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Sample records for stages i-iii crc

  1. Stage I/II endometrial carcinomas: preoperative radiotherapy: results

    International Nuclear Information System (INIS)

    Maingon, P.; Belichard, C.; Horiot, J.C.; Barillot, I.; Fraisse, J.; Collin, F.

    1996-01-01

    The AIM of this retrospective study is to analyse the indications and the results of treatment of endometrial carcinomas by preoperative radiotherapy. MATERIAL: From 1976 to 1995, 183 patients FIGO stage I or II were treated by preoperative radiotherapy consisting in 95 cases of external radiotherapy (XRT) and brachytherapy (BT) followed by surgery (S) and, in 88 cases of BT alone before surgery, XRT was indicated in cases of grade 2 or 3 and/or cervical involvement. METHODS: XRT was delivered with a 4-fields technique to 40 Gy in 20 fractions with a medial shielding at 30 Gy. BT was done with low dose rate Cs137 and Fletcher-Suit-Delclos applicators with two intra-uterine tubes and vaginal ovoieds. Complications were scored using the French-Italian syllabus. RESULTS: Five-year actuarial survival rates per stage are: Ia=91%, Ib=83%, II=71%, and per grade: G1=80%, G2=79%, G3=90%. Failures were pelvic in 5/183 (2.7%), vaginal in 4 cases (2%) and nodal in 2 cases (1%). Twelve patients developed metastases (6.5%). Complications were analysed during the radiotherapy, after the surgery and with unlimited follow-up. After BT/S, 12 grade 1, 1 grade 2 and 1 grade 3 complications were observed. In the group of patients treated by RT/BT/S, 22 grade 1, 11 grade 2, 4 grade 3 occurred. There is no statistical correlation between complications and parameters of treatment (XRT, hwt, HWT, reference dose to the bladder and rectum, dose rate of brachytherapy). SUMMARY: Preoperative irradiation is an effective and safe treatment of high risk stage I/II endometrial carcinomas. Results seem independent of the pathology grade

  2. Factors affecting number of lymph nodes harvested and the impact of examining a minimum of 12 lymph nodes in stage I-III colorectal cancer patients: a retrospective single institution cohort study of 1167 consecutive patients.

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    Tsai, Hsiang-Lin; Huang, Ching-Wen; Yeh, Yung-Sung; Ma, Cheng-Jen; Chen, Chao-Wen; Lu, Chien-Yu; Huang, Ming-Yii; Yang, I-Ping; Wang, Jaw-Yuan

    2016-04-14

    To identify factors affecting the harvest of lymph nodes (LNs) and to investigate the association between examining a minimum of 12 LNs and clinical outcomes in stage I-III colorectal cancer (CRC) patients. The clinicopathologic features and the number of examined LNs for 1167 stage I-III CRC patients were analyzed to identify factors affecting the number of LNs harvested and the correlations between clinical outcomes and high harvests (≧12 LNs) and low harvests (cancer and that tumor size (P = 0.015) was the only independent factor in rectal cancer. Patients with low harvests had poorer overall survival with stage II and stage III CRC (stage II: P number of examined LNs (≧12) is associated with a survival benefit. Removal of at least 12 LNs will determine the lymph node status reliably.

  3. The relation between lymph node status and survival in Stage I-III colon cancer

    DEFF Research Database (Denmark)

    Lykke, J.; Roikjær, Ole; Jess, P.

    2013-01-01

    Aim: This study involved a large nationwide Danish cohort to evaluate the hypothesis that a high lymph node harvest has a positive effect on survival in curative resected Stage I-III colon cancer and a low lymph node ratio has a positive effect on survival in Stage III colon cancer. Method......: Analysis of overall survival was conducted using a nationwide Danish cohort of patients treated with curative resection of Stage I-III colon cancer. All 8901 patients in Denmark diagnosed with adenocarcinoma of the colon and treated with curative resection in the period 2003-2008 were identified from...... independent prognostic factors in multivariate analysis. Conclusion: High lymph node count was associated with improved overall survival in colon cancer. Lymph node ratio was superior to N-stage in differentiating overall survival in Stage III colon cancer. Stage migration was observed....

  4. Pegylated Liposomal Doxorubicin as Adjuvant Therapy for Stage I-III Operable Breast Cancer.

    Science.gov (United States)

    Lu, Yin-Che; Ou-Yang, F U; Hsieh, Chia-Ming; Chang, King-Jen; Chen, Dar-Ren; Tu, Chi-Wen; Wang, Hwei-Chung; Hou, Ming-Feng

    2016-01-01

    Conventional anthracyclines play an essential role for the treatment of breast cancer and have potent cytotoxic activity, but are associated with severe toxicity. In metastatic breast cancer, pegylated liposomal doxorubicin (PLD) is a formulation with efficacy similar to conventional doxorubicin but with reduced toxicity. This multicenter study evaluated the efficacy and safety of PLD-based adjuvant chemotherapy for women with stage I-III operable breast cancer. One hundred and eighty women with stage I-III breast cancer who received PLD-based adjuvant chemotherapy at six different Institutions in Taiwan from February 2002 to March 2008 were included and followed-up until April 2015. Treatment efficacy was determined by disease-free survival (DFS) rate and safety was evaluated by adverse events. The 5- and 10-year DFS rates were 76.3 and 72.6%, respectively. Univariate analysis revealed that tumor size >5 cm (p=0.045; hazard ratio=3.31) and stage III (hazard ratio=3.54; p=0.019) were each associated with shorter DFS. Only stage III (hazard ratio=5.60; p=0.018) retained statistical significance with regard to DFS in the multivariate analysis. Grade 3/4 hematological toxicity was neutropenia (n=13; 7.2%). The women receiving PLD had low-grade 3 or 4 nausea/vomiting, mucositis, and alopecia. Grade 3 hand-foot syndrome occurred in three patients (1.7%). PLD could be considered an effective and safe alternative to conventional anthracyclines in the treatment of stage I-III operable breast cancer. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

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    Swords, Douglas S; Mulvihill, Sean J; Skarda, David E; Finlayson, Samuel R G; Stoddard, Gregory J; Ott, Mark J; Firpo, Matthew A; Scaife, Courtney L

    2017-07-11

    To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

  6. Stage I-II squamous cell carcinoma of the oral cavity treated by iridium-192

    International Nuclear Information System (INIS)

    Piedbois, P.; Mazeron, J.J.; Haddad, E.; Coste, A.; Martin, M.; Levy, C.; Raynal, M.; Pavlovitch, J.M.; Peynegre, R.; Perquin, B.; Bourgeois, J.P. le

    1991-01-01

    This is a retrospective analysis of 233 evaluable patients with stage I-II squamous cell carcinoma of the oral cavity treated by definitive brachytherapy. Minimum follow-up is 3 years. Treatment of the neck was chosen by a multidisciplinary team, according to age, medical status and availability for follow-up. One hundred and ten patients (47 percent) underwent elective neck dissection (END), 28 (25 percent) had positive nodes and received neck irradiation post-operatively. One hundred and twenty-three patients (53 percent) were regularly followed up only, with therapeutic neck dissection (TND) reserved for cases of node relapses. In the END group, there were 19 neck relapses (17 percent): 12/60 (20 percent) in patients with mobile tongue carcinoma and 7/50 (14 percent) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 13-21 (62 percent) cases. Ten-year survival is 37 percent for the END-group and 31 percent for the TND group. Tumour stage and infiltration into underlying tissues increased the probability of neck relapse and death. Furthermore, a multivariate analysis showed that patients treated in the TND group had a higher probability of death than patients treated in the END group (p<0.04). (author). 30 refs.; 2 figs.; 7 tabs

  7. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

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    Carmona, Ruben; Gulaya, Sachin; Murphy, James D. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Rose, Brent S. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Wu, John; Noticewala, Sonal [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T. [Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Department of Family and Preventive Medicine, Biostatistics and Bioinformatics, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  8. Breast-conserving therapy (BCT) in stage I-II synchronous bilateral breast cancer (SBBC)

    International Nuclear Information System (INIS)

    Gollamudi, Smitha V.; Gelman, Rebecca S.; Peiro, Gloria; Schneider, Lindsey; Connolly, James L.; Schnitt, Stuart; Silver, Barbara; Harris, Jay R.

    1995-01-01

    PURPOSE: To determine whether patients with early-stage SBBC can be safely and effectively treated with bilateral BCT. MATERIALS and METHODS: We retrospectively reviewed records of 26 patients with clinical Stage I-II SBBC treated between 1968-1989 with bilateral BCT. SBBC was defined as tumors diagnosed no more than one month apart, with both sides demonstrating invasive cancer. Maximum (max) clinical stage was based on the more advanced breast tumor. Median age at diagnosis was 56 years (range, 32-85 years); menopausal status was 6 pre-, 16 post-, 3 peri-, and 1 unknown at diagnosis. Median follow-up for surviving pts is 95 months (range, 68-157). Outcome was compared to 1325 pts with unilateral Stage I or II breast cancer, within the same age range, treated during the same time period. There were no significant differences in median age, median total dose, tumor size, estrogen receptor (ER) status, pathologic nodal status, and use of systemic therapy between the study population and the comparison group. Local recurrence (LR) was evaluated as true recurrence (TR, i.e., in the original tumor bed), marginal miss (MM, at the edge of the boost field), or elsewhere (E). Median total dose to the primary was 6100 cGy (range, 5000-7000). Pathology was available for review in 19 cases. Cytology (nuclear and cytoplasmic features) was similar in (7(19)) evaluable cases, and architecture (growth pattern, ie, papillary, solid) was similar in (5(19)) cases. The presence of either cytologic or architectural similarity was noted in(9(19)) cases. 7 of 19 pts who had axillary lymph node evaluation on at least one side had pathological confirmation of lymph node metastasis. Stage was the same in both breasts in 13 cases (10 Stage I, 3 Stage II); ER status data was complete in 11 pts, and the same in both primaries in 9 cases. Cosmetic results and complications after BCT were scored. Statistical significance was evaluated by use of the Fisher exact test. RESULTS: The 5-yr actuarial

  9. Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

    Science.gov (United States)

    2017-04-12

    Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell

  10. Individualized nomogram improves diagnostic accuracy of stage I-II gallbladder cancer in chronic cholecystitis patients with gallbladder wall thickening.

