ICTP, IGF-I, BGP were increased in both primary and metastatic hepatic carcinoma. (authors)

Bone tumors

International Nuclear Information System (INIS)

Unni, K.K.

1988-01-01

This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

Imaging Mitochondrial Redox Potential and Its Possible Link to Tumor Metastatic Potential

Science.gov (United States)

Li, Lin Z.

2012-01-01

Cellular redox states can regulate cell metabolism, growth, differentiation, motility, apoptosis, signaling pathways, and gene expressions etc. Growing body of literature suggest importance of redox status for cancer progression. While most studies on redox state were done on cells and tissue lysates, it is important to understand the role of redox state in tissue in vivo/ex vivo and image its heterogeneity. Redox scanning is a clinically-translatable method for imaging tissue mitochondrial redox potential with a submillimeter resolution. Redox scanning data in mouse models of human cancers demonstrate a correlation between mitochondrial redox state and tumor metastatic potential. I will discuss the significance of this correlation and possible directions for future research. PMID:22895837

Laser-induced thermo ablation of hepatic tumors: an update review

International Nuclear Information System (INIS)

D'Ippolito, Giuseppe; Ribeiro, Marcelo

2004-01-01

Laser-induced thermo ablation has been used as a reliable method for producing coagulation necrosis in hepatic tumors in patients who are not suitable for surgical treatment. The procedure can be performed percutaneously, using image-guiding methods, by open laparotomy or laparoscopy. We review the current literature and discuss the principles, indications, complications and clinical results as well as the potential limitations and contraindications of this novel technique. (author)

Characterization of hepatic tumors using [11C]metomidate through positron emission tomography

DEFF Research Database (Denmark)

Roivainen, Anne; Naum, Alexandru; Nuutinen, Heikki

2013-01-01

ABSTRACT: BACKGROUND: Using positron emission tomography (PET), we compared two tracers, [11C]metomidate ([11C]MTO) and [11C]acetate ([11C]ACE), for the characterization of hepatic tumors. METHODS: Thirty-three patients underwent PET with [11C]MTO and [11C]ACE and magnetic resonance imaging (MRI...

A massive hepatic tumor demonstrating hepatocellular, cholangiocarcinoma and neuroendocrine lineages: A case report and review of the literature

Directory of Open Access Journals (Sweden)

Rachel E. Beard

2017-01-01

Conclusion: This is one of the only reports of a hepatic tumor arising from hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine lineages. Increased awareness of this tumor type may optimize improve future management.

Viable tumor volume: Volume of interest within segmented metastatic lesions, a pilot study of proposed computed tomography response criteria for urothelial cancer

International Nuclear Information System (INIS)

Folio, Les Roger; Turkbey, Evrim B.; Steinberg, Seth M.; Apolo, Andrea B.

2015-01-01

Highlights: • It is clear that 2D axial measurements are incomplete assessments in metastatic disease; especially in light of evolving antiangiogenic therapies that can result in tumor necrosis. • Our pilot study demonstrates that taking volumetric density into account can better predict overall survival when compared to RECIST, volumetric size, MASS and Choi. • Although volumetric segmentation and further density analysis may not yet be feasible within routine workflows, the authors believe that technology advances may soon make this possible. - Abstract: Objectives: To evaluate the ability of new computed tomography (CT) response criteria for solid tumors such as urothelial cancer (VTV; viable tumor volume) to predict overall survival (OS) in patients with metastatic bladder cancer treated with cabozantinib. Materials and methods: We compared the relative capabilities of VTV, RECIST, MASS (morphology, attenuation, size, and structure), and Choi criteria, as well as volume measurements, to predict OS using serial follow-up contrast-enhanced CT exams in patients with metastatic urothelial carcinoma. Kaplan–Meier curves and 2-tailed log-rank tests compared OS based on early RECIST 1.1 response against each of the other criteria. A Cox proportional hazards model assessed response at follow-up exams as a time-varying covariate for OS. Results: We assessed 141 lesions in 55CT scans from 17 patients with urothelial metastasis, comparing VTV, RECIST, MASS, and Choi criteria, and volumetric measurements, for response assessment. Median follow-up was 4.5 months, range was 2–14 months. Only the VTV criteria demonstrated a statistical association with OS (p = 0.019; median OS 9.7 vs. 3.5 months). Conclusion: This pilot study suggests that VTV is a promising tool for assessing tumor response and predicting OS, using criteria that incorporate tumor volume and density in patients receiving antiangiogenic therapy for urothelial cancer. Larger studies are warranted to

Local and systemic tumor immune dynamics

Science.gov (United States)

Enderling, Heiko

Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

Targeted Therapy of Hepatitis B Virus-Related Hepatocellular Carcinoma: Present and Future

Directory of Open Access Journals (Sweden)

Sarene Koh

2016-02-01

Full Text Available Cancer immunotherapy using a patient’s own T cells redirected to recognize and kill tumor cells has achieved promising results in metastatic melanoma and leukemia. This technique involves harnessing a patient’s T cells and then delivering a gene that encodes a new T cell receptor (TCR or a chimeric antigen receptor (CAR that allow the cells to recognize specific cancer antigens. The prospect of using engineered T cell therapy for persistent viral infections like hepatitis B virus (HBV and their associated malignancies is promising. We recently tested in a first-in-man clinical trial, the ability of HBV-specific TCR-redirected T cells to target HBsAg-productive hepatocellular carcinoma (HCC and demonstrated that these redirected T cells recognized HCC cells with HBV–DNA integration [1] We discuss here the possibility to use HBV-specific TCR-redirected T cells targeting hepatitis B viral antigens as a tumor specific antigen in patients with HBV-related HCC, and the potential challenges facing the development of this new immunotherapeutic strategy.

Combined Evaluation of AFP, CA15-3, CA125, CA19-9, and CEA Tumor Markers in Patients with Hepatitis B and C.

Science.gov (United States)

Assmar, Mehdi; Yeganeh, Sara; Mansourghanaei, Fariborz; Amirmozafari, Nour

2016-12-01

This study aimed to determine the role of tumor markers AFP, CA15-3, CA125, CA19-9 and CEA in patients with hepatitis B and C. This descriptive cross-sectional study was performed from Oct 2012 to Oct 2014. Serum samples of 129 patients with hepatitis B and C referred to Guilan Liver and Digestive Disease Research Center in Rasht, Iran were collected and checked for the existence of the listed tumor markers by ELISA. No increase in serum levels of tumor marker CA19-9, CEA and CA15-3 were seen in patients with hepatitis ( P >0.05). In patients with hepatitis B, increase in CA125 were observed ( P =0.03). In hepatitis C patients, there was an increase in AFP levels ( P =0.03). The levels of AFP and CA125 markers were high in hepatitis C and hepatitis B, respectively. However, the increased levels were not seen is malignancy. Due to the small sample size, further study is necessary to find the reasons of the increase.

MRI findings of hepatic hemangioma with a special reference to tumor size

Energy Technology Data Exchange (ETDEWEB)

Ogata, Ichiro; Yamashita, Yasuyuki; Hatanaka, Yoshimi; Nishiharu, Taizi; Urata, Zyouzi; Matsukawa, Tetsuya; Yamamoto, Hiroaki; Takahashi, Mutsumasa [Kumamoto Univ. (Japan). School of Medicine

1997-01-01

The purpose of this research is to define the appearance of hepatic hemangiomas on T{sub 2}-weighted and dynamic gadolinium-enhanced FLASH magnetic resonance (MR) images. With 1.5-T MR imaging, T{sub 1} and T{sub 2}-weighted spin echo and dynamic gadolinium-enhanced FLASH, and postcontrast, T{sub 1}-weighted spin echo images were obtained in 74 patients. Signal intensity, internal architecture, margin on T{sub 2}-weighted images and pattern of enhancement on dynamic images were correlated with tumor size. As a result, in all, 96 hemangiomas were depicted. On T{sub 2}-weighted images, 90 tumors were very hyperintense and 6 tumors were slightly hyperintense relative to the surrounding liver. Tumors of very hyperintensity, homogenous architecture or with septation tended to be larger than those without these findings (p<0.0001). 53 tumors showed peripheral enhancement, while 17 tumors showed total enhancement. Tumor size of former enhancement pattern was significantly larger than that of later enhancement pattern. So we concluded that MR appearance of hemangioma has close relationship with tumor size. (author)

MRI findings of hepatic hemangioma with a special reference to tumor size

International Nuclear Information System (INIS)

Ogata, Ichiro; Yamashita, Yasuyuki; Hatanaka, Yoshimi; Nishiharu, Taizi; Urata, Zyouzi; Matsukawa, Tetsuya; Yamamoto, Hiroaki; Takahashi, Mutsumasa

1997-01-01

The purpose of this research is to define the appearance of hepatic hemangiomas on T 2 -weighted and dynamic gadolinium-enhanced FLASH magnetic resonance (MR) images. With 1.5-T MR imaging, T 1 and T 2 -weighted spin echo and dynamic gadolinium-enhanced FLASH, and postcontrast, T 1 -weighted spin echo images were obtained in 74 patients. Signal intensity, internal architecture, margin on T 2 -weighted images and pattern of enhancement on dynamic images were correlated with tumor size. As a result, in all, 96 hemangiomas were depicted. On T 2 -weighted images, 90 tumors were very hyperintense and 6 tumors were slightly hyperintense relative to the surrounding liver. Tumors of very hyperintensity, homogenous architecture or with septation tended to be larger than those without these findings (p<0.0001). 53 tumors showed peripheral enhancement, while 17 tumors showed total enhancement. Tumor size of former enhancement pattern was significantly larger than that of later enhancement pattern. So we concluded that MR appearance of hemangioma has close relationship with tumor size. (author)

CT hepatic perfusion measurement: Comparison of three analytic methods

International Nuclear Information System (INIS)

Kanda, Tomonori; Yoshikawa, Takeshi; Ohno, Yoshiharu; Kanata, Naoki; Koyama, Hisanobu; Takenaka, Daisuke; Sugimura, Kazuro

2012-01-01

Objectives: To compare the efficacy of three analytic methods, maximum slope (MS), dual-input single-compartment model (CM) and deconvolution (DC), for CT measurements of hepatic perfusion and assess the effects of extra-hepatic systemic factors. Materials and methods: Eighty-eight patients who were suspected of having metastatic liver tumors underwent hepatic CT perfusion. The scans were performed at the hepatic hilum 7–77 s after administration of contrast material. Hepatic arterial and portal perfusions (HAP and HPP, ml/min/100 ml) and arterial perfusion fraction (APF, %) were calculated with the three methods, followed by correlation assessment. Partial correlation analysis was used to assess the effects on hepatic perfusion values by various factors such as age, sex, risk of cardiovascular diseases, arrival time of contrast material at abdominal aorta, transit time from abdominal aorta to hepatic parenchyma, and liver dysfunction. Results: Mean HAP of MS was significantly higher than DC. HPP of CM was significantly higher than MS and CM, and HPP of MS was significantly higher than DC. There was no significant difference in APF. HAP and APF showed significant and moderate correlations among the methods. HPP showed significant and moderate correlations between CM and DC, and poor correlation between MS and CM or DC. All methods showed weak correlations between HAP or APF and age or sex. Finally, MS showed weak correlations between HAP or HPP and arrival time or cardiovascular risks. Conclusions: Hepatic perfusion values arrived at with the three methods are not interchangeable. CM and DC are less susceptible to extra-hepatic systemic factors

Primary isolated hepatic tuberculosis

International Nuclear Information System (INIS)

Sheikh, A.S.F.; Qureshi, I.H.; Saba, K.; Bukhari, M.H.

2013-01-01

Isolated hepatic tuberculosis without pulmonary or bowel involvement is a diagnostic challenge and can cause considerable morbidity. A young lady from Lahore presented with fever, pain in right hypochondria, nausea and weight loss. CT scan of abdomen showed multiple small hypodense non-enhancing lesions and a heterogeneous texture of liver. Biopsy confirmed the diagnosis of hepatic tuberculosis. It was concluded a case of isolated hepatic tuberculosis without evidence of other primary sites involvement. It is important to consider tuberculosis in the differential diagnosis when suspecting lymphoproliferative or metastatic diseases in a patient with vague symptoms and abnormal hepatic texture on CT. (author)

Impact of third-line treatment with irinotecan plus cetuximab on non-tumor standardized uptake values in patients with metastatic colorectal cancer

DEFF Research Database (Denmark)

Andersen, Kim Francis; Skougaard, Kristin; Nielsen, Anne Lerberg

2012-01-01

The correct interpretation of metabolic response in cancer cells to therapy requires knowledge of how tumor-free tissue responds to the same treatment. The aim of this study was to evaluate standardized uptake values (SUVs) in tumor-free regions of patients with metastatic colorectal cancer prior...... body mass were registered. The procedure was repeated for a follow-up scan two weeks following a single administration of the third-line treatment with irinotecan plus cetuximab. The mean differences in SUV prior to and following therapy were non-significant (P>0.05) in all the registered tumor...

Flexible applicator systems for radiofrequency ablation (RFA) of hepatic tumors

International Nuclear Information System (INIS)

Gebauer, B.; Gaffke, G.; Felix, R.; Stroszczynski, C.; Huenerbein, M.

2003-01-01

Purpose: To report our experience with flexible applicators in radiofrequency ablation (RFA) of hepatic tumors. Materials and Methods: In 6 liver tumors in 6 patients, a flexible RFA-applicator system (RITA StarBurst FLEX, RITA Medical Systems, Mountain View, CA, USA) was placed under CT guidance. The Seldinger technique with an 11G access system (RITA StarBurst Access) was used to place the application system into the liver. Before and within a week after the ablation, all tumors were investigated with contrast-enhanced MRI. Results: The Seldinger technique accommodated the placement of a thin 17.5-gauge needle for the initial puncture, enabling easy adjustment of the position of the needle. The flexible applicator of the RFA system could be placed in 4.5 (±1.8) minutes on average. Conclusion: Flexible applicators facilitate CT-guided RFA and can be placed using the Seldinger technique. (orig.) [de

Assessment of diagnosing metastatic bone tumor on T2*-weighted images. Comparison between turbo spin echo (TSE) method and gradient echo (GE) method

International Nuclear Information System (INIS)

Hayashi, Takahiko; Sugiyama, Akira; Katayama, Motoyuki

1996-01-01

We examined the usefulness of T2 * weighted gradient field echo images for diagnosis for metastatic bone tumors in comparison with T2 weighted turbo spin echo (fast spin echo) images. In T2 * weighted gradient field echo sequence to obtain maximum contrast-to-noise ratio (CNR), we experimentally manipulated flip angle (FA) (5deg-90deg), repetition time (TR) (400, 700 msec), and echo time (TE) (10-50 msec). The best CNR was 16.4 in fast low angle shot (FLASH) (TE: 24 msec, TR: 700 msec, FA: 40deg). Magnetic resonance imaging was carried out in 28 patients with metastatic bone tumors. In addition to conventional T1 weighted spin echo images, T2 weighted turbo spin echo (fast spin echo images) and T2 * weighted gradient field echo images were obtained. T2 * weighted gradient field echo images were superior to T2 weighted turbo spin echo (fast spin echo) images in delineating the tumors, adjacent fat tissues, and bone marrow. (author)

Activated Hepatic Stellate Cells Induce Tumor Progression of Neoplastic Hepatocytes in a TGF-β Dependent Fashion

Science.gov (United States)

MIKULA, M.; PROELL, V.; FISCHER, A.N.M.; MIKULITS, W.