    Science.gov (United States)

    Zhou, Di; Wang, Jian-Dong; Yang, Yong; Yu, Wen-Long; Zhang, Yong-Jie; Quan, Zhi-Wei

    2016-04-01

    Early diagnosis of gallbladder cancer (GBC) can remarkably improve the prognosis of patients. This study aimed to develop a nomogram for individualized diagnosis of stage I-II GBC in chronic cholecystitis patients with gallbladder wall thickening. The nomogram was developed using logistic regression analyses based on a retrospective cohort consisting of 89 consecutive patients with stage I-II GBC and 1240 patients with gallbladder wall thickening treated at one biliary surgery center in Shanghai between January 2009 and December 2011. The accuracy of the nomogram was validated by discrimination, calibration and a prospective cohort treated at another center between January 2012 and December 2014 (n=928). Factors included in the nomogram were advanced age, hazardous alcohol consumption, long-standing diagnosed gallstones, atrophic gallbladder, gallbladder wall calcification, intraluminal polypoid lesion, higher wall thickness ratio and mucosal line disruption. The nomogram had concordance indices of 0.889 and 0.856 for the two cohorts, respectively. Internal and external calibration curves fitted well. The area under the receiver-operating characteristic curves of the nomogram was higher than that of multidetector row computed tomography in diagnosis of stage I-II GBC (Pcholecystitis patients with gallbladder wall thickening, especially for those the imaging features alone do not allow to confirm the diagnosis.

  11. Exercise in Targeting Metabolic Dysregulation in Stage I-III Breast or Prostate Cancer Survivors

    Science.gov (United States)

    2017-09-12

    Cancer Survivor; No Evidence of Disease; Obesity; Overweight; Prostate Carcinoma; Sedentary Lifestyle; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  12. Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer

    Science.gov (United States)

    2018-04-17

    Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage I Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma; Uterine Corpus Sarcoma

  13. Treatment outcome, body image, and sexual functioning after orchiectomy and radiotherapy for Stage I-II testicular seminoma

    International Nuclear Information System (INIS)

    Incrocci, Luca; Hop, Wim C.J.; Wijnmaalen, Arendjan; Slob, A. Koos

    2002-01-01

    Purpose: Orchiectomy followed by infradiaphragmatic irradiation is the standard treatment for Stage I-II testicular seminoma in The Netherlands. Because body image and sexual functioning can be affected by treatment, a retrospective study was carried out to assess treatment outcome, body image, and changes in sexuality after orchiectomy and radiotherapy. Methods and Materials: The medical charts of 166 patients with Stage I-II testicular seminoma were reviewed. A questionnaire on body image and current sexual functioning regarding the frequency and quality of erections, sexual activity, significance of sex, and changes in sexuality was sent to 157 patients (at a mean of 51 months after treatment). Results: Seventy-eight percent (n=123, mean age 42 years) completed the questionnaire. During irradiation, almost half of patients experienced nausea and 19% nausea and vomiting. Only 3 patients had disease relapse. After treatment, about 20% reported less interest and pleasure in sex and less sexual activity. Interest in sex, erectile difficulties, and satisfaction with sexual life did not differ from age-matched healthy controls. At the time of the survey, 17% of patients had erectile difficulties, a figure that was significantly higher than before treatment, but which correlated also with age. Twenty percent expressed concerns about fertility, and 52% found their body had changed after treatment. Cancer treatment had negatively influenced sexual life in 32% of the patients. Conclusions: Orchiectomy with radiotherapy is an effective and well-tolerated treatment for Stage I-II testicular seminoma. Treatment-induced changes in body image and concerns about fertility were detected, but the sexual problems encountered did not seem to differ from those of healthy controls, although baseline data are lacking

  14. Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older

    International Nuclear Information System (INIS)

    Furuta, Masaya; Hayakawa, Kazushige; Katano, Susumu

    1996-01-01

    Between 1976 and 1992, 32 patients aged 75 and older with stage I-II non-small cell lung cancer (NSCLC) were given definitive radiation therapy. These patients did not undergo surgery because of old age, poor cardiac/pulmonary condition, or refusal to give consent. The mean age was 79 years, and 11 patients were over 80 years old. The histologic type was squamous cell carcinoma in 25 patients and adenocarcinoma in 7. The clinical T and N stage was T1N0 in 4 patients, T2N0 in 9, and T2N0 in 19. The total dose of radiation therapy given to each patient exceeded 60 Gy using 10-MV X-rays. The treatment was completed in all 32 patients without treatment-related complications. The 2- and 5-year overall actuarial survival rates were 40% and 16%, respectively. Eleven intercurrent deaths occurred, including 7 patients who died of heart disease. The 2- and 5-year cause-specific survival rates were 57% and 36%, respectively. None of the patients developed severe pneumonitis requiring hospitalization. All but three patients received radiation therapy on an inpatient basis. The mean duration of the hospital stay for initial treatment was 56 days, and mean ratio to total survival period (mean 739 days) was 8%. Although many elderly patients have concurrent medical complications such as heart disease and chronic pulmonary disease, the present study showed that elderly patients with clinical stage I-II NSCLC can expert a realistic probability of long-term survival with definitive radiation therapy. (author)

  15. Stage I-II carcinoma of the anterior two-thirds of the tongue treated with different modalities

    International Nuclear Information System (INIS)

    Akine, Yasuyuki; Tokita, Nobuhiko; Ogino, Takashi; Tsukiyama, Iwao; Egawa, Sunao; Saikawa, Masahisa; Ohyama, Waichiro; Yoshizumi, Takashi; Ebihara, Satoshi

    1991-01-01

    Treatment results of 244 patients with stage I-II cancer of the mobile tongue were analyzed according to the modalities employed (implantation, surgery, cryosurgery and intraoral irradiation). Overall local control rates at 3 years were 90+-3 percent for implant, 89+-7 percent for cryosurgery, and 84+-9 percent for surgery. Local control rates in stage II patients treated with intraoral electron irradiation, however, were only 50+-13 percent. Five-year survival rates were 72+-3 percent with no significant differences observed in patients with either stage I or stage II regardless of treatment modality. Sixty percent (29/48) of the patients with local recurrences were salvaged by the 2nd treatment. Since the local control and survival achieved by these modalities were similar, with the exception of patients with stage II treated by intraoral electron irradiation, authors recommend inter-stitial implantation with iridium, intraoral electron irradiation or surgery for patients with T 1 tumors, and iridium implantation or surgery for patients with T 2 tumors. For those with superficial lesions measuring 5 mm or less in thickness, cryosurgery is being offered as an alternative. The patient can choose the treatment modality taking into account his/her age, sex and profession. (author). 13 refs.; 1 fig.; 4 tabs

  16. Radiotherapy in stage I-III follicular non-Hodgkin lymphoma. Retrospective analysis of a series of 50 patients

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    Fakhrian, K.; Klemm, S.; Bayer, C.; Riedl, W.; Molls, M.; Geinitz, H. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Keller, U. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). III. Medical Dept.

    2012-06-15

    The goal of this work was to analyze the response rate and outcome of patients with stage I-III follicular lymphoma (FL) treated with radiotherapy (RT) alone. The records of 50 consecutive patients with stage I-III FL treated with RT alone at our department from 1988-2009 were analyzed. The median age was 60 years (range 32-80 years) with a median follow-up duration of 8 years (range 4-11 years). Clinical staging was performed according to the Ann Arbor system. Stage I: 30 patients (60%), stage II: 15 patients (30%), stage III: 5 patients (10%). Thirty-two patients (64%) presented with nodal disease, 14 patients (28%) presented with disease in extranodal sites, and 4 patients (8%) had nodal and extranodal involvement. The RT field encompassed only the involved Ann Arbor nodal regions (involved-field RT) in 26 patients (52%), mantle and whole abdominopelvic fields in 6 patients (12%), mantle field in 10 patients (20%), whole abdominopelvic fields in 5 patients (10%), and a so-called mini-mantle in 3 patients (6%). The total RT dose ranged from 26-56 Gy (median 40 Gy) in daily fractions of 1.2-2.5 Gy. Complete remission (CR) and partial remission (PR) were observed in 39 (76%) and 9 (20%) patients, respectively. Only 2 of 8 patients (25%) with tumor bulk > 5 cm reached CR, whereas 37 of 42 patients (88%) with a maximum lymphoma diameter < 5 cm achieved CR (p = 0.0001). The median overall survival (OS) and median event-free survival (EFS) were 18 years (CI 95% 10-26 years) and 7 years (6-8 years), respectively. The 2-, 5-, and 10-year OS were 96 {+-} 3%, 90 {+-} 5%, and 70 {+-} 9%, respectively. The 2-, 5-, and 10-year EFS were 90 {+-} 5%, 70 {+-} 7%, and 38 {+-} 9%, respectively. Fifteen patients developed a recurrence outside the radiation field (30%) and 4 patients developed an in-field recurrence (8%). All in-field recurrences were observed in regions without clinical (macroscopic) involvement, which were irradiated with a dose of {<=} 26 Gy. Pretreatment maximum

  17. The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

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    Pruijt Hans FM

    2011-05-01

    Full Text Available Abstract Background The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC. In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0 will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs and/or micrometastases (MMs at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0micro+ patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0micro+ and evaluate the benefits from adjuvant chemotherapy in pN0micro+ CC patients. Methods/design EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an ex vivo sentinel lymph node mapping procedure (SLNM following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0micro+ are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS. Discussion The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 micro+ CC patients by reducing disease recurrence by adjuvant chemotherapy. Trial Registration ClinicalTrials.gov: NCT01097265

  18. Recurrences and toxicity after adjuvant vaginal brachytherapy in Stage I-II endometrial cancer: A monoinstitutional experience.

    Science.gov (United States)

    Perrucci, Elisabetta; Lancellotta, Valentina; Bini, Vittorio; Zucchetti, Claudio; Mariucci, Cristina; Montesi, Giampaolo; Saccia, Stefano; Palumbo, Isabella; Aristei, Cynthia

    2016-01-01

    To evaluate the incidences of vaginal recurrence and toxicity after vaginal brachytherapy in Stage I-II endometrial cancer. Between 2003 and 2012, 150 high-intermediate-risk Stage I and 7 Stage II patients, median age 64 years, underwent surgery, with or without lymphadenectomy, and 3D brachytherapy: 7 Gy, at 5 mm depth from applicator surface, for 3-week fractions. The effects of age, grading, number of excised lymph nodes and pathologic stage on loco-regional relapse (LRR), metastases, and tumor-related death were investigated. Vaginal toxicity was evaluated during followup visits. At 83 months of median followup, 144 patients were disease free, 2 in relapse, 7 deceased from disease, and 4 from other causes. One vaginal (0.6%), five nodal (3.2%), three pelvic over the vaginal cuff (1.9%), and one distant recurrences were seen (0.6%). The 5-year probability of LRR-free, distant metastasis-free and cause-specific survivals for all patients were 93.6% (95% confidence interval [CI]: 88.1-96.7), 97.8% (95% CI: 93.2-99.3), and 96.5% (95% CI: 93.5-99.5) and for Stage I 95.7% (95% CI: 92.2-9.1), 99.3% (95% CI: 98.0-100), and 97.7% (95% CI: 95.2-100), respectively. At multivariate analysis, Stage II disease and more than 12 lymph nodes sampled were associated with LRR (hazard ratio [HR]: 3.88; 95% CI: 1.390-10.878; p = 0.010 and HR: 6.952; 95% CI: 1.591-30.385; p = 0.010) and Stage II with metastasis and tumor-related death (HR: 23.057; 95% CI: 2.296-231.485; p = 0.008 and HR: 4.324; 95% CI: 1.223-15.290; p = 0.023). Vaginal acute and chronic toxicity was 16% and 55.4%, respectively, all only Grades 1-2. For high-to-intermediate-risk Stage I endometrial cancer, 3D vaginal brachytherapy achieved good local control and low toxicity. In Stage II, patients brachytherapy could be administered after complete surgical staging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  19. Macrophage markers in serum and tumor have prognostic impact in American Joint Committee on Cancer stage I/II melanoma

    DEFF Research Database (Denmark)

    Jensen, T.O.; Schmidt, H.; Moller, H.J.

    2009-01-01

    melanomas from 190 patients were available for immunohistochemical analyzes of CD163(+) and CD68(+) macrophage infiltration. They were estimated semiquantitatively in three different tumor compartments: tumor nests, tumor stroma, and at the invasive front of the tumor. RESULTS: Serum sCD163 treated......, HR = 1.4; 95% CI, 1.1 to 1.8; P = .003). Melanomas with dense CD163(+) macrophage infiltration in tumor stroma and CD68(+) macrophage infiltration at the invasive front were associated with poor overall survival (CD163, HR = 2.7; 95% CI, 0.8 to 9.3; P = .11; and CD68, HR = 2.8; 95% CI, 1.2 to 6.8; P...... = .02) independent (borderline for CD163) of thickness and ulceration. CONCLUSION: Both serum levels of sCD163 and the presence of CD68(+) macrophage infiltration at the tumor invasive front are independent predictors of survival in AJCC stage I/II melanoma. CD163(+) cell infiltration in tumor stroma...

  20. The expression of chemokine receptors CXCR3 and CXCR4 in predicting postoperative tumour progression in stages I-II colon cancer: a retrospective study.

    Science.gov (United States)

    Du, Changzheng; Yao, Yunfeng; Xue, Weicheng; Zhu, Wei-Guo; Peng, Yifan; Gu, Jin

    2014-01-01

    The prognostic significance of chemokine receptors in stage I/II colon cancer is unclear. We assessed the prognostic value of chemokine receptor CXCR3 and CXCR4 in stage I/II colon cancer. 145 patients with stage I/II colon cancer who underwent curative surgery alone from 2000 to 2007 were investigated. Chemokine receptor expression was assessed by immunohistochemistry. The associations between CXCR3, CXCR4 and clinicopathological variables were analysed using the χ2 test, and the relationships between chemokine receptors and a 5-year disease-free survival were analysed by univariate and multivariate analyses. The high-expression rates of CXCR3 and CXCR4 were 17.9% (26/145) and 38.6% (56/145), respectively. There were no significant associations between the expressions of CXCR3, CXCR4 and clinicopathological factors including gender, age, tumour location, histological differentiation, pathological stage, lymphovascular invasion and pretreatment serum carcinoembryonic antigen (CEA). The 5-year disease-free survival was not significantly different between low-expression groups and high-expression groups of CXCR3 and CXCR4. Multivariate analysis revealed that serum CEA and a number of retrieved lymph nodes, rather than chemokine receptors, were independent prognosticators. CXCR3 and CXCR4 are not independent prognosticators for stage I/II colon cancer after curative surgery.

  1. Quality of life after Sentinal Lymph Node Biopsy or Axillary Node Dissection in Stage I/II Breast Patients: A Prospective Longitunal Study

    NARCIS (Netherlands)

    Kootstra, Jan; Hoekstra-Weebers, Josette E.H.M.; Rietman, Johan Swanik; de Vries, Jaap; Baas, Peter; Geertzen, Jan H.B.; Hoekstra, Harald J.

    2008-01-01

    Background: Breast cancer patients’ quality of life (QoL) after surgery has been reported to improve significantly over time. Little is known about QoL recovery after sentinel lymph node biopsy (SLNB) in comparison to axillary lymph node dissection (ALND). Methods: 175 of 195 stage I/II breast

  2. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse

    DEFF Research Database (Denmark)

    Raemaekers, John M M; André, Marc P E; Federico, Massimo

    2014-01-01

    PURPOSE: Combined-modality treatment is standard treatment for patients with clinical stage I/II Hodgkin lymphoma (HL). We hypothesized that an early positron emission tomography (PET) scan could be used to adapt treatment. Therefore, we started the randomized EORTC/LYSA/FIL Intergroup H10 trial ...

  3. Association of time-to-surgery with outcomes in clinical stage I-II pancreatic adenocarcinoma treated with upfront surgery.

    Science.gov (United States)

    Swords, Douglas S; Zhang, Chong; Presson, Angela P; Firpo, Matthew A; Mulvihill, Sean J; Scaife, Courtney L

    2017-12-13

    Time-to-surgery from cancer diagnosis has increased in the United States. We aimed to determine the association between time-to-surgery and oncologic outcomes in patients with resectable pancreatic ductal adenocarcinoma undergoing upfront surgery. The 2004-2012 National Cancer Database was reviewed for patients undergoing curative-intent surgery without neoadjuvant therapy for clinical stage I-II pancreatic ductal adenocarcinoma. A multivariable Cox model with restricted cubic splines was used to define time-to-surgery as short (1-14 days), medium (15-42), and long (43-120). Overall survival was examined using Cox shared frailty models. Secondary outcomes were examined using mixed-effects logistic regression models. Of 16,763 patients, time-to-surgery was short in 34.4%, medium in 51.6%, and long in 14.0%. More short time-to-surgery patients were young, privately insured, healthy, and treated at low-volume hospitals. Adjusted hazards of mortality were lower for medium (hazard ratio 0.94, 95% confidence interval, .90, 0.97) and long time-to-surgery (hazard ratio 0.91, 95% confidence interval, 0.86, 0.96) than short. There were no differences in adjusted odds of node positivity, clinical to pathologic upstaging, being unresectable or stage IV at exploration, and positive margins. Medium time-to-surgery patients had higher adjusted odds (odds ratio 1.11, 95% confidence interval, 1.03, 1.20) of receiving an adequate lymphadenectomy than short. Ninety-day mortality was lower in medium (odds ratio 0.75, 95% confidence interval, 0.65, 0.85) and long time-to-surgery (odds ratio 0.72, 95% confidence interval, 0.60, 0.88) than short. In this observational analysis, short time-to-surgery was associated with slightly shorter OS and higher perioperative mortality. These results may suggest that delays for medical optimization and referral to high volume surgeons are safe. Published by Elsevier Inc.