2010-01-01

The development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells. For both tumorigenesis and hepatic fibrogenesis, transforming growth factor (TGF)-β signaling executes key roles and therefore is considered as a hallmark of these pathological events. By employing cellular transplantation we show that the interaction of neoplastic MIM-R hepatocytes with the tumor microenvironment, containing either activated hepatic stellate cells (M1-4HSCs) or myofibroblasts derived thereof (M-HTs), induces progression in malignancy. Cotransplantation of MIM-R hepatocytes with M-HTs yielded strongest MIM-R generated tumor formation accompanied by nuclear localization of Smad2/3 as well as of β-catenin. Genetic interference with TGF-β signaling by gain of antagonistic Smad7 in MIM-R hepatocytes diminished epithelial dedifferentiation and tumor progression upon interaction with M1-4HSCs or M-HTs. Further analysis showed that tumors harboring disrupted Smad signaling are devoid of nuclear β-catenin accumulation, indicating a crosstalk between TGF-β and β-catenin signaling. Together, these data demonstrate that activated HSCs and myofibroblasts directly govern hepatocarcinogenesis in a TGF-β dependent fashion by inducing autocrine TGF-β signaling and nuclear β-catenin accumulation in neoplastic hepatocytes. These results indicate that intervention with TGF-β signaling is highly promising in liver cancer therapy. PMID:16883581

An in vitro correlation of mechanical forces and metastatic capacity

International Nuclear Information System (INIS)

Indra, Indrajyoti; Undyala, Vishnu; Kandow, Casey; Thirumurthi, Umadevi; Beningo, Karen A; Dembo, Micah

2011-01-01

Mechanical forces have a major influence on cell migration and are predicted to significantly impact cancer metastasis, yet this idea is currently poorly defined. In this study we have asked if changes in traction stress and migratory properties correlate with the metastatic progression of tumor cells. For this purpose, four murine breast cancer cell lines derived from the same primary tumor, but possessing increasing metastatic capacity, were tested for adhesion strength, traction stress, focal adhesion organization and for differential migration rates in two-dimensional and three-dimensional environments. Using traction force microscopy (TFM), we were surprised to find an inverse relationship between traction stress and metastatic capacity, such that force production decreased as the metastatic capacity increased. Consistent with this observation, adhesion strength exhibited an identical profile to the traction data. A count of adhesions indicated a general reduction in the number as metastatic capacity increased but no difference in the maturation as determined by the ratio of nascent to mature adhesions. These changes correlated well with a reduction in active beta-1 integrin with increasing metastatic ability. Finally, in two dimensions, wound healing, migration and persistence were relatively low in the entire panel, maintaining a downward trend with increasing metastatic capacity. Why metastatic cells would migrate so poorly prompted us to ask if the loss of adhesive parameters in the most metastatic cells indicated a switch to a less adhesive mode of migration that would only be detected in a three-dimensional environment. Indeed, in three-dimensional migration assays, the most metastatic cells now showed the greatest linear speed. We conclude that traction stress, adhesion strength and rate of migration do indeed change as tumor cells progress in metastatic capacity and do so in a dimension-sensitive manner

The establishment of implanted VX2 liver tumor model in rabbits and discussion on superselective left hepatic arterial catheterization with micro-catheter technique via femoral artery

International Nuclear Information System (INIS)

Jiang Xiongying; Luo Rongguang; Huang Jinhua; Miao Bijian; Wang Yan

2011-01-01

Objective: To establish the implanted VX2 liver tumor model in rabbits and to discuss the feasibility and technical features of superselective left hepatic arterial catheterization by using micro-catheter through the femoral artery catheter sheath. Methods: Forty New Zealand white rabbits were inoculated with fragments of VX2 tumor into the medial left lobe of liver by using a 16G lumbar puncture needle through laparotomy route. Two weeks later, all the rabbits were proved to be successfully inoculated with liver neoplasm on CT scanning. Then, the catheter sheath was inserted into one of the femoral arteries, which was followed by celiac artery angiography and left hepatic artery catheterization with a micro-catheter under DSA guidance in order to evaluate the main branches of celiac artery and the imaging manifestations of VX2 liver tumor. After that, some scheduled interventional experiments were carried out. Results: Imaging examination and histopathologic study showed that the successful rate of implanted rabbit VX2 liver tumor was 100% (40/40). And the successful rate of the catheter sheath inserted to femoral artery was 97.5% (39/40). The successful rate of celiac artery, gastro-hepatic artery, common hepatic artery, proper hepatic artery and left hepatic artery catheterizations was 100% (39/39), 100% (39/39), 100% (39/39), 94.9% (37/39) and 71.2% (28/39) respectively. Conclusion: To implant tumor tissue mass through laparotomy is a stable and reliable method to establish rabbit VX2 liver tumor model. The insertion of micro-catheter through rabbit femoral catheter sheath approach is a convenient and simple technique to be carried out for the left hepatic artery catheterization and it can efficiently solve the technical difficulties when performing the interventional treatment of the rabbit VX2 hepatic tumor via left hepatic artery approach. (authors)

Metastatic neoplasms of the central nervous system

International Nuclear Information System (INIS)

Fenner, W.R.

1990-01-01

Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of ''metastatic neoplasm.'' In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed

Primary hepatic pheochromocytoma

International Nuclear Information System (INIS)

Rimmelin, A.; Hartheiser, M.; Gangi, A.; Welsch, M.; Jeung, M.Y.; Jaeck, D.; Tongio, J.; Dietemann, J.L.

1996-01-01

Pheochromocytomas are uncommon tumors that represent a potentially curable cause of hypertension. They are usually located in the adrenal glands, but 10% arise from extra-adrenal sites, located along the paravertebral sympathetic chains. We report a case of primary hepatic pheochromocytoma responsible for a severe hypertension in a 24-year-old man. Echotomography showed a lightly heterogeneous mass located in the segment 8 of the liver. Iodine 131 -metaiodobenzylguanidine scintigraphy showed a large hepatic concentration of the tracer and no other localization. This tumor appeared highly vascularized on enhanced CT scan and on aortic angiography. Magnetic resonance imaging revealed a hepatic tumor with a high signal intensity on T2-weighted images and with a signal isointense to the liver on T1-weighted images. The hepatic venous sampling contained the highest catecholamine level, whereas the adrenal venous samping was normal. After surgical resection of the hepatic tumor, the tension level and catecholamines plasmatic level normalized. No recurrent symptoms appeared during a 3-year follow-up. (orig.)

Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

Directory of Open Access Journals (Sweden)

VandenBerg Scott R

2010-04-01

Full Text Available Abstract Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3% cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients

Science.gov (United States)

Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai-Ming, Jr.; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

2016-04-01

Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had marker for the non-metastatic CRC patients who are at high risk of early recurrence.

Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma

Directory of Open Access Journals (Sweden)

Alvarez-Downing Melissa M

2012-06-01

Full Text Available Abstract Background Adoptive cell therapy (ACT with tumor-infiltrating lymphocytes (TIL in patients with metastatic melanoma has been reported to have a 56% overall response rate with 20% complete responders. To increase the availability of this promising therapy in patients with advanced melanoma, a minimally invasive approach to procure tumor for TIL generation is warranted. Methods A feasibility study was performed to determine the safety and efficacy of laparoscopic liver resection to generate TIL for ACT. Retrospective review of a prospectively maintained database identified 22 patients with advanced melanoma and visceral metastasis (AJCC Stage M1c who underwent laparoscopic liver resection between 1 October 2005 and 31 July 2011. The indication for resection in all patients was to receive postoperative ACT with TIL. Results Twenty patients (91% underwent resection utilizing a closed laparoscopic technique, one required hand-assistance and another required conversion to open resection. Median intraoperative blood loss was 100 mL with most cases performed without a Pringle maneuver. Median hospital stay was 3 days. Three (14% patients experienced a complication from resection with no mortality. TIL were generated from 18 of 22 (82% patients. Twelve of 15 (80% TIL tested were found to have in vitro tumor reactivity. Eleven patients (50% received the intended ACT. Two patients were rendered no evidence of disease after surgical resection, with one undergoing delayed ACT with generated TIL after relapse. Objective tumor response was seen in 5 of 11 patients (45% who received TIL, with one patient experiencing an ongoing complete response (32+ months. Conclusions Laparoscopic liver resection can be performed with minimal morbidity and serve as an effective means to procure tumor to generate therapeutic TIL for ACT to patients with metastatic melanoma.

Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor Alpha Therapy for the Treatment of Crohn's Disease

Directory of Open Access Journals (Sweden)

Tetsuya Ishida

2014-01-01

Full Text Available We report a 45-year-old female patient who developed acute hepatic disorder during anti-tumor necrosis factor α therapy for the treatment of Crohn's disease (CD. She was diagnosed as colonic CD and placed on infliximab (IFX. She was negative for hepatitis B surface antigen at the initiation of IFX therapy, but developed acute hepatitis after the 30th administration of IFX 4 years and 1 month after the first administration. She was suspected to have had occult hepatitis B virus infection before IFX therapy, and de novo hepatitis B was considered the most likely diagnosis. Hepatitis subsided after discontinuation of anti-tumor necrosis factor α therapy and initiation of treatment with entecavir. She started to receive adalimumab to prevent relapse of CD. She has continued maintenance therapy with entecavir and adalimumab and has since been asymptomatic. As de novo hepatitis B may be fatal, virological testing for hepatitis B is essential for patients who are being considered for treatment that may weaken the immune system.

Impact of additional SPECT in bone scanning in tumor patients with suspected metastatic bone disease

International Nuclear Information System (INIS)

Apostolova, I.; Goelcuek, E.; Buchert, R.; Brenner, W.; Bohuslavizki, K.H.

2009-01-01

The aim of this study was to investigate the additional value of single-photon emission computed tomography (SPECT) for patient staging compared to planar bone scanning in an unselected cohort of cancer patients. The study included 271 consecutive tumor patients in whom planar imaging and two-bed position SPECT of the spine and the pelvis had been performed. Retrospective image interpretation was performed independently for planar and SPECT scans. Findings were categorized as 'benign', 'equivocal', or malignant' on a lesion base, and as 'no metastatic disease', 'equivocal', or metastatic disease' on a patient base. Four hundred and forty seven lesions were detected by SPECT. Missing of lesions in planar images was rare (4.3% of all SPECT lesions). Planar findings differed from SPECT findings in 149 lesions (33.3%). Most of these 'inconsistent' lesions were rated as equivocal in the planar images but benign (14.5% of all lesions) or malignant (11.0%) by SPECT. On a patient base, 81.6% of patients with planar equivocal staging were classified as either benign (55.3%) or malignant (26.3%) by SPECT. Patients definitively staged as 'no metastatic disease' or 'metastatic disease' in planar images were staged differently by SPECT in only 3.7% of cases (up-staging in 2.6% and down-staging in 1.1%). Single-photon emission computed tomography changed a definite staging as based on planar images in less than 4% of the patients. In patients with planar equivocal staging, however, SPECT allowed a definite diagnosis in more than 80% of these cases, and, thus, should be performed routinely in patients with equivocal findings. (author)

Characteristics and Patterns of Metastatic Disease from Chordoma

Directory of Open Access Journals (Sweden)

Victoria A. Young

2015-01-01

Full Text Available Chordoma is a rare, slow-growing malignant tumor arising from notochordal remnants. A retrospective review of patient records at two major referral centers was undertaken to assess the incidence, location, and prognostic factors of metastatic disease from chordoma. 219 patients with chordoma (1962–2009 were identified. 39 patients (17.8% developed metastatic disease, most frequently to lung (>50%. Median survival from the time of initial diagnosis was 130.4 months for patients who developed metastatic disease and 159.3 months for those who did not (P=0.05. Metastatic disease was most common in the youngest patients (P=0.07, and it was 2.5 times more frequent among patients with local recurrence (26.3% than in those without (10.8% (P=0.003. Patient survival with metastatic disease was highly variable, and it was dependent on both the location of the tumor primary and the site of metastasis. Metastasis to distal bone was the most rapid to develop and had the worst prognosis.

A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells

Science.gov (United States)

Yu, Shu-Han; Zheng, Qizhi; Esopi, David; Macgregor-Das, Anne; Luo, Jun; Antonarakis, Emmanuel S.; Drake, Charles G.; Vessella, Robert; Morrissey, Colm; De Marzo, Angelo M.; Sfanos, Karen S.

2015-01-01

Correlative human studies suggest that the pleiotropic cytokine interleukin-6 (IL6) contributes to the development and/or progression of prostate cancer. However, the source of IL6 production in the prostate microenvironment in patients has yet to be determined. The cellular origin of IL6 in primary and metastatic prostate cancer was examined in formalin-fixed, paraffin-embedded (FFPE) tissues using a highly sensitive and specific chromogenic in situ hybridization (CISH) assay that underwent extensive analytical validation. Quantitative RT-PCR (q-RT-PCR) showed that benign prostate tissues often had higher expression of IL6 mRNA than matched tumor specimens. CISH analysis further indicated that both primary and metastatic prostate adenocarcinoma cells do not express IL6 mRNA. IL6 expression was highly heterogeneous across specimens and was nearly exclusively restricted to the prostate stromal compartment – including endothelial cells and macrophages among other cell types. The number of IL6-expressing cells correlated positively with the presence of acute inflammation. In metastatic disease, tumor cells were negative in all lesions examined and IL6 expression was restricted to endothelial cells within the vasculature of bone metastases. Finally, IL6 was not detected in any cells in soft tissue metastases. These data suggest that, in prostate cancer patients, paracrine rather than autocrine IL6 production is likely associated with any role for the cytokine in disease progression. PMID:26048576

FNAB of metastatic lesions with special reference to clinicopathological analysis of primary site in cases of epithelial and non-epithelial tumors

Directory of Open Access Journals (Sweden)

Shamshad Ahmad

2011-01-01

Conclusion: The most critical aspect of the evaluation of metastatic cases is the accurate pathologic assessment of the malignant tissues in conjunction with pertinent clinical data. Such close collaboration between the clinician and the pathologist may maximize the diagnostic potential in treatable primary tumors.

Metastasis 'systems' biology: how are macro-environmental signals transmitted into microenvironmental cues for disseminated tumor cells?

Science.gov (United States)

Grzelak, Candice Alexandra; Ghajar, Cyrus Michael

2017-10-01

Disseminated breast tumor cells reside on or near stable microvascular endothelium. Currently, the cues that disrupt DTC dormancy and facilitate outgrowth are largely unknown. This article explores the hypothesis that specific patient lifestyle exposures (e.g., alcohol abuse) may disrupt the microenvironments that maintain disseminated tumor cell (DTC) dormancy in a tissue-specific fashion. We suggest that such exposures are 'transmitted' to the dormant niche in the form of injury. Thus, we discuss the relationship between wound healing and metastasis using liver as an example to illustrate how injury steers the phenotype of liver endothelium and perivascular hepatic stellate cells to a potentially pro-metastatic one. We posit further that non-steroidal anti-inflammatory drugs (NSAIDs) - recently shown to prevent metastatic relapse - may act by preserving the dormant niche. We conclude by suggesting that maintenance of the dormant niche - either through patient lifestyle or via development of therapeutics that mimic local molecular cues/responses that coincide with a healthy lifestyle - is a means to prevent metastatic relapse, and should be the subject of far greater research. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

Energy Technology Data Exchange (ETDEWEB)

Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C. (Univ. of California, San Francisco (USA))

1990-06-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

International Nuclear Information System (INIS)

Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C.