  4. Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

    Science.gov (United States)

    2017-11-15

    Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

  5. Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation

    International Nuclear Information System (INIS)

    Fuller, Lillian M.; Krasin, Matthew J.; Velasquez, William S.; Allen, Pamela K.; McLaughlin, Peter; Rodriguez, M. Alma; Hagemeister, Fredrick B.; Swan, Forrest; Cabanillas, Fernando; Palmer, Judy L.; Cox, James D.

    1995-01-01

    Purpose: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). Methods and Materials: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or ≥ 40 Gy and (b) relapse patterns. Results: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of ≥ 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. Conclusion: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients

  6. A Prospective Study of Comparing Multi-Gene Biomarker Chip and Serum Carcinoembryonic Antigen in the Postoperative Surveillance for Patients with Stage I-III Colorectal Cancer.

    Science.gov (United States)

    Chang, Yu-Tang; Huang, Ming-Yii; Yeh, Yung-Sung; Huang, Ching-Wen; Tsai, Hsiang-Lin; Cheng, Tian-Lu; Wang, Jaw-Yuan

    2016-01-01

    Circulating biomarkers can predict clinical outcomes in colorectal cancer patients. The aim of the study was to evaluate the feasibility of our multigene biomarker chip for detecting circulating tumor cells for postoperative surveillance of stage I-III colorectal cancer patients. In total, 298 stage I-III colorectal cancer patients were analyzed after curative resection between June 2010 and October 2014. During each follow-up, a postoperative surveillance strategy, including ESMO Guidelines Working Group recommendations and the biochip, was used. After a 28.4-month median follow-up, 48 (16.1%) patients had postoperative relapse. Univariate analysis revealed that the postoperative relapse risk factors were rectal tumor, perineural invasion, elevated preoperative and postoperative serum carcinoembryonic antigen levels, and positive biochip results (all P carcinoembryonic antigen levels (odds ratio = 4.136, P = 0.008) and positive biochip results (odds ratio = 66.878, P carcinoembryonic antigen levels. Moreover, the median lead time between positive biochip result and postoperative relapse detection was significantly earlier than that between elevated postoperative serum carcinoembryonic antigen level and postoperative relapse detection (10.7 vs. 2.8 months, P carcinoembryonic antigen detection, our multigene chip aided more accurate and earlier prediction of postoperative relapse during stage I-III colorectal cancer patient surveillance. In clinical practice, this biochip may facilitate early postoperative relapse diagnosis in colorectal cancer patients.

  7. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    Science.gov (United States)

    2017-08-07

    Anxiety Disorder; Depression; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  8. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    Science.gov (United States)

    2017-06-14

    Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  9. The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer

    Science.gov (United States)

    2018-03-02

    Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

  10. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    Science.gov (United States)

    2017-06-29

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  11. Demographics and Outcomes of Stage I-II Merkel Cell Carcinoma Treated with Mohs Micrographic Surgery Compared with Wide Local Excision in the National Cancer Data Base.

    Science.gov (United States)

    Singh, Babu; Qureshi, Muhammad M; Truong, Minh Tam; Sahni, Debjani

    2018-02-03

    The optimal surgical approach (wide local excision (WLE) vs. Mohs micrographic surgery (MOHS)) for treating Merkel cell carcinoma (MCC) is yet to be determined. To compare survival outcomes in patients with early stage MCC treated with MOHS versus WLE. A retrospective review of all cases in the National Cancer Data Base (NCDB) of MCC of clinical Stage I-II MCC treated with WLE or MOHS was performed. 1,795 cases of Stage I-II MCC were identified who underwent WLE (N=1,685) or MOHS (N=110). There was no difference in residual tumor on surgical margins between the two treatment groups (p=0.588). On multivariate analysis, there was no difference in overall survival between the treatment modalities (adjusted HR 1.02; 95% CI 0.72-1.45, p=0.897). There was no difference in overall survival between the two groups on propensity score matched analysis. Disease specific survival was not reported as this data in not available in the NCDB. MOHS appears to be as effective as WLE in treating early stage MCC. Copyright © 2018. Published by Elsevier Inc.

  12. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    International Nuclear Information System (INIS)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  13. Monitoring CO2 injection with a buried geophone array: Stage 2C of CO2CRC Otway Project

    Science.gov (United States)

    Urosevic, M.; Gurevich, B.; Pevzner, R.; Tertyshnikov, K.; Shulakova, V.; Glubokovskikh, S.; Popik, D.; Kepic, A.; Robertson, M.; Freifeld, B. M.; Daley, T. M.; Singh, R.

    2015-12-01

    The Stage 2 of the CO2CRC project involves injection of a small quantity of CO2, 15 Kt, into the Paaratte formation, a saline aquifer located at a depth of around 1500 m in the Otway basin, Victoria, Australia. The project aims to investigate the limits of time lapse seismic methodologies in order to devise an optimal monitoring program. That includes time lapse signal and noise prediction, time lapse data acquisition design and finally data analysis. The strength of the time lapse (TL) seismic is governed by the magnitudes of both the time lapse signal and time lapse noise. They are in turn both dependent on numerous factors which need to be addressed through modelling studies and data acquisition technologies. Geological information is used to build a detailed 3D static model for the dynamic reservoir simulations and analysis of CO2 plume distribution for small quantities of CO2 injected into the deepest Paaratte member. Various lithological scenarios and variations in permeability distribution are tested until arriving at the "most likely" solution. The final model is used initially for 1D and subsequently for the full 3D time lapse modelling. These time lapse modelling results, combined with field tests and noise analysis, show clearly that small quantities of CO2 injected into a relatively thin (~20 m in thickness) saline aquifer would benefit from utilizing a permanent 3D seismic array to achieve desired repeatability, that is reduction in time lapse seismic noise. Buried receiver array was designed and deployed at the CO2CRC Otway during January and February. The array comprises 908 high-sensitivity geophones deployed at 4 m depth below the surface. Baseline 3D was acquired in March 2015. Some 3003 shots were acquired by a crew of 7 people over 9 days. Benchmark tests show a significant improvement in data quality compared to surface geophones. With this approach there are no cables or other seismic infrastructure on the surface. This significantly reduces

  14. Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Ruella, Marco [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia (United States); Filippi, Andrea Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Bruna, Riccardo [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Di Russo, Anna [Radiation Oncology, Istituto Nazionale Tumori, Milano (Italy); Magni, Michele [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Caracciolo, Daniele [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Passera, Roberto [Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Matteucci, Paola; Di Nicola, Massimo [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Corradini, Paolo [Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Parvis, Guido [Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino (Italy); Gini, Guido; Olivieri, Attilio [Division of Haematology, Ospedali Riuniti, Ancona (Italy); Ladetto, Marco [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Tarella, Corrado, E-mail: corrado.tarella@gmail.com [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Hemato-Oncology Division, European Institute of Oncology, Milano (Italy); Devizzi, Liliana [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy)

    2016-03-15

    Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m{sup 2}, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

  15. Lymphography and computed tomography of abdominal nodes in newly diagnosed patients with Hodgkin's disease in clinical stage I-III

    Energy Technology Data Exchange (ETDEWEB)

    Neumann, C.H.

    1986-10-01

    Between 1978 and 1983, 80 patients with Hodgkin's disease (HD) in clinical Stage I-III had computed tomography (CT) of the abdomen and pelvis and lymphography (LAG) prior to staging laparatomy with multiple lymph node biopsies at Stanford University Medical Center. There were 224 biopsied nodal sites. The sensitivity and specificity for CT to determine the status of biopsied paraortic and iliac nodes was .61 and .91 vs. .94 and .90 for LAG. CT appeared of even lower sensitivity (.13) in evaluating splenic hilar, celiac axis and portal nodes. Including all biopsy proven subdiaphragmatic nodal sites, CT's sensitivity to diagnose the presence of subdiaphragmatic adenopathy was .38 vs. .52 in LAG. Assessment of the final pathological stage was more successful by LAG (.61) than by CT (.49). Positive and negative predictive values of both tests indicate higher reliability of LAG results as regards individual intraabdominal nodes (LAG .71, .98 vs. CT .58, .86), the entire subdiaphragmatic nodal area (LAG .79, .77 vs. CT .61, .71) and prediction of final pathological stage. LAG appeared to be the more useful test during initial staging of newly diagnosed and untreated patients with HD. None of the test for itself or in combination can replace laparatomy when exact information is necessary for further clinical decisions.

  16. Long term results of mantle irradiation(MRT) alone in 261 patients with clinical stage I-II supradiaphragmatic Hodgkin's disease

    International Nuclear Information System (INIS)

    Wirth, A.; Byram, D.; Chao, M.; Corry, J.; Davis, S.; Kiffer, J.; Laidlaw, C.; Quong, G.; Ryan, G.; Liew, K.