1990-01-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection

Cancer stemness and metastatic potential of the novel tumor cell line K3: an inner mutated cell of bone marrow-derived mesenchymal stem cells.

Science.gov (United States)

Qian, Hui; Ding, Xiaoqing; Zhang, Jiao; Mao, Fei; Sun, Zixuan; Jia, Haoyuan; Yin, Lei; Wang, Mei; Zhang, Xu; Zhang, Bin; Yan, Yongmin; Zhu, Wei; Xu, Wenrong

2017-06-13

Mesenchymal stem cells (MSCs) transplantation has been used for therapeutic applications in various diseases. Here we report MSCs can malignantly transform in vivo. The novel neoplasm was found on the tail of female rat after injection with male rat bone marrow-derived MSCs (rBM-MSCs) and the new tumor cell line, K3, was isolated from the neoplasm. The K3 cells expressed surface antigens and pluripotent genes similar to those of rBM-MSCs and presented tumor cell features. Moreover, the K3 cells contained side population cells (SP) like cancer stem cells (CSCs), which might contribute to K3 heterogeneity and tumorigenic capacity. To investigate the metastatic potential of K3 cells, we established the nude mouse models of liver and lung metastases and isolated the corresponding metastatic cell lines K3-F4 and K3-B6. Both K3-F4 and K3-B6 cell lines with higher metastatic potential acquired more mesenchymal and stemness-related features. Epithelial-mesenchymal transition is a potential mechanism of K3-F4 and K3-B6 formation.

Metastatic Mantle Cell Lymphoma to the Pituitary Gland: Case Report and Literature Review

Directory of Open Access Journals (Sweden)

Arthur Wang

2016-01-01

Full Text Available We present an unusual case of a metastatic mantle cell lymphoma (MCL to the pituitary gland. The patient had a known history of MCL for which she previously received chemotherapy. She presented with new-onset diplopia and confusion, and reported a history of progressive vision blurriness associated with headache, nausea, and vomiting. MRI of the brain showed an enhancing lesion within the sella turcica involving the cavernous sinuses bilaterally, extending into Meckel's cave on the left, and abutting the optic nerves bilaterally. Following surgical excision, histopathology revealed the tumor to be a MCL. Metastatic pituitary tumors are rare and have been estimated to make up 1% of tumors discovered in the sellar region. The two most common secondary metastatic lesions to the sella are breast and lung carcinoma followed by prostate, renal cell, and gastrointestinal carcinoma. Metastatic lymphoma to the pituitary gland is especially rare and is estimated to constitute 0.5% of all metastatic tumors to the sella turcica. To our knowledge, this is the first reported case of MCL metastasizing to the pituitary gland.

The key role of extracellular vesicles in the metastatic process.

Science.gov (United States)

Zhao, Hongyun; Achreja, Abhinav; Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Nagrath, Deepak; Fais, Stefano

2018-01-01

Extracellular vesicles (EVs), including exosomes, have a key role in the paracrine communication between organs and compartments. EVs shuttle virtually all types of biomolecules such as proteins, lipids, nucleic acids, metabolites and even pharmacological compounds. Their ability to transfer their biomolecular cargo into target cells enables EVs to play a key role in intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration. This has led to the emergence of EVs as a key player in tumor growth and metastasis through the formation of "tumor niches" in target organs. Recent data have also been shown that EVs may transform the microenvironment of primary tumors thus favoring the selection of cancer cells with a metastatic behavior. The release of EVs from resident non-malignant cells may contribute to the metastatic processes as well. However, cancer EVs may induce malignant transformation in resident mesenchymal stem cells, suggesting that the metastatic process is not exclusively due to circulating tumor cells. In this review, we outline and discuss evidence-based roles of EVs in actively regulating multiple steps of the metastatic process and how we can leverage EVs to impair metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

B cells and ectopic follicular structures: novel players in anti-tumor programming with prognostic power for patients with metastatic colorectal cancer.

Directory of Open Access Journals (Sweden)

Anastasia Meshcheryakova

Full Text Available Remarkably limited information is available about biological mechanisms that determine the disease entity of metastatic colorectal cancer in the liver (CRCLM with no good clinical parameters to estimate prognosis. For the last few years, understanding the relationship between tumor characteristics and local immune response has gained increasing attention. Given the multifaceted roles of B-cell-driven responses, we aimed to elucidate the immunological imprint of B lymphocytes at the metastatic site, the interrelation with macrophages, and their prognostic relevance. Here we present novel algorithm allowing to assess a link between the local patient-specific immunological capacity and clinical outcome. The microscopy-based imaging platform was used for automated scanning of large-scale tissue sections and subsequent qualitative and quantitative analyses of immune cell subtypes using lineage markers and single-cell recognition strategy. Results indicate massive infiltration of CD45-positive leukocytes confined to the metastatic border. We report for the first time the accumulation of CD20-positive B lymphocytes at the tumor-liver interface comprising the major population within the large CD45-positive aggregates. Strikingly, functionally active, activation-induced cytidine deaminase (AID-positive ectopic lymphoid structures were found to be assembled within the metastatic margin. Furthermore, the CD20-based data set revealed a strong prognostic power: patients with high CD20 content and/or ectopic follicles had significantly lower risk for disease recurrence as revealed by univariate analysis (p<0.001 for both and in models adjusted for clinicopathological variables (p<0.001 and p = 0.01, respectively, and showed prolonged overall survival. In contrast, CD68 staining-derived data set did not show an association with clinical outcome. Taken together, we nominate the magnitude of B lymphocytes, including those organized in ectopic follicles, as

Hepatic natural killer cells exclusively kill splenic/blood natural killer-resistant tumor cells by the perforin/granzyme pathway

NARCIS (Netherlands)

Vermijlen, David; Luo, Dianzhong; Froelich, Christopher J.; Medema, Jan Paul; Kummer, Jean Alain; Willems, Erik; Braet, Filip; Wisse, Eddie

2002-01-01

Hepatic natural killer (NK) cells are located in the liver sinusoids adherent to the endothelium. Human and rat hepatic NK cells induce cytolysis in tumor cells that are resistant to splenic or blood NK cells. To investigate the mechanism of cell death, we examined the capacity of isolated, pure

Assessment of the role of circulating breast cancer cells in tumor formation and metastatic potential using in vivo flow cytometry

Science.gov (United States)

Hwu, Derrick; Boutrus, Steven; Greiner, Cherry; Dimeo, Theresa; Kuperwasser, Charlotte; Georgakoudi, Irene

2011-04-01

The identification of breast cancer patients who will ultimately progress to metastatic disease is of significant clinical importance. The quantification and assessment of circulating tumor cells (CTCs) has been proposed as one strategy to monitor treatment effectiveness and disease prognosis. However, CTCs have been an elusive population of cells to study because of their small number and difficulties associated with isolation protocols. In vivo flow cytometry (IVFC) can overcome these limitations and provide insights in the role these cells play during primary and metastatic tumor growth. In this study, we used two-color IVFC to examine, for up to ten weeks following orthotopic implantation, changes in the number of circulating human breast cells expressing GFP and a population of circulating hematopoietic cells with strong autofluorescence. We found that the number of detected CTCs in combination with the number of red autofluorescent cells (650 to 690 nm) during the first seven days following implantation was predictive in development of tumor formation and metastasis eight weeks later. These results suggest that the combined detection of these two cell populations could offer a novel approach in the monitoring and prognosis of breast cancer progression, which in turn could aid significantly in their effective treatment.

Predictive factors of symptomatic radiation pneumonitis in primary and metastatic lung tumors treated with stereotactic ablative body radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Kim, Kang Pyo; Lee, Jeong Shim; Cho, Yeona; Chung, Seung Yeun; Lee, Jason Joon Bock; Lee, Chang Geol; Cho, Jae Ho [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2017-06-15

Although stereotactic ablative body radiotherapy (SABR) is widely used therapeutic technique, predictive factors of radiation pneumonitis (RP) after SABR remain undefined. We aimed to investigate the predictive factors affecting RP in patients with primary or metastatic lung tumors who received SABR. From 2012 to 2015, we reviewed 59 patients with 72 primary or metastatic lung tumors treated with SABR, and performed analyses of clinical and dosimetric variables related to symptomatic RP. SABR was delivered as 45–60 Gy in 3–4 fractions, which were over 100 Gy in BED when the α/β value was assumed to be 10. Tumor volume and other various dose volume factors were analyzed using median value as a cutoff value. RP was graded per the Common Terminology Criteria for Adverse Events v4.03. At the median follow-up period of 11 months, symptomatic RP was observed in 13 lesions (12 patients, 18.1%), including grade 2 RP in 11 lesions and grade 3 in 2 lesions. Patients with planning target volume (PTV) of ≤14.35 mL had significantly lower rates of symptomatic RP when compared to others (8.6% vs. 27%; p = 0.048). Rates of symptomatic RP in patients with internal gross tumor volume (iGTV) >4.21 mL were higher than with ≤4.21 mL (29.7% vs. 6.1%; p = 0.017). The incidence of symptomatic RP following treatment with SABR was acceptable with grade 2 RP being observed in most patients. iGTV over 4.21 mL and PTV of over 14.35 mL were significant predictive factors related to symptomatic RP.

Radiofrequency thermal ablation of malignant hepatic tumors: post-ablation syndrome

International Nuclear Information System (INIS)

Choi, Jung Bin; Rhim, Hyunchul; Kim, Yongsoo; Koh, Byung Hee; Cho, On Koo; Seo, Heung Suk; Lee, Seung Ro

2000-01-01

To evaluate post-ablation syndrome after radiofrequency thermal ablation of malignant hepatic tumors. Forty-two patients with primary (n=3D29) or secondary (n=3D13) hepatic tumors underwent radiofrequency thermal ablation. A total of 65 nodules ranging in size from 1.1 to 5.0 (mean, 3.1) cm were treated percutaneously using a 50W RF generator with 15G expandable needle electrodes. We retrospectively evaluated the spectrum of post-ablation syndrome including pain, fever (≥3D 38 deg C), nausea, vomiting, right shoulder pain, and chest discomfort according to frequency, intensity and duration, and the findings were correlated with tumor location and number of ablations. We also evaluated changes in pre-/post-ablation serum aminotransferase (ALT/AST) and prothrombin time, and correlated these findings with the number of ablations. Post-ablation syndrome was noted in 29 of 42 patients (69.0%), and most symptoms improved with conservative treatment. The most important of these were abdominal plan (n=3D20, 47.6%), fever (n=3D8, 19.0%), and nausea (n=3D7, 16.7%), and four of 42 (9.5%) patients complained of severe pain. The abdominal pain lasted from 3 hours to 5.5 days (mean; 20.4 hours), the fever from 6 hours to 5 days (mean; 63.0 hours). And the nausea from 1 hours to 4 days (mean; 21.0 hours). Other symptoms were right shoulder pain (n=3D6, 14.3%), chest discomfort (n=3D3, 7.1%), and headache (n=3D3, 7.1%). Seventeen of 20 patients (85%) with abdominal pain had subcapsular tumor of the liver. There was significant correlation between pain, location of the tumor, and a number of ablations. After ablation, ALT/AST was elevated more than two-fold in 52.6%/73.7% of patients, respectively but there was no significant correlation with the number of ablation. Post-ablation syndrome is a frequent and tolerable post-procedural process after radiofrequency thermal ablation. The spectrum of this syndrome provides a useful guideline for the post-ablation management. (author)

Effect of induced hyperglycemia on metastatic spreading in Lewis lung carcinoma

International Nuclear Information System (INIS)

Shmakova, N.L.; Fomenkova, T.E.; Fadeeva, T.A.

1991-01-01

The effect of induced hyperglycemia on the intensity of metastatic dissemination of Lewis lung carcinoma was investigated in experiments on mice. Neither long-, nor short-term hyperglycemia, induced at different phases of dissemination, influenced the intensity of metastatic spreading, primary tumor growth, the time of appearance of metastases, and the average life duration of tumor-bearing animals

Absence of mutations in the coding sequence of the potential tumor suppressor 3pK in metastatic melanoma

Directory of Open Access Journals (Sweden)

Houben Roland

2005-12-01

Full Text Available Abstract Background Activation of Ras or Raf contributes to tumorigenesis of melanoma. However, constitutive Raf activation is also a characteristic of the majority of benign melanocytic nevi and high intensity signaling of either Ras or Raf was found to induce growth inhibition and senescence rather than transformation. Since the chromosome 3p kinase (3pK is a target of the Ras/Raf/Mek/Erk signaling pathway which antagonizes the function of the oncogene and anti-differentiation factor Bmi-1, 3pK may function as a tumor suppressor in tumors with constitutive Ras/Raf activation. Consequently, we tested whether inactivating 3pK mutations are present in melanoma. Methods 30 metastatic melanoma samples, which were positive for activating mutations of either BRaf or NRas, were analyzed for possible mutations in the 3pk gene. The 10 coding exons and their flanking intron sequences were amplified by PCR and direct sequencing of the PCR products was performed. Results This analysis revealed that besides the presence of some single nucleotide polymorphisms in the 3pk gene, we could not detect any possible loss of function mutation in any of these 30 metastatic melanoma samples selected for the presence of activating mutations within the Ras/Raf/Mek/Erk signaling pathway. Conclusion Hence, in melanoma with constitutively active Ras/Raf inactivating mutations within the 3pk gene do not contribute to the oncogenic phenotype of this highly malignant tumor.

Metastatic clear-cell hidradenocarcinoma of the vulva.

Science.gov (United States)

Messing, M J; Richardson, M S; Smith, M T; King, L; Gallup, D G

1993-02-01

Clear-cell hidradenocarcinoma is a malignant tumor of sweat gland origin. It is most often found on the trunk, head, and extremities. This case report describes a rare occurrence of this tumor on the vulva of a young woman. The discovery of metastatic disease reflects the potentially aggressive nature of this tumor.

Laser-induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection.

Science.gov (United States)

Isbert, Christoph; Ritz, Jörg-Peter; Roggan, André; Schuppan, Detlef; Ajubi, Navid; Buhr, Heinz Johannes; Hohenberger, Werner; Germer, Christoph-Thomas

2007-01-01

Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24-96 hours and 14 days after intervention. Volumes of the untreated tumors prior to intervention were 38+/-8 mm(3) in group I (laser), 39 +/- 7 mm(3) in group II (resection), and 42 +/- 12 mm(3) in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor+/-SEM volume of untreated tumor in group I (laser) [223 +/- 36] was smaller than in group II (resection) [1233.28 +/- 181.52; P tumor growth in comparison to hepatic resection. Accelerated tumor growth after hepatic resection is associated with higher mRNA level of HGF and reduced tumor growth after LITT with higher mRNA level of CTGF. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT. (c) 2006 Wiley-Liss, Inc.

Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

LENUS (Irish Health Repository)

Dowdall, J F

2012-02-03

The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

Differential inhibition of ex-vivo tumor kinase activity by vemurafenib in BRAF(V600E and BRAF wild-type metastatic malignant melanoma.