    1997-01-01

    Purpose: We report our results using MRT for clinical stage I-II HD and assess the value of published prognostic criteria in our study population. Pts and Methods: Between 1969 and 1994, 261 pts were treated with MRT alone for clinical stage I-II supradiaphragmatic HD. Pt characteristics: median age-30; M-54%/F-46%; stage IA-52%, IB-2%, IIA-37%, IIB-8%; histology LP-21%, NS-51%, MC-23%, other 5%; median ESR 18. CT abdomen and LAG were performed in 61% and 60% respectively. No pt had prior staging laparotomy. No pt received infradiaphragmatic RT. Central axis dose was 32 Gy-36 Gy. Univariate analysis was performed for prognostic factors for progression-free (PFS) and overall survival(OS). Outcome was assessed in favourable subsets as defined by: EORTC (v. favourable: CSIA, LP or NS histology, age < 40, female, no bulk, ESR < 50; favourable: CSI-II, age < 50, < 4 sites, no bulky mediastinal mass, ESR < 50 with no B symptoms or ESR < 30 with B symptoms); Princess Margaret Hospital (PMH) (IA-IIA, LP or NS histology, ESR < 40, age < 50, no large mediastinal mass, no E lesion). Results: 261 pts completed RT, with 5% requiring treatment interruption for toxicity. Significant factors (P<0.05) for PFS were stage, performance status, histology, B symptoms, number of sites, ESR and bulk. Significant factors (P<0.05) for OS were age, performance status, histology and B symptoms. (The results of a multivariate analysis will be presented.) Results in our study population using published prognostic criteria (in %): Thirty-six percent progressed following RT: 8% in-field; 24% out of field only (including 10% in the paraaortic/splenic region alone); 4% marginal; Fifty-seven percent of relapsed pts remain progression free after subsequent salvage treatment. Two cases of acute leukaemia, 8 cases of non-Hodgkin's lymphoma and 14 (non-skin) carcinomas occurred, of which 11 were in-field. Seventy pts have died. The cause was: HD 41%; other malignancy 20%; cardiovascular 17%; other 15

  17. Prognostic impact of concomitant p53 and PTEN on outcome in early stage (FIGO I-II) epithelial ovarian cancer.

    Science.gov (United States)

    Skírnisdóttir, Ingirídur; Seidal, Tomas

    2011-08-01

    The objective of the study was to evaluate the prognostic effect of p53, PTEN, and concomitant p53 PTEN status on clinicopathologic features, recurrent disease, and disease-free survival (DFS) of 131 patients in FIGO stages I to II with epithelial ovarian cancer. The technique of tissue microarray and immunohistochemistry was used for the detection of positivity of the biologic markers p53 and PTEN. In the complete series, the 5-year DFS rate was 68%, and the overall survival rate was 71%. Positive staining for p53 and PTEN was detected in 25% and 22% of cases, respectively. Positivity of p53 was associated with tumor grade in the total series but not in the subgroup of serous tumors. In survival analysis, there was worse survival (P = 0.003) in the group of patients with p53-positive tumors compared with the group of patients with p53-negative tumors with DFS of 62% and 82%, respectively. Furthermore, DFS was 15% for the subgroup of patients with concomitant p53-positivity and PTEN-negativity of tumors compared with DFS of 62% for others in 1 group (p53+PTEN+, p53-PTEN+, p53-PTEN-) at 100 months. The difference was highly significant (P = 0.006). FIGO stage (odds ratio = 8.0) and p53 PTEN status (odds ratio = 0.6) were predictive factors for tumor recurrences in a logistic regression and prognostic factors with hazard ratios (HRs) of 4.0 and 0.6, respectively, in a multivariate Cox regression analysis. In a separate Cox regression analysis, FIGO stage (HR = 3.6) and p53 status (HR = 2.0) were prognostic factors for DFS. For serous tumors (n = 51) recurrent disease was associated with FIGO stage (P = 0.013), and p53 loss (P = 0.029) but not with FIGO grade (P = 0.169). p53 status divides ovarian carcinomas into 2 subgroups after prognosis, also in serous tumors. Presence of PTEN in p53-positive tumors seems to protect from bad prognosis and absence of PTEN seems to worsen prognosis in early stages.

  18. The effects of inpatient exercise therapy on the length of hospital stay in stages I-III colon cancer patients: randomized controlled trial.

    Science.gov (United States)

    Ahn, Ki-Yong; Hur, Hyuk; Kim, Dong-Hyun; Min, Jihee; Jeong, Duck Hyoun; Chu, Sang Hui; Lee, Ji Won; Ligibel, Jennifer A; Meyerhardt, Jeffrey A; Jones, Lee W; Jeon, Justin Y; Kim, Nam Kyu

    2013-05-01

    This study aimed to examine the effects of a postsurgical, inpatient exercise program on postoperative recovery in operable colon cancer patients We conducted the randomized controlled trial with two arms: postoperative exercise vs. usual care. Patients with stages I-III colon cancer who underwent colectomy between January and December 2011 from the Colorectal Cancer Clinic, were recruited for the study. Subjects in the intervention group participated in the postoperative inpatient exercise program consisted of twice daily exercise, including stretching, core, balance, and low-intensity resistance exercises. The usual care group was not prescribed a structured exercise program. The primary endpoint was the length of hospital stay. Secondary endpoints were time to flatus, time to first liquid diet, anthropometric measurements, and physical function measurements. A total of 31 (86.1 %) patients completed the trial, with adherence to exercise interventions at 84.5 %. The mean length of hospital stay was 7.82 ± 1.07 days in the exercise group compared with 9.86 ± 2.66 days in usual care (mean difference, 2.03 days; 95 % confidence interval (CI), -3.47 to -0.60 days; p = 0.005) in per-protocol analysis. The mean time to flatus was 52.18 ± 21.55 h in the exercise group compared with 71.86 ± 29.2 h in the usual care group (mean difference, 19.69 h; 95 % CI, -38.33 to -1.04 h; p = 0.036). Low-to-moderate-intensity postsurgical exercise reduces length of hospital stay and improves bowel motility after colectomy procedure in patients with stages I-III colon cancer.

  19. Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Matthew W., E-mail: matthew.jackson@ucdenver.edu [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Rusthoven, Chad G.; Jones, Bernard L. [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Kamdar, Manali [Department of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Rabinovitch, Rachel [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States)

    2016-01-01

    Background: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes. Methods and Materials: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed. Results: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010. Conclusion: This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage

  20. Pretreatment prognostic factors in patients with early-stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy alone

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Milicic, Biljana; Dagovic, Aleksandar; Acimovic, Ljubisa; Milisavljevic, Slobodan

    2006-01-01

    Purpose: To investigate influence of various pretreatment prognostic factors in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. Patients and Methods: One hundred and sixteen patients were treated with tumor doses of 69.6 Gy, 1.2-Gy, twice-daily fractionation. There were 49 patients with Stage I and 67 patients with Stage II. Eighty patients had Karnofsky performance status (KPS) 90-100 and 95 patients had <5% weight loss. Peripheral tumors were observed in 57 patients. Squamous histology was observed in 70 patients and the majority of patients had concomitant disease (n = 72). Results: The median survival time for all patients was 29 months; 5-year survival was 29%. The median time to local progression and the distant metastasis were not achieved, whereas 5-year local progression-free and distant metastasis-free survivals were 50% and 72%, respectively. Multivariate analysis identified KPS, weight loss, location, histology, and the reason for not undergoing surgery as prognostic factors for survival. KPS, location, and histology influenced local progression-free survival, whereas only KPS and weight loss influenced distant metastasis-free survival. Conclusions: This retrospective analysis identified KPS and weight loss as the most important prognostic factors of outcome in patients with early-stage NSCLC treated with hyperfractionation radiation therapy

  1. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix.

    Science.gov (United States)

    Maruyama, Y; VanNagell, J R; Yoneda, J; Donaldson, E; Gallion, H; Rowley, K; Kryscio, R; Beach, J L

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  2. Dose to heart substructures is associated with non-cancer death after SBRT in stage I-II NSCLC patients.

    Science.gov (United States)

    Stam, Barbara; Peulen, Heike; Guckenberger, Matthias; Mantel, Frederick; Hope, Andrew; Werner-Wasik, Maria; Belderbos, Jose; Grills, Inga; O'Connell, Nicolette; Sonke, Jan-Jakob

    2017-06-01

    To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). 803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively. Median follow-up was 34.8months. Two year Kaplan-Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009-197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003-70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death. Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Macrophage Inhibitory Cytokine-1 (MIC-1 as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuning LIU

    2016-04-01

    Full Text Available Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1, member of transforming growth factor-β (TGF-β superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC. Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001 and benign pulmonary disease patients (P<0.001. A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001, female (P=0.03 and T2 (P=0.022. A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%. Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

  4. A single-institution retrospective analysis of outcomes for stage I-II primary mediastinal large B-cell lymphoma treated with immunochemotherapy with or without radiotherapy.

    Science.gov (United States)

    Binkley, Michael S; Hiniker, Susan M; Wu, Sharon; Natkunam, Yasodha; Mittra, Erik S; Advani, Ranjana H; Hoppe, Richard T

    2016-01-01

    As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes.

  5. Clinical significance of perineural invasion diagnosed by immunohistochemistry with anti-S100 antibody in Stage I-III colorectal cancer.