Directory of Open Access Journals (Sweden)

Andliena Tahiri

Full Text Available Treatment of metastatic malignant melanoma patients harboring BRAF(V600E has improved drastically after the discovery of the BRAF inhibitor, vemurafenib. However, drug resistance is a recurring problem, and prognoses are still very bad for patients harboring BRAF wild-type. Better markers for targeted therapy are therefore urgently needed.In this study, we assessed the individual kinase activity profiles in 26 tumor samples obtained from patients with metastatic malignant melanoma using peptide arrays with 144 kinase substrates. In addition, we studied the overall ex-vivo inhibitory effects of vemurafenib and sunitinib on kinase activity status.Overall kinase activity was significantly higher in lysates from melanoma tumors compared to normal skin tissue. Furthermore, ex-vivo incubation with both vemurafenib and sunitinib caused significant decrease in phosphorylation of kinase substrates, i.e kinase activity. While basal phosphorylation profiles were similar in BRAF wild-type and BRAF(V600E tumors, analysis with ex-vivo vemurafenib treatment identified a subset of 40 kinase substrates showing stronger inhibition in BRAF(V600E tumor lysates, distinguishing the BRAF wild-type and BRAF(V600E tumors. Interestingly, a few BRAF wild-type tumors showed inhibition profiles similar to BRAF(V600E tumors. The kinase inhibitory effect of vemurafenib was subsequently analyzed in cell lines harboring different BRAF mutational status with various vemurafenib sensitivity in-vitro.Our findings suggest that multiplex kinase substrate array analysis give valuable information about overall tumor kinase activity. Furthermore, intra-assay exposure to kinase inhibiting drugs may provide a useful tool to study mechanisms of resistance, as well as to identify predictive markers.

Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.

Directory of Open Access Journals (Sweden)

Ketao Jin

Full Text Available The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.

Esophageal Large-Cell Neuroendocrine Carcinoma with Inconsistent Response to Treatment in the Primary and Metastatic Lesions

Directory of Open Access Journals (Sweden)

Takashi Tomiyama

2018-05-01

Full Text Available Esophageal large-cell neuroendocrine carcinoma (NEC is a rare malignant tumor that is characterized by high-grade malignancy and a poor prognosis. However, the rarity of esophageal NEC has prevented the development of an established treatment, and no reports have described a discrepancy in the effectiveness of cisplatin plus irinotecan between primary and metastatic lesions. A 43-year-old Japanese man was referred to our hospital with refractory epigastralgia. A previous gastrointestinal endoscopy had revealed a 50-mm type 2 tumor in the abdominal esophagus. The pathological findings indicated poorly differentiated squamous cell carcinoma. Contrast-enhanced computed tomography revealed a metastatic liver tumor. One cycle of fluorouracil and cisplatin was not effective, and endoscopy was repeatedly performed. The pathological findings indicated a large-cell malignant tumor with tumor cells that were positive for CD56, synaptophysin, and Ki-67 (> 80%. Based on a diagnosis of esophageal large-cell NEC with a metastatic liver tumor, the patient received cisplatin plus irinotecan biweekly. After 4 months, computed tomography revealed marked shrinkage of the metastatic tumor, but the patient complained of dysphagia. Endoscopy revealed enlargement of the primary tumor, which was then treated using radiotherapy plus fluorouracil and cisplatin. The primary tumor subsequently shrank, and the patient’s symptoms were relieved, but the metastatic tumor grew. Thus, chemoradiotherapy could be an option for managing a primary esophageal large-cell NEC that does not respond to chemotherapy alone. However, the possibility of an inconsistent response to therapy in primary and metastatic lesions should be considered.

Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

Directory of Open Access Journals (Sweden)

Jianjin Huang

Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration*

Science.gov (United States)

Piao, Chunmei; Cai, Lun; Qiu, Shulan; Jia, Lixin; Song, Wenchao; Du, Jie

2015-01-01

Complement 5a (C5a), a potent immune mediator generated by complement activation, promotes tumor growth; however, its role in tumor metastasis remains unclear. We demonstrate that C5a contributes to tumor metastases by modulating tumor inflammation in hepatic metastases of colon cancer. Colon cancer cell lines generate C5a under serum-free conditions, and C5a levels increase over time in a murine syngeneic colon cancer hepatic metastasis model. Furthermore, in the absence of C5a receptor or upon pharmacological inhibition of C5a production with an anti-C5 monoclonal antibody, tumor metastasis is severely impaired. A lack of C5a receptor in colon cancer metastatic foci reduces the infiltration of macrophages, neutrophils, and dendritic cells, and the role for C5a receptor on these cells were further verified by bone marrow transplantation experiments. Moreover, C5a signaling increases the expression of the chemokine monocyte chemoattractant protein-1 and the anti-inflammatory molecules arginase-1, interleukin 10, and transforming growth factor β, but is inversely correlated with the expression of pro-inflammatory molecules, which suggests a mechanism for the role of C5a in the inflammatory microenvironment required for tumor metastasis. Our results indicate a new and potentially promising therapeutic application of complement C5a inhibitor for the treatment of malignant tumors. PMID:25739439

Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

International Nuclear Information System (INIS)

Rangwala, Fatima; Williams, Kevin P; Smith, Ginger R; Thomas, Zainab; Allensworth, Jennifer L; Lyerly, H Kim; Diehl, Anna Mae; Morse, Michael A; Devi, Gayathri R

2012-01-01

Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO) in combination with sorafenib or fluorouracil (5-FU), in both hepatic tumor cells and stromal cells. Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC 50 : 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC 50 : 11.8 μM in LX2; 9.9 μM in HepG2). In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr) drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC)

Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

Directory of Open Access Journals (Sweden)

Rangwala Fatima

2012-09-01

Full Text Available Abstract Background Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO in combination with sorafenib or fluorouracil (5-FU, in both hepatic tumor cells and stromal cells. Methods Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Results Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC50: 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC50: 11.8 μM in LX2; 9.9 μM in HepG2. In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. Conclusions ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC.

Sonographic findings of space occupying lesions in liver

Energy Technology Data Exchange (ETDEWEB)

Kim, In One; Choi, B I; Kim, J W [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1982-12-15

Gray scale ultrasonography is used with increasing frequency for the detection and characterization of hepatic space occupying lesions. Authors analyzed sonographic findings of 73 cases of hepatic space occupying lesions,which had been confirmed histologically or diagnosed clinically. The results were summarized as follows: 1. Most common sonographic pattern of hepatic neoplasms was well-defined increased echogenic mass. No significant sonographic difference was noted between primary and metastatic tumor. Splenomegaly and distortion of hepatic echoes favored hepatocellular carcinoma, and multiplicity favored metastatic tumor. 2. Most common sonographic pattern of hepatic abscess was well-defined decreased echogenecity or echoless cystic lesion containing fine low level echoes with posterior enhancement. 3. Hepatic cyst showed sharply defined echoless cystic lesion with strong posterior enhancement

Cell Free DNA of Tumor Origin Induces a 'Metastatic' Expression Profile in HT-29 Cancer Cell Line.

Directory of Open Access Journals (Sweden)

István Fűri

Full Text Available Epithelial cells in malignant conditions release DNA into the extracellular compartment. Cell free DNA of tumor origin may act as a ligand of DNA sensing mechanisms and mediate changes in epithelial-stromal interactions.To evaluate and compare the potential autocrine and paracrine regulatory effect of normal and malignant epithelial cell-related DNA on TLR9 and STING mediated pathways in HT-29 human colorectal adenocarcinoma cells and normal fibroblasts.DNA isolated from normal and tumorous colonic epithelia of fresh frozen surgically removed tissue samples was used for 24 and 6 hour treatment of HT-29 colon carcinoma and HDF-α fibroblast cells. Whole genome mRNA expression analysis and qRT-PCR was performed for the elements/members of TLR9 signaling pathway. Immunocytochemistry was performed for epithelial markers (i.e. CK20 and E-cadherin, DNA methyltransferase 3a (DNMT3a and NFκB (for treated HDFα cells.Administration of tumor derived DNA on HT29 cells resulted in significant (p<0.05 mRNA level alteration in 118 genes (logFc≥1, p≤0.05, including overexpression of metallothionein genes (i.e. MT1H, MT1X, MT1P2, MT2A, metastasis-associated genes (i.e. TACSTD2, MACC1, MALAT1, tumor biomarker (CEACAM5, metabolic genes (i.e. INSIG1, LIPG, messenger molecule genes (i.e. DAPP, CREB3L2. Increased protein levels of CK20, E-cadherin, and DNMT3a was observed after tumor DNA treatment in HT-29 cells. Healthy DNA treatment affected mRNA expression of 613 genes (logFc≥1, p≤0.05, including increased expression of key adaptor molecules of TLR9 pathway (e.g. MYD88, IRAK2, NFκB, IL8, IL-1β, STING pathway (ADAR, IRF7, CXCL10, CASP1 and the FGF2 gene.DNA from tumorous colon epithelium, but not from the normal epithelial cells acts as a pro-metastatic factor to HT-29 cells through the overexpression of pro-metastatic genes through TLR9/MYD88 independent pathway. In contrast, DNA derived from healthy colonic epithelium induced TLR9 and STING signaling

Metastatic Lung Lesions as a Preferred Resection Site for Immunotherapy With Tumor Infiltrating Lymphocytes.

Science.gov (United States)

Ben-Avi, Ronny; Itzhaki, Orit; Simansky, David; Zippel, Dov; Markel, Gal; Ben Nun, Alon; Schachter, Jacob; Besser, Michal J

2016-06-01

Adoptive cell therapy with tumor infiltrating lymphocytes (TIL) yields 50% response rates in metastatic melanoma and shows promising clinical results in other solid tumors. Autologous TIL cultures are isolated from resected tumor tissue, expanded ex vivo to large numbers and reinfused to the preconditioned patient. In this prospective study, we validate the origin of the tumor biopsy and its effect on T-cell function and clinical response. One hundred forty-four patients underwent surgery and 79 patients were treated with TIL adoptive cell therapy. Cultures from lung tissue were compared with other origins. The success rate of establishing TIL culture from lung tissue was significantly higher compared with nonlung tissue (94% vs. 72%, respectively, P≤0.003). Lung-derived TIL cultures gave rise to higher cell numbers (P≤0.011) and exhibited increased in vitro antitumor reactivity. The average fold expansion for lung-derived TIL during a rapid expansion procedure was 1349±557 compared with 1061±473 for nonlung TIL (P≤0.038). Patients treated with TIL cultures of lung origin (compared with nonlung) had prolonged median overall survival (29 vs. 9.5 mo; P≤0.065). Given the remarkable advancement in minimally invasive thoracic surgery and the results of this study, we suggest efforts should be taken to resect lung metastasis rather than other sites to generate TIL cultures for clinical use.

Medical image of the week: metastatic testicular cancer

Directory of Open Access Journals (Sweden)

Debo M

2014-06-01

Full Text Available A 30 year-old man with metastatic embryonal testicular cancer was admitted to the hospital with severe abdominal pain. A contrast enhanced CT of the abdomen demonstrated large metastatic burden throughout the liver and the left adrenal gland (Figures 1 and 2. The mass arising from the left adrenal gland caused significant mass effect. The left kidney was compressed, though without hydronephrosis, and the spleen was displaced laterally. Renal and hepatic functions were preserved. His pain was controlled with opioids and oral steroids with significant improvement.

Diffusion-weighted magnetic resonance imaging in metastatic gastrointestinal stromal tumor (GIST) - A pilot study on the assessment of treatment response in comparison with 18F-FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Schmidt, Sabine; Koehli, Melanie; Meuli, Reto [Dept. of Radiology, Centre Hospitalier Universitaire Vaudois, Univ. of Lausanne, Lausanne (Switzerland)], e-mail: sabine.schmidt@chuv.ch; Dunet, Vincent; Prior, John O. [Dept. of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois, Uniausanne, Lausanne (Switzerland); Montemurro, Michael [Dept. of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Univ. of Lausanne, Lausanne (Switzerland)

2013-10-15

Background: Diffusion-weighted magnetic resonance imaging (MRI) is increasingly being used for assessing the treatment success in oncology, but the real clinical value needs to evaluated by comparison with other, already established, metabolic imaging techniques. Purpose: To prospectively evaluate the clinical potential of diffusion-weighted MRI with apparent diffusion coefficient (ADC) mapping for gastrointestinal stromal tumor (GIST) response to targeted therapy compared with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Material and Methods: Eight patients (mean age, 56{+-}11 years) known to have metastatic GIST underwent 18F-FDG PET/CT and MRI (T1Gd, DWI [b = 50,300,600], ADC mapping) simultaneously, before and after change in targeted therapy. MR and PET/CT examinations were first analyzed blindly. Second, PET/CT images were co-registered with T1Gd-MR images for lesion detection. Only 18F-FDG avid lesions were considered. Maximum standardized uptake value (SUV{sub max}) and the corresponding minimum ADC{sub min} were measured for the six largest lesions per patient, if any, on baseline and follow-up examinations. The relationship between changes in SUV{sub max} and ADCmin was analyzed (Spearman's correlation). Results: Twenty-four metastases (12 hepatic, 12 extra-hepatic) were compared on PET/CT and MR images. SUV{sub max} decreased from 7.7{+-}8.1 g/mL to 5.5{+-}5.4 g/mL (P = 0.20), while ADC{sub min} increased from 1.2{+-}0.3 X 10{sup -3}mm{sup 2}/s to 1.5{+-}0.3 X 10{sup -3}mm{sup 2}/s (P = 0.0002). There was a significant association between changes in SUV{sub max} and ADC{sub min} (rho = - 0.62, P = 0.0014), but not between changes in lesions size (P = 0.40). Conclusion: Changes in ADCmin correlated with the response of 18F-FDG avid GIST to targeted therapy. Thus, diffusion-weighted MRI may represent a radiation-free alternative for follow-up treatment for metastatic GIST patients.

Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

Science.gov (United States)

Snyder, Matthew; Bottiglieri, Sal; Almhanna, Khaldoun

2018-01-01

Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy. However, many significant questions remain as to which agent reflects best practice. Our review aimed to elucidate the benefit of adding bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer based on primary tumor location and a variety of other disease- and patient-related factors, addressing the paucity of evidence that currently exists in this area and contributing to current literature and clinical practices. The primary endpoints of the study were first Progression-Free Survival (PFS) and Overall Survival (OS). Secondary endpoints included best response to first- and second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS, cost of therapy, and an assessment of other patient- and disease-related factors affecting PFS and OS. While there were trends towards improved OS in patients with left-sided primary tumors (n=57) compared to those with right-sided disease (n=23), there were no significant differences between the two groups in either primary endpoint. While no differences were found for patients with left- or right- sided tumors stratified by add-on agent, these analyses were limited by the small number of patients receiving cetuximab with first-line therapy (n=4). However, the bevacizumab cohort (n=76) was sizable enough to provide ample data and produce clinically relevant results. Add-on therapy with bevacizumab in our study achieved impressive survival outcomes in both left-sided (median first PFS = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21

Changes in the peritumoral hypoperfusion area immediately after radiosurgery for metastatic brain tumor. Analysis using 3D-SPECT

Energy Technology Data Exchange (ETDEWEB)

Nemoto, Masaaki [Toho Univ., Tokyo (Japan). School of Medicine

2001-09-01

Sixteen patients with single metastatic brain tumor underwent SPECT using N-isopropyl-p-({sup 123}I) iodoamphetamine ({sup 123}I-IMP) before and after radiosurgery. Influence of treatment was evaluated using three-dimensional SPECT images, threshold-voxel graphs and changes in the volume of the peritumoral hypoperfusion area. A three-detector type scanner, the PRISM3000, was also used. SPECT scanning was performed for 30 minutes after intravenous administration of {sup 123}I-IMP with sequential scans every 1 minutes. The data obtained 16-30 minutes after administration were processed using a low-pass ramp filter, and three-dimensional SPECT images were constructed from these data using the Application Visualization System (AVS). Furthermore, a threshold-voxel graph was plotted and the volume of the peritumoral hypoperfusion area was calculated. SPECT was performed before radiosurgery, and 1 day, 1 week, and 1 month after, and these data were compared. Three-dimensional SPECT presented the area of peritumoral hypoperfusion as a deficit image and changes were evaluated visually. Threshold-voxel graphs were evaluated as follows: changes in voxels with a threshold of 40-50% indicated a hypoperfusion area, and changes in voxels with a threshold of 70-95% indicated a hyperperfusion area in the tumor side hemisphere. The volume of the peritumoral hypoperfusion area was calculated using the voxel difference between the tumor side and normal hemispheres. Our results showed that the peritumoral hypoperfusion area gradually decreased after an initial first-day increase following radiosurgery. Visual three-dimensional SPECT allowed us to monitor both the volume of the peritumoral hypoperfusion area of metastatic brain tumors after radiosurgery by means of a threshold-voxel graph and changes in the peritumoral hypoperfusion area. (author)

Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes.

Science.gov (United States)

Hallet, Julie; Law, Calvin How Lim; Cukier, Moises; Saskin, Refik; Liu, Ning; Singh, Simron

2015-02-15

An increased incidence of neuroendocrine tumors (NETs) has been reported worldwide, but the reasons underlying this rise have not been identified. By assessing patterns of metastatic presentation, this study sought to examine the epidemiologic characteristics of NETs and the contribution of early-stage detection to the rising incidence. A population-based retrospective cohort study was conducted with prospectively maintained databases linked at the Institute for Clinical Evaluative Sciences. Adult patients with a NET diagnosis from 1994 to 2009 in Ontario, Canada were included. The main outcomes included the overall and site-specific incidence, proportion of metastatic disease, overall survival (OS), and recurrence-free survival (RFS). Five thousand six hundred nineteen NET cases were identified. The incidence of NETs increased from 2.48 to 5.86 per 100,000 per year. Metastases were found in 20.8% at presentation and in another 38% after the initial diagnosis. The proportion of metastases at presentation decreased from 1994 to 2009 (from 29% to 13%). Therefore, although the incidence of all NETs increased, the overall incidence of metastases did not change (0.63-0.69 per 100,000 per year). The 10-year OS rate was 46.5%, and the RFS rate was 64.6%. In addition to the primary tumor site, independent predictors of worse OS included an advanced age (P incidence of NETs has markedly increased over the course of 15 years. This is the first study to provide evidence suggesting that the increase in the incidence of NETs may be due to increased detection. In addition to tumor characteristics, low income and rural residency portend worse survival for patients with NETs. © 2014 American Cancer Society.

Clinical manifestations and computed tomography of the pseudovascular form of metastatic brain tumor

International Nuclear Information System (INIS)

Kurimoto, Tadahisa; Mizuno, Makoto; Tani, Sadayasu; Miki, Kazuhito; Kawamura, Yasuo; Matsumura, Hiroshi

1982-01-01

Forty-two cases of metastatic brain tumor were subdivided into 3 groups (acute, subacute, and chronic) from their mode of the onset of symptoms and signs. The clinical symptoms and signs and the computed tomogram were all analyzed and compared with each other. The acute form was found in 14 cases (33%), of which 7% (3 cases) were seizures and 26% (11 cases) were acute neurological deficits, including hemorrhages from tumors (3 cases, 7%). There were no significant differences in their age, sex, or primary lesions. The characteristic course of the acute form, other than seizure and hemorrhage, involved acutely and progressively developing neurological symptoms, symptoms and signs of increased intracranial pressure were rare. In computed tomogram, the solitary metastasis in the parietal and occipital lesions was much more in the acute form than in other forms, and the perifocal low-density area showed a tendency to be larger than the other forms. In these cases, acute symptoms and signs appeared to occur easily when perifocal edema was joined in the above locations. The pathogenesis of acute neurological symptoms and signs other than seizure and hemorrhage is unclear. We suggest that the location of a tumor and peritumoral edema be important factors in causing acute symptoms and signs, but, in addition to that, abrupt hemodynamic changes in the peritumoral edema may also be of importance. (J.P.N.)

Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer.

Science.gov (United States)

Ma, Cynthia X; Bose, Ron; Gao, Feng; Freedman, Rachel A; Telli, Melinda L; Kimmick, Gretchen; Winer, Eric; Naughton, Michael; Goetz, Matthew P; Russell, Christy; Tripathy, Debu; Cobleigh, Melody; Forero, Andres; Pluard, Timothy J; Anders, Carey; Niravath, Polly Ann; Thomas, Shana; Anderson, Jill; Bumb, Caroline; Banks, Kimberly C; Lanman, Richard B; Bryce, Richard; Lalani, Alshad S; Pfeifer, John; Hayes, Daniel F; Pegram, Mark; Blackwell, Kimberly; Bedard, Philippe L; Al-Kateb, Hussam; Ellis, Matthew J C

2017-10-01

Purpose: Based on promising preclinical data, we conducted a single-arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2 mut nonamplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxicity, and circulating tumor DNA (ctDNA) HER2 mut detection. Experimental Design: Tumor tissue positive for HER2 mut was required for eligibility. Neratinib was administered 240 mg daily with prophylactic loperamide. ctDNA sequencing was performed retrospectively for 54 patients (14 positive and 40 negative for tumor HER2 mut ). Results: Nine of 381 tumors (2.4%) sequenced centrally harbored HER2 mut (lobular 7.8% vs. ductal 1.6%; P = 0.026). Thirteen additional HER2 mut cases were identified locally. Twenty-one of these 22 HER2 mut cases were estrogen receptor positive. Sixteen patients [median age 58 (31-74) years and three (2-10) prior metastatic regimens] received neratinib. The CBR was 31% [90% confidence interval (CI), 13%-55%], including one CR, one PR, and three SD ≥24 weeks. Median PFS was 16 (90% CI, 8-31) weeks. Diarrhea (grade 2, 44%; grade 3, 25%) was the most common adverse event. Baseline ctDNA sequencing identified the same HER2 mut in 11 of 14 tumor-positive cases (sensitivity, 79%; 90% CI, 53%-94%) and correctly assigned 32 of 32 informative negative cases (specificity, 100%; 90% CI, 91%-100%). In addition, ctDNA HER2 mut variant allele frequency decreased in nine of 11 paired samples at week 4, followed by an increase upon progression. Conclusions: Neratinib is active in HER2 mut , nonamplified MBC. ctDNA sequencing offers a noninvasive strategy to identify patients with HER2 mut cancers for clinical trial participation. Clin Cancer Res; 23(19); 5687-95. ©2017 AACR . ©2017 American Association for Cancer Research.

m-RNA mammaglobin expression in metastatic breast cancer patient at Medan city, Indonesia

Science.gov (United States)

Rimbun, S.; Siregar, Y.

2018-03-01

Breast cancer is the most common causes of women’s death in the world. Metastatic spread presents a major clinical problem in about 30% of the patients. The study aims to investigate the clinical reliability of mammaglobin mRNA as a marker of circulating cancer cells in breast cancer patients. The positivity of blood was analyzed in relation to clinical and pathological characteristics. This study was on 29 breast cancer patients (13 metastatic, 16 non- metastatic patients), where28 were invasive intraductal carcinoma type and 1 was invasive lobular carcinoma type. Breast cancer patients were according to the histologic grade into grade I (7 patients),grade II (6 patients) and grade III (15 patients). All individuals included in this study were subjected to detection of mammaglobin m-RNA of circulating tumor cells in peripheral blood using RT-PCR technique. Positivity for mammaglobin in blood samples was in 38% of patients with metastatic but not in the non-metastatic patients. The presence of mammaglobin correlated with metastatic tumor (P = 0.011). Mammaglobin overexpression in breast tissue was significantly positive in low-grade tumors (I and II).

Foretinib is effective therapy for metastatic sonic hedgehog medulloblastoma.

Science.gov (United States)

Faria, Claudia C; Golbourn, Brian J; Dubuc, Adrian M; Remke, Marc; Diaz, Roberto J; Agnihotri, Sameer; Luck, Amanda; Sabha, Nesrin; Olsen, Samantha; Wu, Xiaochong; Garzia, Livia; Ramaswamy, Vijay; Mack, Stephen C; Wang, Xin; Leadley, Michael; Reynaud, Denis; Ermini, Leonardo; Post, Martin; Northcott, Paul A; Pfister, Stefan M; Croul, Sidney E; Kool, Marcel; Korshunov, Andrey; Smith, Christian A; Taylor, Michael D; Rutka, James T

2015-01-01

Medulloblastoma is the most common malignant pediatric brain tumor, with metastases present at diagnosis conferring a poor prognosis. Mechanisms of dissemination are poorly understood and metastatic lesions are genetically divergent from the matched primary tumor. Effective and less toxic therapies that target both compartments have yet to be identified. Here, we report that the analysis of several large nonoverlapping cohorts of patients with medulloblastoma reveals MET kinase as a marker of sonic hedgehog (SHH)-driven medulloblastoma. Immunohistochemical analysis of phosphorylated, active MET kinase in an independent patient cohort confirmed its correlation with increased tumor relapse and poor survival, suggesting that patients with SHH medulloblastoma may benefit from MET-targeted therapy. In support of this hypothesis, we found that the approved MET inhibitor foretinib could suppress MET activation, decrease tumor cell proliferation, and induce apoptosis in SHH medulloblastomas in vitro and in vivo. Foretinib penetrated the blood-brain barrier and was effective in both the primary and metastatic tumor compartments. In established mouse xenograft or transgenic models of metastatic SHH medulloblastoma, foretinib administration reduced the growth of the primary tumor, decreased the incidence of metastases, and increased host survival. Taken together, our results provide a strong rationale to clinically evaluate foretinib as an effective therapy for patients with SHH-driven medulloblastoma. ©2014 American Association for Cancer Research.

The intraportal injection model: A practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer

International Nuclear Information System (INIS)

Thalheimer, Andreas; Waaga-Gasser, Ana M; Otto, Christoph; Bueter, Marco; Illert, Bertram; Gattenlohner, Stefan; Gasser, Martin; Meyer, Detlef; Fein, Martin; Germer, Christoph T

2009-01-01

The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. We injected immunoincompetent nude mice intraportally with different numbers (1 × 10 5 , 1 × 10 6 and 5 × 10 6 cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow. Only the injection of 1 × 10 6 cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 × 10 6 cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases. The present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD

Hepatic tuberculosis mimicking metastasis in a case of carcinoma sigmoid colon

Directory of Open Access Journals (Sweden)

Musharraf Husain

2015-01-01

Full Text Available Tuberculosis (TB presenting as isolated liver mass without clinical evidence of TB is difficult to diagnose preoperatively and is usually mimicked by primary or metastatic carcinoma of the liver. Hepatic TB associated with carcinoma colon is a rare association which has very rarely been reported in the literature. This case illustrates the diagnostic difficulties of hepatic TB and the need to consider it in the differential diagnosis of hepatic nodular lesions in carcinoma colon patients. Here, we report a case of 48-year-old female who presented in the casualty with features of acute intestinal obstruction. Preoperatively a mass was seen at the hepatic flexure along with three lesions in the liver presumed to be metastatic in origin. However, histopathology of the mass revealed adenocarcinoma colon and the liver lesion proved to be hepatic TB. We wish to highlight that on encountering a hepatic lesion in a carcinoma colon patient the possibility of hepatic TB should also be kept in mind apart from the obvious possibility of metastasis especially in an endemic country like India.

Photo-nano immunotherapy for metastatic cancers (Conference Presentation)

Science.gov (United States)

Zhou, Feifan

2016-03-01

We constructed a multifunction nano system SWNT-GC and investigated the synergize photothermal and immunological effects. Here, we improve the SWNT-GC nano system and design a new synergistic nano-particle, both have the photothermal effects and immunological effects. We investigate the therapeutic effects and detect the immune response with metastatic mouse tumor models. We also study the therapeutic mechanism after treatment in vitro and in vivo. With the enhancement of nano-materials on photothermal effects, laser treatment could destroy primary tumor and protect normal tissue with low dose laser irradiation. With the immunological effects of nano-materials, the treatment could trigger specific antitumor immune response, to eliminate the metastasis tumor. It is providing a promising treatment modality for the metastatic cancers.

CT of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Nakamura, H; Tanaka, T; Sai, H; Kawamoto, S; Morimoto, K [Osaka Univ. (Japan). Faculty of Medicine

1982-06-01

CT was investigated in 125 cases of hepatocelluar carcinoma and 47 cases of metastatic hepatic neoplasm. The entire contour of each tumor was traced and the average CT value in the tumor was estimated. As a result, the CT value for hepatocellular carcinoma tended to be higher on plain CT and also after contrast enhancement. The CT findings seen frequently were as follows: capsule in 76 cases (60.8%) and septum in 67 cases (53.6%); tumor thrombus in portal vein in 39 cases (31.2%) and that in inferior vena cava in 3 cases (2.4%); localized enlargement of hepatic bile duct in 24 cases (19.2%). These findings were rarely seen in the cases of metastatic hepatic neoplasm. As a relatively outstanding feature of hepatic metastases, a double contour, like concentric circles or contour lines, with a relatively large inner circle or contour line, was found in 21 cases (44.7%). By paying attention to the change of CT value on contrast enhancement and the characteristic image of each case, hepatocellular carcinoma could be differentiated from metastatic hepatic neoplasm with high probability.

MRI of metastatic adenocarcinomas to the brain. Differential diagnosis of colorectal and pulmonary cancer

International Nuclear Information System (INIS)

Fukusumi, Akio; Nakagawa, Hiroyuki; Takayama, Katsutoshi

1998-01-01

To clarify the characteristic features of MR imagings of metastatic adenocarcinomas to the brain and search for differential points between the lesions from colorectal cancer and those of lung cancer, we evaluated retrospectively intraparenchymal metastatic lesions of 13 colorectal origins and 13 pulmonary origins on MR imagings, compared with resected specimens. Metastatic lesions from colorectal cancer showed marked hypointense solid components on T2WI, which correspond to the dense tumor cells and coagulated necrosis pathologically. Metastatic lesions from lung cancers showed mixed intensity and various components on T2WI, which correspond to various histological components, such as solid tumor cell's nests, hemorrhage, necrosis and cystic fluid collection. Pathological specimens suggested that the low signal intensity on T2WI of MRI derived from concentration of tumor cells and coagulated necrosis including macrophages and lymphocytes. This study may contribute to make the differential diagnosis of metastatic adenocarcinomas to the brain from colorectal and pulmonary cancers. (author)

Mutational status of synchronous and metachronous tumor samples in patients with metastatic non-small-cell lung cancer

International Nuclear Information System (INIS)

Quéré, Gilles; Descourt, Renaud; Robinet, Gilles; Autret, Sandrine; Raguenes, Odile; Fercot, Brigitte; Alemany, Pierre; Uguen, Arnaud; Férec, Claude; Quintin-Roué, Isabelle; Le Gac, Gérald

2016-01-01

Despite reported discordance between the mutational status of primary lung cancers and their metastases, metastatic sites are rarely biopsied and targeted therapy is guided by genetic biomarkers detected in the primary tumor. This situation is mostly explained by the apparent stability of EGFR-activating mutations. Given the dramatic increase in the range of candidate drugs and high rates of drug resistance, rebiopsy or liquid biopsy may become widespread. The purpose of this study was to test genetic biomarkers used in clinical practice (EGFR, ALK) and candidate biomarkers identified by the French National Cancer Institute (KRAS, BRAF, PIK3CA, HER2) in patients with metastatic non-small-cell lung cancer for whom two tumor samples were available. A retrospective study identified 88 tumor samples collected synchronously or metachronously, from the same or two different sites, in 44 patients. Mutation analysis used SNaPshot (EGFR, KRAS, BRAF missense mutations), pyrosequencing (EGFR and PIK3CA missense mutations), sizing assays (EGFR and HER2 indels) and IHC and/or FISH (ALK rearrangements). About half the patients (52 %) harbored at least one mutation. Five patients had an activating mutation of EGFR in both the primary tumor and the metastasis. The T790M resistance mutation was detected in metastases in 3 patients with acquired resistance to EGFR tyrosine kinase inhibitors. FISH showed discordance in ALK status between a small biopsy sample and the surgical specimen. KRAS mutations were observed in 36 % of samples, six patients (14 %) having discordant genotypes; all discordances concerned sampling from different sites. Two patients (5 %) showed PI3KCA mutations. One metastasis harbored both PI3KCA and KRAS mutations, while the synchronously sampled primary tumor was mutation free. No mutations were detected in BRAF and HER2. This study highlighted noteworthy intra-individual discordance in KRAS mutational status, whereas EGFR status was stable. Intratumoral

Evaluation of factors affecting tumor response and survival in patients with primary and metastatic liver cancer treated with microspheres.