    Science.gov (United States)

    Shimada, Yoshifumi; Kido, Tomoki; Kameyama, Hitoshi; Nakano, Mae; Yagi, Ryoma; Tajima, Yosuke; Okamura, Takuma; Nakano, Masato; Nagahashi, Masayuki; Kobayashi, Takashi; Minagawa, Masahiro; Kosugi, Shin-Ichi; Wakai, Toshifumi; Ajioka, Yoichi

    2015-12-01

    Perineural invasion (PN) diagnosed by hematoxylin-eosin (HE) staining is an important prognostic factor after curative-intent surgery in patients with colorectal cancer. However, the clinical significance of PN diagnosed by immunohistochemistry (IHC) has not been investigated. The present study assessed the clinical significance of PN diagnosed by IHC with an anti-S100 antibody in patients with colorectal cancer. We retrospectively enrolled 184 consecutive patients with stage I-III colorectal cancer who had undergone curative-intent surgery. We analyzed the absence/presence of PN diagnosed by HE staining (HE-PN) compared to that diagnosed by IHC with the anti-S100 antibody (S100-PN). Potential prognostic factors were identified by univariate and multivariate analyses of the overall and relapse-free survival. The [Formula: see text] statistics were used to assess the inter-observer reproducibility. The incidence of HE-PN and S100-PN among the 184 patients was 60 patients (32.6%) and 113 patients (61.4%), respectively (P colorectal cancer. An inter-observer assessment showed superior judgment reproducibility for S100-PN compared with HE-PN.

  6. Impact of 18F-fluoro-2-deoxyglucose positron emission tomography on treatment strategy and radiotherapy planning for stage I-II Hodgkin disease: a prospective multicenter study.

    Science.gov (United States)

    Pommier, Pascal; Dussart, Sophie; Girinsky, Théodore; Chabaud, Sylvie; Lagrange, Jean Leon; Nguyen, Tan Dat; Beckendorff, Véronique; D'Hombres, Anne; Artignan, Xavier; Bondiau, Pierre Yves; Carrie, Christian; Giammarile, Francesco

    2011-03-01

    To quantify the impact of preradiotherapy 18F-fluoro-2-deoxyglucose positron-emission tomography (FDG-PET) on treatment strategy and radiotherapy planning for patients with Stage I/II Hodgkin disease included in a large prospective multicenter study. Conventional computed tomography and FDG-PET were performed just before the planned radiotherapy. The radiotherapy plan was first elaborated under blinded conditions for FDG-PET data. Then, the medical staff was asked to confirm or not confirm the treatment strategy and, if appropriate, to modify the radiotherapy plan based on additional information from FDG-PET. Between January 2004 and January 2006, 137 patients were included (124 were available for analysis) in 11 centers (108 adults, 16 children). All but 1 patient had received chemotherapy before inclusion. Prechemotherapy work-up included FDG-PET for 61 patients, and data were available for elaboration of the first radiotherapy plan. Based on preradiotherapy FDG-PET data, the radiotherapy was cancelled in 6 patients (4.8%), and treatment plan modifications occurred in 16 patients (12.9%): total dose (11 patients), CTV volume (5 patients), number of beam incidences (6 patients), and number of CTV (6 patients). The concordance between the treatment strategies with or without preradiotherapy FDG-PET was 82.3%. Concordance results were not significantly different when prechemotherapy PET-CT information was available. Preradiotherapy FDG-PET for treatment planning in Hodgkin lymphoma may lead to significant modification of the treatment strategy and the radiotherapy planning in patients with Stage I or II Hodgkin disease, even in those who have undergone FDG-PET as part of the prechemotherapy work-up. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Adam J., E-mail: adam_olszewski@brown.edu; Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  8. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    International Nuclear Information System (INIS)

    Olszewski, Adam J.; Desai, Amrita

    2014-01-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas

  9. Comparative effect of 2 packages of pelvic floor muscle training on the clinical course of stage I-III pelvic organ prolapse.

    Science.gov (United States)

    Kashyap, Rashmi; Jain, Vanita; Singh, Amarjeet

    2013-04-01

    To compare the effect of 2 packages of pelvic floor muscle training (PFMT) on the clinical course of pelvic organ prolapse (POP) among women attending a gynecology outpatient department in Chandigarh, India. A randomized controlled trial was conducted between August 8, 2010, and October 31, 2011. Overall, 140 women with stage I-III POP were allocated to a 24-week behavioral therapy intervention. Group A (n=70) received 1-to-1 PFMT and a self-instruction manual (SIM), whereas Group B (n=70) received SIM alone. Symptoms were assessed using the POP symptom scale (POP-ss), visual analog scale (VAS), and pelvic floor impact questionnaire-7 (PFIQ-7) scores. Marked improvements in mean POP-ss, VAS, PFIQ-7 scores were observed in both groups from baseline to week 24. However, significant between-group changes in mean POP-ss scores were observed from baseline to 6 weeks (P<0.001), 18 weeks (P=0.001), and 24 weeks (P=0.002). Significant between-group changes in mean VAS scores were observed at 18 and 24 weeks (P=0.009 and P=0.005). Significant between-group changes in mean PFIQ-7 scores were observed at 6 (P=0.001), 18 (P<0.001), and 24 weeks (P<0.001). Provision of both 1-to-1 PFMT and SIM led to greater improvements in POP symptoms than provision of SIM alone. ctri.nic.in: CTRI/2010/091/001190. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Development of a nomogram combining clinical staging with 18F-FDG PET/CT image features in non-small-cell lung cancer stage I-III

    International Nuclear Information System (INIS)

    Desseroit, Marie-Charlotte; Visvikis, Dimitris; Majdoub, Mohamed; Hatt, Mathieu; Tixier, Florent; Perdrisot, Remy; Cheze Le Rest, Catherine; Guillevin, Remy

    2016-01-01

    Our goal was to develop a nomogram by exploiting intratumour heterogeneity on CT and PET images from routine 18 F-FDG PET/CT acquisitions to identify patients with the poorest prognosis. This retrospective study included 116 patients with NSCLC stage I, II or III and with staging 18 F-FDG PET/CT imaging. Primary tumour volumes were delineated using the FLAB algorithm and 3D Slicer trademark on PET and CT images, respectively. PET and CT heterogeneities were quantified using texture analysis. The reproducibility of the CT features was assessed on a separate test-retest dataset. The stratification power of the PET/CT features was evaluated using the Kaplan-Meier method and the log-rank test. The best standard metric (functional volume) was combined with the least redundant and most prognostic PET/CT heterogeneity features to build the nomogram. PET entropy and CT zone percentage had the highest complementary values with clinical stage and functional volume. The nomogram improved stratification amongst patients with stage II and III disease, allowing identification of patients with the poorest prognosis (clinical stage III, large tumour volume, high PET heterogeneity and low CT heterogeneity). Intratumour heterogeneity quantified using textural features on both CT and PET images from routine staging 18 F-FDG PET/CT acquisitions can be used to create a nomogram with higher stratification power than staging alone. (orig.)

  11. Conservative surgery and radiotherapy for stage I/II breast cancer using lung density correction: 10-year and 15-year results

    International Nuclear Information System (INIS)

    Pierce, Lori J.; Griffith, Kent A.; Hayman, James A.; Douglas, Kathye R.; Lichter, Allen S.

    2005-01-01

    Purpose: Radiotherapy (RT) planning for breast cancer using lung density correction improves dose homogeneity. Its use obviates the need for a medial wedge, thus reducing scatter to the opposite breast. Although lung density correction is used at many centers in planning for early-stage breast cancer, long-term results of local control and survival have not been reported. Since 1984, we have used lung density correction for dose calculations at the University of Michigan. We now present our 10-year and 15-year results. Methods and Materials: The records of 867 patients with Stage I/II breast cancer treated with breast-conserving surgery and RT with or without systemic therapy were reviewed. Tangential fields delivering 45-50 Gy to the whole breast calculated using lung density correction were used. A boost was added in 96.8% of patients for a total median dose of 61.8 Gy. Results: With a median follow-up of 6.6 years (range, 0.2-18.9 years), 5-, 10-, and 15-year actuarial rates of in-breast tumor recurrence as only first failure were 2.2%, 3.6%, and 5.4%, respectively. With surgical salvage, the 15-year cumulative rate of local control was 99.7%. Factors that significantly predicted for increased rate of local recurrence in multivariate analysis were age ≤ 35 years, hazard ratio 4.8 (95% confidence interval [CI], 1.6-13.9) p = 0.004; negative progesterone receptor status, hazard ratio 6.8 (95% CI, 2.3-20.3) p = < 0.001; negative estrogen receptor status, hazard ratio 4.0 (95% CI, 1.5-11.1) p = 0.007; and lack of adjuvant tamoxifen therapy, hazard ratio 7.7 (95% CI, 1.7-33.3) p = 0.008. Relapse-free survival rates at 5, 10, and 15 years were 84.6%, 70.8%, and 55.9%, respectively; breast cancer-specific survival rates were 94.4%, 90.5%, and 86.9%, respectively; and corresponding estimates for overall survival were 89.7%, 75.7%, and 61.3%. Conclusions: Use of lung density correction was associated with high rates of local control, relapse-free survival, breast

  12. Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy

    Directory of Open Access Journals (Sweden)

    Versmessen Harijati

    2012-10-01

    Full Text Available Abstract Background Health-related quality of life (HRQOL assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR and hypofractionated tomotherapy (TT have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy. Methods A total of 121 stage I–II breast cancer patients who had undergone breast conserving surgery (BCS or mastectomy (MA were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle. Results On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms, nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better

  13. Electron and high-dose-rate brachytherapy boost in the conservative treatment of stage I-II breast cancer. First results of the randomized Budapest boost trial

    International Nuclear Information System (INIS)

    Polgar, C.; Fodor, J.; Orosz, Z.

    2002-01-01

    Background and Aims: To evaluate the effect of electron and high-dose-rate brachytherapy (HDR BT) boost on local tumor control (LTC), side effects and cosmesis after breast-conserving surgery (BCS) in a prospective randomized study. Patients and Methods: 207 women with stage I-II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either a boost to the tumor bed (n=104) or no further radiotherapy (n=103). Boost treatments consisted of either 16 Gy electron irradiation (n=52) or 12-14.25 Gy HDR BT (n=52). Breast cancer-related events, side effects, and cosmetic results were assessed. Results: At a median follow-up of 5.3 years, the crude rate of local recurrence was 6.7% (7/104) with and 15.5% (16/103) without boost. The 5-year probability of LTC, relapse-free survival (RFS), and cancer-specific survival (CSS) was 92.7% vs 84.9% (p=0.049), 76.6% vs 66.2% (p=0.044), and 90.4% vs. 82.1% (p=0.053), respectively. There was no significant difference in LTC between patients treated with electron or HDR BT boost (94.2% vs 91.4%; p=0.74). On multivariate analysis, patient age <40 years (RR: 4.53), positive margin status (RR: 4.17), and high mitotic activity index (RR: 3.60) were found to be significant risk factors for local recurrence. The incidence of grade 2-3 side effects was higher in the boost arm (17.3% vs 7.8%; p=0.03). However, the rate of excellent/good cosmetic results was similar for the two arms (85.6% vs 91.3%; p=0.14). Cosmesis was rated as excellent/good in 88.5% of patients treated with HDR BT and 82.7% of patients with electron boost (p=0.29). Conclusions: Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy. In spite of the higher incidence of late side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. Positive or close margin status, high mitotic activity index, and young patient age

  14. Second cancers after conservative surgery and radiation for stages I-II breast cancer: identifying a subset of women at increased risk

    International Nuclear Information System (INIS)

    Fowble, Barbara; Hanlon, Alexandra; Freedman, Gary; Nicolaou, Nicos; Anderson, Penny

    2001-01-01

    Purpose: To assess the risk and patterns of second malignancy in a group of women treated with conservative surgery and radiation in a relatively contemporary manner for early-stage invasive breast cancer, and to identify a subgroup of these women at increased risk for a second cancer. Methods and Materials: From 1978 to 1994, 1,253 women with unilateral Stage I-II breast cancer underwent wide excision, axillary dissection, and radiation. The median follow-up was 8.9 years, with 446 patients followed for ≥10 years. The median age was 55 years. Sixty-eight percent had T1 tumors and 74% were axillary-node negative. Radiation was directed to the breast only in 78%. Adjuvant therapy consisted of chemotherapy in 19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their association with the cumulative incidence of all second malignancies, contralateral breast cancer, and non-breast cancer malignancy were: age, menopausal status, race, family history, obesity, smoking, tumor size, location, histology, pathologic nodal status, region(s) treated with radiation, and the use and type of adjuvant therapy. Results: One hundred seventy-six women developed a second malignancy (87 contralateral breast cancers at a median interval of 5.8 years, and 98 non-breast cancer malignancies at a median interval of 7.2 years). Nine women had both a contralateral breast cancer and non-breast cancer second malignancy. The 5- and 10-year cumulative incidences of a second malignancy were 5% and 16% for all cancers, 3% and 7% for contralateral breast cancer, 3% and 8%, for all second non-breast cancer malignancies, and 1% and 5%, respectively, for second non-breast cancer malignancies, excluding skin cancers. Patient age was a significant factor for contralateral breast cancer and non-breast cancer second malignancy. Young age was associated with an increased risk of contralateral breast cancer, while older age was associated with an increased the risk of a second non-breast cancer

  15. Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

    International Nuclear Information System (INIS)

    Hata, Masaharu; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-01-01

    Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade ≥3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC

  16. Dose-volume histogram parameters of high-dose-rate brachytherapy for Stage I-II cervical cancer (≤4cm) arising from a small-sized uterus treated with a point A dose-reduced plan

    International Nuclear Information System (INIS)

    Nakagawa, Akiko; Noda, Shin-ei; Kubo, Nobuteru; Kuwako, Keiko; Nakano, Takashi; Ohno, Tatsuya; Saitoh, Jun-ichi

    2014-01-01

    We investigated the rectal dose-sparing effect and tumor control of a point A dose-reduced plan in patients with Stage I-II cervical cancer (≤4 cm) arising from a small-sized uterus. Between October 2008 and August 2011, 19 patients with Stage I-II cervical cancer (≤4 cm) were treated with external beam radiotherapy (EBRT) for the pelvis and CT-guided brachytherapy. Seven patients were treated with brachytherapy with standard loading of source-dwell positions and a fraction dose of 6 Gy at point A (conventional brachy-plan). The other 12 patients with a small uterus close to the rectum or small intestine were treated with brachytherapy with a point A dose-reduction to match D2cc of the rectum and <6 Gy as the dose constraint ('point A dose-reduced plan') instead of the 6-Gy plan at point A ('tentative 6-Gy plan'). The total doses from EBRT and brachytherapy were added up and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2). The median doses to the high-risk clinical target volume (HR-CTV) D90 in the conventional brachy-plan, tentative 6-Gy plan and point A dose-reduced plan were 62 GyEQD2, 80 GyEQD2 and 64 GyEQD2, respectively. The median doses of rectal D2cc in the corresponding three plans were 42 GyEQD2, 62 GyEQD2 and 51 GyEQD2, respectively. With a median follow-up period of 35 months, three patients developed Grade-1 late rectal complications and no patients developed local recurrence. Our preliminary results suggested that CT-guided brachytherapy using an individualized point A dose-reduced plan might be useful for reducing late rectal complications while maintaining primary tumor control. (author)

  17. Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.

    Science.gov (United States)

    Zhang, Lu; Yu, Qingzhao; Wu, Xiao-Cheng; Hsieh, Mei-Chin; Loch, Michelle; Chen, Vivien W; Fontham, Elizabeth; Ferguson, Tekeda

    2018-05-01

    To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations. Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score. Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51). Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.

  18. Adjuvant whole abdominal intensity modulated radiotherapy (IMRT) for high risk stage FIGO III patients with ovarian cancer (OVAR-IMRT-01) – Pilot trial of a phase I/II study: study protocol

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Jensen, Alexandra D; Sterzing, Florian; Munter, Marc W; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2007-01-01

    The prognosis for patients with advanced epithelial ovarian cancer remains poor despite aggressive surgical resection and platinum-based chemotherapy. More than 60% of patients will develop recurrent disease, principally intraperitoneal, and die within 5 years. The use of whole abdominal irradiation (WAI) as consolidation therapy would appear to be a logical strategy given its ability to sterilize small tumour volumes. Despite the clinically proven efficacy of whole abdominal irradiation, the use of radiotherapy in ovarian cancer has profoundly decreased mainly due to high treatment-related toxicity. Modern intensity-modulated radiation therapy (IMRT) could allow to spare kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. The OVAR-IMRT-01 study is a single center pilot trial of a phase I/II study. Patients with advanced ovarian cancer stage FIGO III (R1 or R2< 1 cm) after surgical resection and platinum-based chemotherapy will be treated with whole abdomen irradiation as consolidation therapy using intensity modulated radiation therapy (IMRT) to a total dose of 30 Gy in 1.5 Gy fractions. A total of 8 patients will be included in this trial. For treatment planning bone marrow, kidneys, liver, spinal cord, vertebral bodies and pelvic bones are defined as organs at risk. The planning target volume includes the entire peritoneal cavity plus pelvic and para-aortic node regions. The primary endpoint of the study is the evaluation of the feasibility of intensity-modulated WAI and the evaluation of the study protocol. Secondary endpoint is evaluation of the toxicity of intensity modulated WAI before continuing with the phase I/II study. The aim is to explore the potential of IMRT as a new method for WAI to decrease the dose to kidneys, liver, bone marrow while covering the peritoneal cavity with a homogenous dose, and to implement whole abdominal intensity-modulated radiotherapy into the adjuvant multimodal

  19. Slender CRC Columns

    OpenAIRE

    Aarup, Bendt; Jensen, Lars Rom; Ellegaard, Peter

    2005-01-01

    CRC is a high-performance steel fibre reinforced concrete with a typical compressive strength of 150 MPa. Design methods for a number of structural elements have been developed since CRC was invented in 1986, but the current project set out to further investigate the range of columns for which current design guides can be used. The columns tested had a slenderness varying from 1.11 to 12.76 and a reinforcement ratio (area of rebar to area of concrete) ranging from 0 to 8.8 %. A total of 77 te...

  20. Stereotactic ablative body radiotherapy (SABR): an alternative to surgery in stage I-II non-small-cell cancer of the lung?