Science.gov (United States)

Demirelli, Serkan; Erkilic, Metin; Oner, Ali Ozan; Budak, Evrim Surer; Gunduz, Seyda; Ozgur, Ozhan; Bozcuk, Hakan; Sindel, Hakki Timur; Boz, Adil

2015-04-01

Radioembolization with the yttrium-90 (Y-90) microspheres is being used increasingly more often in the treatment of patients with primary or metastatic liver cancer. Although technetium-99m macroaggregated albumin (Tc-99m MAA) scintigraphy performed following diagnostic angiography has an important role in predicting the effectiveness of treatment and in dose estimation, the number of studies using quantitative assessment of Tc-99m MAA scintigraphy is limited in this field. In the present study, the aim was to assess whether a tumor dose is required to obtain objective tumor response and to check whether this threshold value is predictive in terms of tumor response, survival, and liver toxicity by using Tc-99m MAA single-photon emission computed tomography (SPECT) images. Overall, 54 patients (20 women and 34 men; median age: 60 years) who underwent Y-90 Resin (SIR-Spheres) and Glass (TheraSphere) microsphere treatment with a diagnosis of unresectable liver cancer between August 2010 and April 2013 were included in the study. The mean doses to normal liver and tumor were estimated for each patient using Tc-99m MAA SPECT images and the medical internal radiation dosimetry method. The responses were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) and European Organisation for Research and Treatment of Cancer (EORTC) criteria. Kaplan-Meier survival curves and univariate Cox regression analysis were used in survival analysis. The relationship between treatment response and other parameters included was assessed using logistic regression analysis. The variables with a P value less than 0.01 in univariate analysis were assessed with multivariate analysis. Fifty-four Y-90 microsphere treatments (eight by using a Y-90 glass microsphere and 46 by using a Y-90 resin microsphere) were performed. In the multivariate analysis, the only parameter related to response was tumor dose (P<0.01). With a tumor dose of 280 Gy or higher, objective tumor

Differential Expression of Matrix Metalloproteinase-2 Expression in Disseminated Tumor Cells and Micrometastasis in Bone Marrow of Patients with Nonmetastatic and Metastatic Prostate Cancer: Theoretical Considerations and Clinical Implications—An Immunocytochemical Study

Directory of Open Access Journals (Sweden)

Nigel P. Murray

2012-01-01

Full Text Available Matrix metalloproteinase-2 (MMP-2 is important in the dissemination and invasion of tumor cells and activates angiogenesis. We present an immunocytochemical study of MMP-2 expression in circulating prostate cells (CPCs, disseminated tumor cells (DTCs, and micrometastasis (mM in bone marrow of men with prostate cancer. Methods and Patients. Tumor cells were identified with anti-PSA immunocytochemistry. Positive samples underwent processing with anti-MMP-2, its expression was compared with Gleason score, concordance of expression, and metastatic and nonmetastatic disease. Results. 215 men participated, CPCs were detected in 62.7%, DTCs in 62.2%, and mM in 71.4% in nonmetastatic cancer; in metastatic cancer all had CPCs, DTCs, and mM detected. All CPCs and DTCs expressed MMP-2; in mM MMP-2 expression was positively associated with increasing Gleason score. MMP-2 expression in CPCs and DTCs showed concordance. In low grade tumors, mM and surrounding stromal cells were MMP-2 negative, with variable expression in high grade tumors; in metastatic disease, both mM and stromal cells were MMP-2 positive. Conclusions. CPCs and DTCs are different from mM, with inhibition of MMP-2 expression in mM of low grade tumors. With disease progression, MMP-2 expression increases in both mM and surrounding stromal cells, with implications for the use of bisphosphonates or MMP-2 inhibitors.

Tendencia de la incidencia de los tumores hepáticos en la infancia Incidence trends of hepatic tumors in childhood

Directory of Open Access Journals (Sweden)

Juan Manuel Mejía-Aranguré

2002-04-01

áticos en niños menores de 15 años, de 1982 a 1991, y de 1996 a 1999.Objective. To evaluate the incidence trends of hepatic tumors among children living in Mexico City. Material and Methods. A cross-sectional hospital survey was conducted to yield two databases. The first database contains the registry of all the cases of hepatic tumors occurring during the period 1982-1991, in public hospitals of Mexico City. The second database contains all hepatic tumor cases found between 1996 and 1999 in Hospital de Pediatría del Centro Médico Nacional "Siglo XXI" and in Hospital General del Centro Médico La Raza, both hospitals pertaining to Instituto Mexicano del Seguro Social (Mexican Institute of Social Security. The average annual incidence rates (AAIR were calculated for each type of hepatic tumor. The rates were standardized with the direct method, using as standard the world population under 15 years of age. The trends were evaluated with the annual incidence rates and the average rate of change assuming a Poisson distribution. Results. The AAIR for hepatoblastoma during the period 1982-1991 was three times higher for men than for women, with a value of 0.6 x10(6. The group of 1-4 years of age was the most affected. For hepatocarcinomas the AAIR was two-fold for women (0.14 as compared to men. Between 1996-1999 the AAIR for hepatoblastoma was 5.11 in women and 1.85 in men. The age group with the highest rate was women under one year of age. The AAIR for hepatocarcinoma was 0.64 for males and 1.23 for females. The most affected age group was males aged 10 to 14 years. No significant upward or downward trend was found in the incidence of hepatoblastomas. A non-significant change rate of 10% was found for hepatocarcinoma. Conclusions. No significant trends were observed in the incidence of hepatic tumors in children of Mexico City aged under 15 years, during the periods 1982-1991 and 1996-1999.

Intraarterial Chemotherapy or Chemoembolization for Locally Advanced and/or Recurrent Hepatic Tumors: Evaluation of the Feeding Artery with an Interventional CT System

International Nuclear Information System (INIS)

Hirai, Toshinori; Korogi, Yukunori; Ono, Ken; Maruoka, Kousei; Harada, Kazunori; Aridomi, Satoshi; Takahashi, Mutsumasa

2001-01-01

Purpose: To evaluate the utility of an interventional CT system for intraarterial chemotherapy or chemoembolization for locally advanced and/or recurrent hepatic tumors.Methods: Thirty-eight patients with locally advanced or recurrent hepatic tumors underwent 73 intraarterial contrast-enhanced CT (IA-CECT) examinations immediately before chemotherapy or chemoembolization. The degree of tumor vascularity on angiography and enhancement on IA-CECT was classified into three grades: no, mild, or marked vascularity. The IA-CECT grades were compared with the angiographic grades.Results: Twenty-nine (69%) of 42 examinations that were interpreted as having no or mild vascularity on angiography were classified as marked enhancement on IA-CECT. Based on IA-CECT findings, the position of the catheter was changed in 14 (19%) of 73 CT examinations. The reasons for the reposition were as follows: weak or no enhancement of the tumor (n = 11) or strong enhancement of the gallbladder wall (n = 3). The treatment strategy was changed in three patients (8%). No major complications relating to the interventional procedures were observed.Conclusions: IA-CECT is a reliable method when evaluating the perfusion of the tumor and adjacent normal tissues. The interventional CT system is useful for performing safe and effective intraarterial chemotherapy or chemoembolization in patients with locally advanced and/or recurrent hepatic tumors

Location of Primary Tumor and Benefit From Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer

Science.gov (United States)

Moretto, Roberto; Cremolini, Chiara; Rossini, Daniele; Pietrantonio, Filippo; Battaglin, Francesca; Mennitto, Alessia; Bergamo, Francesca; Loupakis, Fotios; Marmorino, Federica; Berenato, Rosa; Marsico, Valentina Angela; Caporale, Marta; Antoniotti, Carlotta; Masi, Gianluca; Salvatore, Lisa; Borelli, Beatrice; Fontanini, Gabriella; Lonardi, Sara; De Braud, Filippo

2016-01-01

Introduction. Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. Patients and Methods. Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated. Results. Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p = .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p < .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97; 95% confidence interval: 2.09–7.53; p < .0001). Conclusion. Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti-EGFRs. Implications for Practice: Right- and left-sided colorectal tumors have peculiar epidemiological and clinicopathological characteristics, distinct gene expression profiles and genetic alterations, and different prognoses. This study assessed the potential predictive impact of primary tumor site with regard to anti-epidermal growth factor receptor (EGFR) monoclonal antibody treatment in patients with RAS and BRAF wild-type metastatic colorectal cancer. The results demonstrated the lack of activity of anti-EGFRs in RAS and BRAF wild-type, right-sided tumors, thus suggesting a potential role for primary tumor location in driving treatment choices

Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration.

Science.gov (United States)

Piao, Chunmei; Cai, Lun; Qiu, Shulan; Jia, Lixin; Song, Wenchao; Du, Jie

2015-04-24

Complement 5a (C5a), a potent immune mediator generated by complement activation, promotes tumor growth; however, its role in tumor metastasis remains unclear. We demonstrate that C5a contributes to tumor metastases by modulating tumor inflammation in hepatic metastases of colon cancer. Colon cancer cell lines generate C5a under serum-free conditions, and C5a levels increase over time in a murine syngeneic colon cancer hepatic metastasis model. Furthermore, in the absence of C5a receptor or upon pharmacological inhibition of C5a production with an anti-C5 monoclonal antibody, tumor metastasis is severely impaired. A lack of C5a receptor in colon cancer metastatic foci reduces the infiltration of macrophages, neutrophils, and dendritic cells, and the role for C5a receptor on these cells were further verified by bone marrow transplantation experiments. Moreover, C5a signaling increases the expression of the chemokine monocyte chemoattractant protein-1 and the anti-inflammatory molecules arginase-1, interleukin 10, and transforming growth factor β, but is inversely correlated with the expression of pro-inflammatory molecules, which suggests a mechanism for the role of C5a in the inflammatory microenvironment required for tumor metastasis. Our results indicate a new and potentially promising therapeutic application of complement C5a inhibitor for the treatment of malignant tumors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas.

Science.gov (United States)

Lüke, Julia; Vukoja, Vlatka; Brandenbusch, Tim; Nassar, Khaled; Rohrbach, Jens Martin; Grisanti, Salvatore; Lüke, Matthias; Tura, Aysegül

2016-06-03

Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis. The expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression). CD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non-metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident. These data may indicate that CD147 regulates MMP-2 expression in uveal melanoma cells.

Profil Gangguan Kognitif pada Tumor Intrakranial Primer dan Metastasis

Directory of Open Access Journals (Sweden)

Kartika Maharani

2015-12-01

Full Text Available Gangguan kognitif sering menyertai pasien tumor intrakranial dan menjadi penyebab utama disabilitas. Perbedaan patofisiologi tumor intrakranial primer (TIP dan metastasis (TM menyebabkan perbedaan gambaran klinis dan derajat  gangguan kognitif. Tujuan penelitian ini untuk mengetahui prevalensi dan profil gangguan kognitif pasien TIP dan TM. Disain penelitian potong-lintang retrospektif menggunakan data sekunder dari Poliklinik Saraf RSCM pada bulan Januari 2011-Desember 2013. Subjek berusia 18-65 tahun yang didiagnosis TIP dan TM berdasarkan anamnesis, pemeriksaan fisik, CT scan atau MRI kepala, dan atau histopatologi. Terdapat 121 subjek, 79 TIP dan 27 TM; usia rerata TIP 43,7 tahun dan TM 50,9 tahun. Pada kelompok TM mayoritas (40,7% memiliki lesi di kedua hemisfer sedangkan TIP hanya di satu hemisfer. Lokasi tumor pada TM lebih dari 1 lobus (51,9%. Gangguan kognitif lebih banyak pada TM (81,5% dibandingkan TIK (52,5% dengan domain tersering gangguan visuospasial. Subjek TM mengalami gangguan kognitif lebih berat dibandingkan TIP (rerata MMSE 20,96 dan 22,61. Gangguan kognitif lebih banyak pada kelompok TM dibandingkan TIP dengan gangguan kognitif lebih berat karena mayoritas lesi tumor mengenai lebih dari 1 lobus. Kata kunci: gangguan kognitif, tumor intrakranial, neuro-onkologi.   Cognitve Impairment in Primary and Metastatic Brain Tumors Abstract Brain tumor patients are often accompanied by a wide range of cognitive impairment as a major cause of disablility. The different pathophysiology of primary and metastatic brain tumor influences patients’ clinical signs and symptoms, and also the severity of cognitive impairment. To determine the prevalence and profile of cognitive impairment in patients with primary and metastatic brain tumors, this cross-sectional study was done on subjects of 18 to 65 years old with the diagnosis of primary and metastatic brain tumors based on anamnesis, physical examination, imaging modalities, and

Novel anti-metastatic action of cidofovir mediated by inhibition of E6/E7, CXCR4 and Rho/ROCK signaling in HPV tumor cells.

Directory of Open Access Journals (Sweden)

Abdessamad Amine

Full Text Available Cervical cancer is frequently associated with HPV infection. The expression of E6 and E7 HPV oncoproteins is a key factor in its carcinogenicity and might also influence its virulence, including metastatic conversion. The cellular mechanisms involved in metastatic spread remain elusive, but pro-adhesive receptors and their ligands, such as SDF-1alpha and CXCR4 are implicated. In the present study, we assessed the possible relationship between SDF-1alpha/CXCR4 signaling, E6/E7 status and the metastatic process. We found that SDF-1alpha stimulated the invasion of E6/E7-positive cancer cell lines (HeLa and TC-1 in Matrigel though CXCR4 and subsequent Rho/ROCK activation. In pulmonary metastatic foci generated by TC-1 cells IV injection a high proportion of cells expressed membrane-associated CXCR4. In both cases models (in vitro and in vivo cell adhesion and invasion was abrogated by CXCR4 immunological blockade supporting a contribution of SDF-1alpha/CXCR4 to the metastatic process. E6 and E7 silencing using stable knock-down and the approved anti-viral agent, Cidofovir decreased CXCR4 gene expression as well as both, constitutive and SDF-1alpha-induced cell invasion. In addition, Cidofovir inhibited lung metastasis (both adhesion and invasion supporting contribution of E6 and E7 oncoproteins to the metastatic process. Finally, potential signals activated downstream SDF-1alpha/CXCR4 and involved in lung homing of E6/E7-expressing tumor cells were investigated. The contribution of the Rho/ROCK pathway was suggested by the inhibitory effect triggered by Cidofovir and further confirmed using Y-27632 (a small molecule ROCK inhibitor. These data suggest a novel and highly translatable therapeutic approach to cervix cancer, by inhibition of adhesion and invasion of circulating HPV-positive tumor cells, using Cidofovir and/or ROCK inhibition.

Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer.

Science.gov (United States)

Piao, Chunmei; Zhang, Wen-Mei; Li, Tao-Tao; Zhang, Cong-Cong; Qiu, Shulan; Liu, Yan; Liu, Sa; Jin, Ming; Jia, Li-Xin; Song, Wen-Chao; Du, Jie

2018-05-15

Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells. C5aR was expressed on TAMs, which exhibited an M2-like functional profile in colon cancer liver metastatic lesions. Furthermore, C5a mediated macrophage polarization and this process relied substantially on activation of the nuclear factor-kappa B (NF-κB) pathway. Finally, analysis of human colon carcinoma indicated that C5aR expression is negatively associated with tumor differentiation grade. Our results demonstrate that C5aR has a central role in regulating the M2 phenotype of TAMs, which in turn, contributes to hepatic metastasis of colon cancer through NF-κB signaling. C5a is a potential novel marker for cancer prognosis and drugs targeting complement system activation, specifically the C5aR pathway, may offer new therapeutic opportunities for colon cancer management. Copyright © 2018 Elsevier Inc. All rights reserved.

131I-MIBG scintigraphy in carcinoid tumor with liver metastases (case report)

International Nuclear Information System (INIS)

Eftekhari, M.; Olamaei, R.; Fard, A.; Beiki, D.; Saghari, M.

2003-01-01

A 65 year old male presented with abdominal pain (R.U.Q) and constipation, associated with weight loss and anorexia since 40 days prior to admission. Serum biochemical tests were normal. Colonoscopy showed hemorrhagic polyploid lesion in the cecum Barium enema revealed filling defect in the cecum. Sonography revealed a target-shaped lesion(3cm X 2.5 cm)in upper segment of the right hepatic lobe. CT scan confirmed the same finding as a hypodense lesion. Following segmental resection of the cecum, pathology indicated the presence of the carcinoid tumor. For the better evaluation, 131 I-MIBG scintigraphy was carried out, demonstrating tracer avid metastatic lesions in the right and left hepatic lobes. A review of the series reported in the literature, shows that approximately 50-60% of carcinoids are able to concentrate radiolabeled MIBG. MIBG uptake apparently correlated with the urinary excretion of 5-HIAA, although this is not a universal finding. The most frequently occurring midgut carcinoids probably concentrate the radiolabeled MIBG more readily than those in the hind gut and fore gut. Primary and residual tumors are sometimes visualized , but the most striking imaging is that of carcinoids metastases in the peritoneum and liver(provided that SPECT images with 123 I-MIBG or alternatively 131 I-MIBG delayed scans are performed). Lymph node involvement, bone deposits and ovarian metastases have been reported as well. When radioiodinated MIBG and somatostatin scintigraphy results are compared, somatostatin scintigraphy shows a better sensitivity (>80%) in detecting both primary and metastatic lesions. These radiopharmaceuticals play complementary roles in that each give unique information concerning possible treatment either with octreotide or 131 I-MIBG, or both. MIBG imaging can not generally relied upon either to detect a carcinoid, or to rule out the disease.When a tumor is strongly suspected of being carcinoid however, the test can be worthwhile for the

Sputum cytology of a metastatic postradiation sarcoma

International Nuclear Information System (INIS)

Tanaka, Toshio; Murakami, Itsuko; Awai, Seiji; Ogura, Yasuko; Morishita, Yumiko

1981-01-01

A female patient who died of apparent postradiation sarcoma in the inguinal region after irradiating a metastatic squamous cell carcinoma of the same site was reported. For approximately 20 months, the patient had received a total of 6,600 and 9,600 Roentgen to the right para-aortic and inguinal areas, respectively. About 10 years later, she developed a sarcoma, namely a malignant fibrous histiocytoma. Sputum cytology demonstrated numerous giant cells with bizarre nuclei; subsequent chest films also presented apparent metastatic tumor shadows. The cellular characteristics and also rather low incidence of detection of nonepithelial malignant tumor by sputum cytology were briefly discussed, and ways of enhancing cytodiagnostic accuracy were proposed. (author)

Nodular Hepatic Tuberculosis Masquerading as a Seminoma Liver Metastasis.

Science.gov (United States)

Harbi, Houssem; Chaabouni, Amine; Kallel, Rim; Toumi, Nozha; Fendri, Sami; Krichene, Jihene; Boujelbene, Salah; Mzali, Rafik

2018-04-01

Isolated macro-nodular liver tuberculosis is a very rare condition. It may mimic primitive or secondary tumors of the liver. This could delay or mislead the therapeutic management. An immunocompetent 48-year-old man with a history of non-metastatic seminoma was treated with right orchidectomy followed by 20 Gy radiotherapy. The discovery, 8 months later, of a 2 cm nodule of the hepatic dome evoked a liver metastasis. Percutaneous biopsy was not feasible. Wedge resection was performed whereas medical treatment would have sufficed, as pathologic examination of the resected specimen showed a macro-nodular hepatic tuberculosis. The patient received anti-tuberculosis drugs for 9 months. The diagnosis of isolated macro-nodular liver tuberculosis is frequently misleading, particularly in immunocompetent and paucisymptomatic patients. Thus percutaneous biopsy is mandatory for diagnosis and also prior to any major surgeries. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry

Directory of Open Access Journals (Sweden)

Jiyoon Jung

2017-03-01

Full Text Available Background Colorectal cancer (CRC is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2 has emerged as a useful technique to complement polymerase chain reaction (PCR analyses. Methods In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results Based on IHC, 7/61 primary tumors (11.4% showed deficient MMR systems, while 13/61 secondary tumors (21.3% showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61. These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

CT analysis of intratumoral gas formation after hepatic tumor embolization

International Nuclear Information System (INIS)

Kim, Hyun Sook; Ahn, In Oak; Kim, Hyung Jin; Lee, Goo; Chung, Sung Hoon

1994-01-01

To evaluate the prevalence and the patterns of sterile gas shown at computed tomography(CT) after transarterial embolization(TAE) for primary hepatic tumor. Among 102 patients who performed TAE for hepatoma, thirty-four in whom follow-up CT was underwent constituted the basis of our study. At CT, we evaluated the patterns and locations of intratumoral gas. We also reviewed the clinical data to exclude an infectious origin of intratumoral gas. Of 34 patients, intratumoral gas was detected in 11 patients(32%), in all of whom Gelfoam was used as an embolic material. The initial tumor size measured at pre-TAE CT was larger in patients with intratumoral gas than in patients without it(p < 0.005). No specific patterns or locations of intratumoral gas were noted on CT scans. No patients had clinical signs and symptoms that suggested infection. Intratumoral gas formation without clinical evidence of infection is not an infrequent finding after TAE for hepatoma, especially when Gelfoam is used and when the tumor is larger in size. This finding may be a part of postinfarction syndrome and should not be misinterpreted as an postprocedural abscess formation

Inferior phrenic artery embolization in the treatment of hepatic neoplasms

International Nuclear Information System (INIS)

Duprat, G.; Charnsangavej, C.; Wallace, S.; Carrasco, C.H.

1988-01-01

Twenty-nine inferior phrenic artery embolizations were performed in 20 patients with primary or metastatic hepatic neoplasms. All patients had interruption of their hepatic arteries by previous infusion of chemotherapy, hepatic arterial embolization or surgical ligation. In one patient, bilateral pleural effusions developed following embolization of the inferior phrenic artery. No other severe complications occurred. Inferior phrenic artery embolization is a safe procedure and permits the continuation of transcatheter treatment of hepatic neoplasms. (orig.)

Inferior phrenic artery embolization in the treatment of hepatic neoplasms

Energy Technology Data Exchange (ETDEWEB)

Duprat, G.; Charnsangavej, C.; Wallace, S.; Carrasco, C.H.

Twenty-nine inferior phrenic artery embolizations were performed in 20 patients with primary or metastatic hepatic neoplasms. All patients had interruption of their hepatic arteries by previous infusion of chemotherapy, hepatic arterial embolization or surgical ligation. In one patient, bilateral pleural effusions developed following embolization of the inferior phrenic artery. No other severe complications occurred. Inferior phrenic artery embolization is a safe procedure and permits the continuation of transcatheter treatment of hepatic neoplasms.

Comparison of AMI-25 enhanced MRI and helical dynamic CT in the detection of hepatic lesions

International Nuclear Information System (INIS)

Saitou, Kazuhiro; Matsuda, Hiromichi; Fukushima, Hiroaki; Kanzaki, Hiroshi; Hirose, Takashi; Karizaki, Dai; Abe, Kimihiko; Amino, Saburou

1994-01-01

We performed AMI-25 enhanced MRI and helical dynamic CT in 12 cases of hepatic lesions. Nine of these were hepatocellular carcinomas. Two cases were metastatic liver tumors (the primary lesion was gastric in one and the other was gallbladder cancer). One case was suspected to be adenomatous hyperplasia. Thirty-two lesions were detected in T2-weighted SE images before AMI-25 administration, while 46 lesions were detected in AMI-25 enhanced MRI images. In particular, AMI-25 enhanced MRI was superior to plain MRI in lesions less than 10 mm in size. A total of 48 lesions were detected in helical dynamic CT. Although AMI-25 enhanced MRI almost equaled helical dynamic CT in the detection of liver tumors, helical dynamic CT was slightly superior to AMI-25 enhanced MRI in the detection of subphrenic lesions. It was possible to know the hemodynamics in each hepatic lesion by helical dynamic CT. AMI-25 enhanced MRI was useful to know the inclusion of reticuloendothelial system, and that yielded different diagnoses in adenomatous hyperplasia and well differentiated hepatocellular carcinoma. Helical dynamic CT was useful for qualitative diagnosis. Both AMI-25 enhanced MRI and helical dynamic CT contributed to the detection of liver tumor and qualitative diagnosis. (author)

Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

DEFF Research Database (Denmark)

Nielsen, D L; Nørgaard, H; Weber Vestermark, Lene

2012-01-01

The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease.......The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease....

The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

Directory of Open Access Journals (Sweden)

Angela M Poff

Full Text Available INTRODUCTION: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. METHODS: We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week. Tumor growth was monitored by in vivo bioluminescent imaging. RESULTS: KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. CONCLUSIONS: KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

Breast cancer metastatic to the kidney with renal vein involvement.

Science.gov (United States)

Nasu, Hatsuko; Miura, Katsutoshi; Baba, Megumi; Nagata, Masao; Yoshida, Masayuki; Ogura, Hiroyuki; Takehara, Yasuo; Sakahara, Harumi

2015-02-01

The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

The intensity of 18FDG uptake does not predict tumor growth in patients with metastatic differentiated thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Terroir, Marie; Dercle, Laurent; Lumbroso, Jean; Baudin, Eric; Berdelou, Amandine; Deandreis, Desiree; Schlumberger, Martin; Leboulleux, Sophie [Gustave Roussy and Universite Paris Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif (France); Borget, Isabelle [University Paris Sud, Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif (France); Bidault, Francois [Gustave Roussy, Department of Radiology, Villejuif (France); Ricard, Marcel [Gustave Roussy, Department of Physic, Villejuif (France); Deschamps, Frederic; Tselikas, Lambros [Department of Interventional Radiology, Villejuif (France); Hartl, Dana [Gustave Roussy, Department of Surgery, Villejuif (France)

2017-04-15

In patients with metastatic differentiated thyroid carcinoma (DTC), fluorodeoxyglucose (FDG) uptake as well as age, tumor size and radioactive iodine (RAI) uptake are prognostic factors for survival. High FDG uptake is a poor prognostic factor and lesions with high FDG uptake are often considered aggressive, but the predictive value of FDG uptake for morphological progression is unknown. The principal aim of this retrospective single center study was to determine whether the intensity of FDG uptake was correlated on a per lesion analysis with tumor growth rate (TGR) expressed as the percentage of increase in tumor size during 1 year (1-year TGR). Fifty five patients with DTC were included between July 2012 and May 2014 with the following criteria: (i) at least one distant metastasis measuring ≥ 1 cm in diameter on CT scan (ii) evaluation by FDG-positron emission tomography/computed tomography (PET/CT) performed at our center (iii) at least one CT or another FDG-PET/CT performed 3 to 12 months after the reference FDG-PET/CT in the absence of systemic or local treatment between the two imaging procedures. One hundred and fifty-six metastatic lesions located in lungs (63), neck lymph nodes (28), chest lymph nodes (42), bone (11), liver (2) and other sites (12) were studied. The median size was 16 mm, median SUVmax/lesion: 8.7; median metabolic tumor volume/lesion (Metab.TV/lesion): 3.7 cm{sup 3}. The median 1-year TGR was 40.68 %. SUVmax and Metab.TV/lesion were not correlated to their 1-year TGR (p = 0.38 and p = 0.74 respectively). Among single patients with multiple lesions, the lesions with the highest SUVmax/lesion or the highest Metab.TV/lesion did not disclose the higher 1-year TGR. The intensity of FDG uptake on a per lesion analysis is not correlated to its 1-year TGR and cannot be used as a surrogate marker of tumour progression. (orig.)

Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy

Czech Academy of Sciences Publication Activity Database

Aaltonen, K. E.; Novosadová, Vendula; Bendahl, P.-O.; Graffman, C.; Larsson, A.-M.; Ryden, L.

2017-01-01

Roč. 8, č. 28 (2017), s. 45544-45565 ISSN 1949-2553 Institutional support: RVO:86652036 Keywords : metastatic breast cancer * circulating tumor cells * gene expression Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 5.168, year: 2016

IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

Science.gov (United States)

Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

2016-10-27

Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8 + T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8 + T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with

Novel immunotherapy approaches for metastatic urothelial and renal cell carcinoma

Directory of Open Access Journals (Sweden)

Zhiying Shao

2016-10-01

Full Text Available The treatment of metastatic renal cell carcinoma (RCC and urothelial carcinoma (UC remains a major challenge. Past research has implicated the immune system in tumor surveillance of both malignancies, leading to the application of immunotherapy agents for both cancers. Among them, the most promising agents are the checkpoint blockade drugs, such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, programmed death receptor 1 (PD-1, and PD-1 ligand (PD-L1. In normal physiology, these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions, which is pivotal for maintaining self-tolerance. However, tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response, leading to disease progression and metastasis. Thus, there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC. To date, nivolumab (anti-PD-1 and atezolizumab (anti-PD-L1 have been approved for the treatment of metastatic RCC and UC, respectively. Despite these successes, challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach. In this report, we review existing data and research on immunotherapy in metastatic RCC and UC.

The effect of pre-vertebroplasty tumor ablation using laser-induced thermotherapy on biomechanical stability and cement fill in the metastatic spine.

Science.gov (United States)

Ahn, Henry; Mousavi, Payam; Chin, Lee; Roth, Sandra; Finkelstein, Joel; Vitken, Alex; Whyne, Cari

2007-08-01

A biomechanical study comparing simulated lytic vertebral metastases treated with laser-induced thermotherapy (LITT) and vertebroplasty versus vertebroplasty alone. To investigate the effect of tumor ablation using LITT prior to vertebroplasty on biomechanical stability and cement fill patterns in a standardized model of spinal metastatic disease. Vertebroplasty in the metastatic spine is aimed at reducing pain, but is associated with risk of cement extravasation in up to 10%. Six pairs of fresh-frozen cadaveric thoracolumbar spinal motion segments were tested in axial compression intact, with simulated metastases and following percutaneous vertebroplasty with or without LITT. Canal narrowing under load, pattern of cement fill, load to failure, and LITT temperature and pressure generation were collected. In all LITT specimens, cement filled the defect without extravasation. The canal extravasation rate was 33% in specimens treated without LITT. LITT and vertebroplasty yielded a trend toward improved posterior wall stability (P = 0.095) as compared to vertebroplasty alone. Moderate rises in temperature and minimal pressure generation was seen during LITT. In this model, elimination of tumor by LITT, facilitates cement fill, enhances biomechanical stability and reduces the risk of cement extravasation.

Hepatic Intra-arterial Delivery of a "Trojan-horses" Gene Therapy: A Pilot Study on Rabbit VX2 Hepatic Tumor Model.

Science.gov (United States)

Pellerin, Olivier; Amara, Ikram; Sapoval, Marc; Méachi, Tchao; Déan, Carole; Beaune, Philippe; de Waziers, Isabelle

2018-01-01

Gene-directed enzyme prodrug therapy (GDEPT) is a "Trojan-horses" suicide gene therapy that consists of tumor-targeted gene delivery (vectorized by mesenchymal stem cells MSCs) encoding an enzyme that converts a harmless prodrug into cytotoxic metabolites in situ. Then, cytotoxic metabolites passively diffuse in the neighboring tumor cells and kill them (bystander effect). The goal of our study was to assess the feasibility and efficacy of intra-arterial administration of MSCs transduced with an optimized gene (MSC-CYP2B6TM-RED) followed by intravenous administration of cyclophosphamide (CPA) into the VX2 rabbit liver tumor. Nine rabbits with a VX2 liver tumor were randomly assigned into three groups: Control group A (one rabbit) free of any treatment; Control group B (two rabbits) receiving intravenous injection of cyclophosphamide at day 3 and CPA at day 14; and Group C (six rabbits) receiving the GDEPT treatment, consisting of successive intra-arterial injection of transduced-MSCs at days 0 (n = 6) and 11 (n = 3), followed by injection of CPA at days 3 (n = 6) and 14 (n = 3). The tumor response was assessed by ultrasound scan every 7 days and histopathological analysis at sacrifice (D25). There was a significant difference in the tumor volume between control groups (A + B) and group C at D7: 38/19 cm 3 (p = 0.024); D11: 51/20 cm 3 (p = 0.024), and D25: 121/37 cm 3 (p = 0.048). Tumor necrosis was significantly greater and metastatic spread was lower for rabbits who received GDEPT (78% of total tumor surface) than for control animals (A + B) (22% of total tumor surface (p = 0.006). Intra-arterial delivery of transduced-MSCs is feasible and, after CPA injection, resulted in 78% tumor necrosis (p = 0.006) and less metastasis in a VX2 liver tumor model.

Dynamic-thresholding level set: a novel computer-aided volumetry method for liver tumors in hepatic CT images

Science.gov (United States)

Cai, Wenli; Yoshida, Hiroyuki; Harris, Gordon J.

2007-03-01

Measurement of the volume of focal liver tumors, called liver tumor volumetry, is indispensable for assessing the growth of tumors and for monitoring the response of tumors to oncology treatments. Traditional edge models, such as the maximum gradient and zero-crossing methods, often fail to detect the accurate boundary of a fuzzy object such as a liver tumor. As a result, the computerized volumetry based on these edge models tends to differ from manual segmentation results performed by physicians. In this study, we developed a novel computerized volumetry method for fuzzy objects, called dynamic-thresholding level set (DT level set). An optimal threshold value computed from a histogram tends to shift, relative to the theoretical threshold value obtained from a normal distribution model, toward a smaller region in the histogram. We thus designed a mobile shell structure, called a propagating shell, which is a thick region encompassing the level set front. The optimal threshold calculated from the histogram of the shell drives the level set front toward the boundary of a liver tumor. When the volume ratio between the object and the background in the shell approaches one, the optimal threshold value best fits the theoretical threshold value and the shell stops propagating. Application of the DT level set to 26 hepatic CT cases with 63 biopsy-confirmed hepatocellular carcinomas (HCCs) and metastases showed that the computer measured volumes were highly correlated with those of tumors measured manually by physicians. Our preliminary results showed that DT level set was effective and accurate in estimating the volumes of liver tumors detected in hepatic CT images.

Basic and clinical studies of dynamic sequential computed tomography during arterial portography in the diagnosis of hepatic cancers

International Nuclear Information System (INIS)

Matsui, Osamu

1986-01-01

The author has developed dynamic sequential computed tomography with table incrementation during arterial portography (DSCTI-AP) for the precise diagnosis of liver cancers. 1. Basic Studies on DSCTI-AP; 1) The phantom experiment simulating DSCTI-AP revealed that it is possible to resolve a cylindrical object 5 mm in diameter with more than 50 Hounsfield Unit (HU) difference in the attenuation value compared to the surrounding area by third generation CT scanner. 2) All macroscopically visible nodules of hepatocellular carcinoma (HCC) chemically induced in rat liver and VX2 tumor transplanted via the portal vein in rabbit liver were visualized as portal perfusion defects on portal microangiograms and nodular low density areas in CT during portography. 2. Analysis of the clinical usefulness of DSCTI-AP; 1) The smallest nodules of HCC and metastatic liver cancer detected by DSCTI-AP were 5 mm in diameter. 2) DSCTI-AP was superior to radionuclide liver scanning, ultrasound (US), computed tomography (CT), selective celiac arteriography (SCA) and infusion hepatic angiography (IHA) in the detection of small HCC. But IHA was superior to DSCTI-AP in visualizing extremely hypervascular HCC nodules, and all of the small HCCs were demonstrated by the combination of DSCTI-AP and IHA. 3) DSCTI-AP was superior to the all other imaging modalities including CT following intraarterial injection of iodized oil (Lipiodol CT) in detecting metastatic liver cancers especially less than 1 cm in diameter. 4) Lipiodol CT was superior to DSCTI-AP in visualizing small hypervascular HCC nodules. 5) DSCTI-AP was the most sensitive method in diagnosing peripheral intrahepatic portal tumor thrombus. 6) DSCTI-AP had the advantage in visualizing the location of hepatic tumors and their relation to major vessels objectively. (J.P.N.)

A Case Report of Unilateral Severe Visual Loss Along with Bilateral Optic Disc Cupping Secondary to Metastatic Brain Tumor

Directory of Open Access Journals (Sweden)

M Mahdavi

2006-07-01

Full Text Available Purpose: To report a case of unilateral severe visual loss and bilateral optic disc cupping secondary to brain metastasis of bronchogenic carcinoma Patient and findings: A 48 year-old woman presented with severe visual loss of left eye without redness or pain or any systemic findings .Clinical findings included decreased visual acuity of left eye to 4 m CF and (+3 positive Marcus-Gunn reflex .There was asymmetric optic disc cupping associated with visual field defect in left eye The neurologic investigations showed a secondary metastatic tumor in the brain from bronchogenic carcinoma. Conclusion: Before making a diagnosis of normal -tension glaucoma in asymmetric optic disc cupping and normal intraocular pressure, ophthalmologists should rule out neurologic defects and brain tumors.

Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC

Directory of Open Access Journals (Sweden)

Rossi L

2013-11-01

Full Text Available Luigi Rossi, Foteini Vakiarou, Federica Zoratto, Loredana Bianchi, Anselmo Papa, Enrico Basso, Monica Verrico, Giuseppe Lo Russo, Salvatore Evangelista, Guilia Rinaldi, Francesca Perrone-Congedi, Gian Paolo Spinelli, Valeria Stati, Davide Caruso, Alessandra Prete, Silverio TomaoDepartment of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Rome, Italy; Oncology Unit, ICOT, Latina, ItalyAbstract: Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features.Keywords: metastatic colorectal cancer, patient clinical features, tumor biology, multidisciplinary approach

Prediction of treatment response and metastatic disease in soft tissue sarcoma

Science.gov (United States)

Farhidzadeh, Hamidreza; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Raghavan, Meera.; Gatenby, Robert A.

2014-03-01

Soft tissue sarcomas (STS) are a heterogenous group of malignant tumors comprised of more than 50 histologic subtypes. Based on spatial variations of the tumor, predictions of the development of necrosis in response to therapy as well as eventual progression to metastatic disease are made. Optimization of treatment, as well as management of therapy-related side effects, may be improved using progression information earlier in the course of therapy. Multimodality pre- and post-gadolinium enhanced magnetic resonance images (MRI) were taken before and after treatment for 30 patients. Regional variations in the tumor bed were measured quantitatively. The voxel values from the tumor region were used as features and a fuzzy clustering algorithm was used to segment the tumor into three spatial regions. The regions were given labels of high, intermediate and low based on the average signal intensity of pixels from the post-contrast T1 modality. These spatially distinct regions were viewed as essential meta-features to predict the response of the tumor to therapy based on necrosis (dead tissue in tumor bed) and metastatic disease (spread of tumor to sites other than primary). The best feature was the difference in the number of pixels in the highest intensity regions of tumors before and after treatment. This enabled prediction of patients with metastatic disease and lack of positive treatment response (i.e. less necrosis). The best accuracy, 73.33%, was achieved by a Support Vector Machine in a leave-one-out cross validation on 30 cases predicting necrosis treatment and metastasis.

Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors.

Science.gov (United States)

Roussos, Evanthia T; Wang, Yarong; Wyckoff, Jeffrey B; Sellers, Rani S; Wang, Weigang; Li, Jiufeng; Pollard, Jeffrey W; Gertler, Frank B; Condeelis, John S

2010-01-01

The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tumor microenvironment for metastasis (TMEM), an anatomical structure that is predictive for risk of breast cancer metastasis. Previously we have shown that forced expression of Mena adenocarcinoma cells enhances invasion and metastasis in xenograft mice. Whether Mena is required for tumor progression is still unknown. Here we report the effects of Mena deficiency on tumor progression, metastasis and on normal mammary gland development. To investigate the role of Mena in tumor progression and metastasis, Mena deficient mice were intercrossed with mice carrying a transgene expressing the polyoma middle T oncoprotein, driven by the mouse mammary tumor virus. The progeny were investigated for the effects of Mena deficiency on tumor progression via staging of primary mammary tumors and by evaluation of morbidity. Stages of metastatic progression were investigated using an in vivo invasion assay, intravital multiphoton microscopy, circulating tumor cell burden, and lung metastases. Mammary gland development was studied in whole mount mammary glands of wild type and Mena deficient mice. Mena deficiency decreased morbidity and metastatic dissemination. Loss of Mena increased mammary tumor latency but had no affect on mammary tumor burden or histologic progression to carcinoma. Elimination of Mena also significantly decreased epidermal growth factor (EGF) induced in vivo invasion, in vivo motility, intravasation and metastasis. Non-tumor bearing mice deficient for Mena also showed defects in mammary gland terminal end bud formation and branching. Deficiency of Mena decreases metastasis by slowing tumor progression and reducing tumor cell invasion and intravasation. Mena

Quantitative Method of Measuring Metastatic Activity

Science.gov (United States)

Morrison, Dennis R. (Inventor)

1999-01-01

The metastatic potential of tumors can be evaluated by the quantitative detection of urokinase and DNA. The cell sample selected for examination is analyzed for the presence of high levels of urokinase and abnormal DNA using analytical flow cytometry and digital image analysis. Other factors such as membrane associated uroldnase, increased DNA synthesis rates and certain receptors can be used in the method for detection of potentially invasive tumors.

Are Breast Tumor Stem Cells Responsible for Metastasis and Angiogenesis?

National Research Council Canada - National Science Library

Pan, Quintin

2005-01-01

.... The current dogma of metastasis is that most primary tumor cells have low metastatic potential, but rare cells, less than one in ten million, within large primary tumors acquire metastatic capacity...

Enhanced metastatic potential of murine fibrosarcomas treated in vitro with ultraviolet radiation

International Nuclear Information System (INIS)

Fisher, M.S.; Cifone, M.A.

1981-01-01

The purpose of this study was to determine whether repeated treatment of tumor cells in vitro with mutagenic doses of ultraviolet (UV) radiation could influence the metastatic behavior of these cells in vivo. Three cloned lines of UV-2237, a fibrosarcoma induced in a C3H- mouse by chronic irradiation with UV, and SF-19, a spontaneous C3H- fibrosarcoma, were grown in culture. These cell lines varied from low to high metastatic potential as determined by in vivo tests. The cultures were exposed to UV radiation from an FS40 sunlamp at a dose that killed 40% of the cells. These UV radiation exposures were repeated at 3- to 5-day intervals for a total of 5 treatments. The mutation frequency was analyzed by monitoring the appearance of ouabain-resistant colonies following UV irradiation. With all four tumor lines, the frequency of conversion to ouabain resistance was increased more than 10-fold. Tumor cells given 5 UV radiation treatments and control cultures carried in parallel without exposure to UV radiation were tested for metastatic potential in an in vivo lung colony assay. Cell lines treated in vitro with UV radiation produced more experimental metastases than the counterpart unirradiated cultures. We conclude that, in all four tumor lines, exposure of tumorigenic cells to mutagenic doses of UV radiation can alter their biological behavior and that this may contribute to the progression of tumors from low to high metastatic capability

Cediranib for Metastatic Alveolar Soft Part Sarcoma

Science.gov (United States)

Kummar, Shivaani; Allen, Deborah; Monks, Anne; Polley, Eric C.; Hose, Curtis D.; Ivy, S. Percy; Turkbey, Ismail B.; Lawrence, Scott; Kinders, Robert J.; Choyke, Peter; Simon, Richard; Steinberg, Seth M.; Doroshow, James H.; Helman, Lee

2013-01-01

Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib. PMID:23630200

Evaluation of reserved hepatic function in patients with hepatobiliary tumor by 99mTc-GSA. Effect of hyperbilirubinemia and usefulness of regional reserved hepatic functional imaging

International Nuclear Information System (INIS)

Jin Wu; Ishikawa, Nobuyoshi; Takeda, Tohoru; Sato, Motohiro; Todoroki, Takeshi; Itai, Yuji; Fukunaga, Kiyoshi; Okumura, Toshiyuki; Hatakeyama, Rokurou.

1996-01-01

The evaluation of the reserved hepatic function was performed by 99m Tc-galactosyl serum albumin ( 99m Tc-GSA) in 70 patients with hepatobiliary tumor. The dynamic study was performed to evaluate global reserved hepatic function following the intravenous bolus injection of 99m Tc-GSA, and the hepatic single photon emission computed tomography (SPECT) was obtained to assess the regional reserved hepatic function. The functional hepatic index (LHL 15 ) was derived from liver time-activity data, and it was compared with serum total-bilirubin level, serum albumin level and plasma disappearance rate of indocyanine green (ICG 15 ). In the patients with hepatocellular carcinoma, LHL 15 value agreed well with ICG 15 value, serum total-bilirubin level, and serum albumin level. Moderate or severe hepatic dysfunction was observed at 65.4% of these patients. In the patients with cholangiocellular carcinoma, a discrepancy of LHL 15 value and ICG 15 value was observed. Increment of the ICG 15 value was correlated with that of the serum total-bilirubin level, whereas the correlation was not observed between the LHL 15 value and the serum total-bilirubin level. These results indicate that 99m Tc-GSA scintigraphy can evaluate the reserved hepatic function without the embellishment of jaundice. This method is useful for assessing the global and regional reserved hepatic function. (author)