    Science.gov (United States)

    Mirimanoff, René-Olivier

    2015-12-01

    For decades, surgery was considered to be the only standard therapy for early-stage non-small cell lung cancer (NSCLC). However stereotactic ablative body radiotherapy (SABR) has been used in a growing number of patients and institutions since the early 2000's. Initially this technique was intended mainly for patients who were deemed to be medically inoperable due to co-morbidities or who refused surgery, but more recently it has been applied to operable patients as well. Strict criteria for treatment planning, the use of high-technology equipment and the appropriate selection of dose based on tumor size and location are of paramount importance for a proper application of SABR. Under these conditions, SABR offers high control rates with a moderate risk of severe toxicity, quite comparable to those of modern surgery. This article reviews the basic principles of SABR, its practical aspects, the definition of biologically equivalent doses, the results in terms of tumor control, survival and toxicity and an attempt will be made to compare the results of SABR with those of surgery.

  1. Relationship between vitamin D and lung function, physical performance and balance on patients with stage I-III chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tuncay Yumrutepe

    2015-04-01

    Full Text Available Summary Objectives: vitamin D is important for muscle function and it affects different aspects of muscle metabolism. This study aim to determine whether serum 25(OH D levels are related to lung functions, physical performance and balance in patients with chronic obstructive pulmonary disease (COPD. Methods: in 90 patients with COPD and 57 healthy controls lung function tests, physical performance tests (time up and go, gait velocity test, sit-to-stand test, isometric strength, isokinetic strength, static (functional reach test and dynamic (time up and go balance tests and the association of 25(OHD levels with lung functions, physical performance and balance were evaluated. Results: the COPD patients had significantly more deficit in physical function and balance parameters, and in dynamic balance test (p<0.005. Isokinetic knee muscle strength (flexor and extensor in COPD patients was significantly lower than in the controls (p<0.05; FEV1 (p=0.008, FVC (p=0.02, FEV1/FVC (p=0.04, TLC (p=0.01 were lower in COPD patients with vitamin D deficiency [25(OH D less than 15ng/mL] than in COPD patients without vitamin D deficiency. Hand grip test (p=0.000 and isokinetic knee muscle strength (flexor and extensor (p<0.05 were also lower in COPD patients with vitamin D deficiency. Vitamin D deficiency was more pronounced in patients with stage III COPD (p<0.05. Conclusion: patients with COPD had worst physical functioning, poor balance and less muscle strength. Severe disturbed lung and peripheral muscle functions are more pronounced in COPD patients with vitamin D deficiency.

  2. Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial

    Science.gov (United States)

    2012-01-01

    Background TomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities. Methods The trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test. Results By May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05). Conclusions There were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need confirmation with longer

  3. Dose-volume histogram parameters of high-dose-rate brachytherapy for Stage I-II cervical cancer (≤4cm) arising from a small-sized uterus treated with a point A dose-reduced plan.

    Science.gov (United States)

    Nakagawa, Akiko; Ohno, Tatsuya; Noda, Shin-ei; Kubo, Nobuteru; Kuwako, Keiko; Saitoh, Jun-Ichi; Nakano, Takashi

    2014-07-01

    We investigated the rectal dose-sparing effect and tumor control of a point A dose-reduced plan in patients with Stage I-II cervical cancer (≤4 cm) arising from a small-sized uterus. Between October 2008 and August 2011, 19 patients with Stage I-II cervical cancer (≤4 cm) were treated with external beam radiotherapy (EBRT) for the pelvis and CT-guided brachytherapy. Seven patients were treated with brachytherapy with standard loading of source-dwell positions and a fraction dose of 6 Gy at point A (conventional brachy-plan). The other 12 patients with a small uterus close to the rectum or small intestine were treated with brachytherapy with a point A dose-reduction to match D2cc of the rectum and <6 Gy as the dose constraint ('point A dose-reduced plan') instead of the 6-Gy plan at point A ('tentative 6-Gy plan'). The total doses from EBRT and brachytherapy were added up and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2). The median doses to the high-risk clinical target volume (HR-CTV) D90 in the conventional brachy-plan, tentative 6-Gy plan and point A dose-reduced plan were 62 GyEQD2, 80 GyEQD2 and 64 GyEQD2, respectively. The median doses of rectal D2cc in the corresponding three plans were 42 GyEQD2, 62 GyEQD2 and 51 GyEQD2, respectively. With a median follow-up period of 35 months, three patients developed Grade-1 late rectal complications and no patients developed local recurrence. Our preliminary results suggested that CT-guided brachytherapy using an individualized point A dose-reduced plan might be useful for reducing late rectal complications while maintaining primary tumor control. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  4. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix; Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd; Porsch, Peter; Studnicka, Michael

    2015-01-01

    While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [de

  5. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily: high local control in early stage (I/II) non-small-cell lung cancer.

    Science.gov (United States)

    Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd; Porsch, Peter; Studnicka, Michael; Sedlmayer, Felix

    2015-03-01

    While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70%) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88%, while regional control was 100%. There were 10 patients (19%) who died of the tumor, and 18 patients (33%) died due to cardiovascular or pulmonary causes. A total of 11 patients (20%) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28%) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts.

  6. Evolving concepts in staging and treatment of colorectal cancer

    NARCIS (Netherlands)

    Sloothaak, D.A.M.

    2015-01-01

    For localized colorectal cancer (CRC), lymph node metastases are the most powerful prognostic factor for disease specific and overall survival. In the first part of the thesis, we explore the prognostic role of lymph nodes in patients with stage I/II colon cancer. In these patients, nodal metastases

  7. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Paracelsus Medizinische Privatuniversitaet, Institute for Research and Development of Advanced Radiation Technologies (radART), Salzburg (Austria); Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Porsch, Peter; Studnicka, Michael [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Pneumologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria)

    2014-09-23

    While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for < 2.5 cm, 79.2 Gy for 2.5-4.5 cm, 84.6 Gy for 4.5-6 cm, 90 Gy for > 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [German] Die Standardbehandlung fuer nichtkleinzellige Bronchialkarzinome (NSCLC) im Stadium I/II ist die Operation, wobei Radiotherapie fuer Patienten, die nicht operabel sind oder die Operation ablehnen, als Alternative

  8. Serial Determination of bcl-2 Major Breakpoint Region (MBR) Rearrangement, t(14;18) (q32;q21), in the Bone Marrow and Peripheral Blood for Stages I - III Follicular Lymphoma after Central Lymphatic Irradiation (CLI) - A Preliminary Report

    International Nuclear Information System (INIS)

    Ha, C.S.; Cabanillas, F.; Lee, M.; Besa, P.C.; McLaughlin, P.W.; Cox, J.D.

    1995-01-01

    Purpose/Objective: About (2(3)) of all cases of follicular lymphoma have rearrangement of bcl-2 MBR through t(14;18) (q32;q21). This arrangement could serve as a sensitive marker for follicular lymphoma cells. The objectives of this study are two fold: 1) To assess complete molecular response rate of stages I-III follicular lymphoma to CLI by detection of PCR amplifiable bcl-2 MBR rearrangement in the bone marrow and peripheral blood before and after CLI. 2) To assess the significance of the molecular response as a prognostic indicator. Materials and Methods: 13 patients with stages I-III follicular lymphoma were treated with CLI as a part of a prospective randomized protocol comparing CLI with chemotherapy. Bone marrow and peripheral blood samples were obtained from the patients before initiation of CLI. By using the PCR technique, the DNA sequences from the bone marrow and peripheral blood samples that flank the bcl-2 MBR involved in t(14;18) (q32;q21) were amplified. For the patients who had positive PCR result, bone marrow and blood samples were followed at regular intervals during and after CLI. The patients with negative PCR result prior to CLI did not have follow-up PCR analysis. The results of the PCR amplification were correlated with clinical findings. Results: All 13 patients achieved clinical complete response after CLI. No patient has relapsed with a median follow-up period of 11 months (range 5 to 24 months). Pretreatment PCR results are available in 13 patients for peripheral blood and in 9 patients for bone marrow. (7(13)) blood and (5(9)) bone marrow samples were PCR-positive for bcl-2 MBR rearrangement. All 5 patients with positive pretreatment bone marrow also had positive pretreatment peripheral blood. (6(7)) patients with positive pretreatment blood PCR converted to negative within 2,3,5,6,6, and 10 months from the 1st day of CLI. The 7th patient has no follow-up PCR available yet. Follow-up PCR results from the pretreatment bone

  9. The relationship of the angiogenesis regulators VEGF-A, VEGF-R1 and VEGF-R2 to p53 status and prognostic factors in epithelial ovarian carcinoma in FIGO-stages I-II.

    Science.gov (United States)

    Skirnisdottir, Ingiridur; Seidal, Tomas; Åkerud, Helena

    2016-03-01

    The aim of this study was to evaluate prognostic effect of the angiogenesis regulators VEGF-R1, VEGF-R2 and VEGF-A for recurrent disease and disease-free survival (DFS), and their relation to the apoptosis regulator p53, in 131 patients with FIGO-stages I-II with epithelial ovarian cancer. For the detection of positivity of the markers the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of positive staining for VEGF-R1 was 19%, for VEGF-R2 and VEGF-A, it was 77 and 70%, respectively. Positivity for p53 was detected in 25% of tumors. The total number of recurrences in the complete series was 34 out of 131 (26%) and 5-year disease-free survival (DFS) was 68%. Positive staining for VEGF-A (P=0.030), VEGF-R2 (P=0.011) and p53 (P=0.015) was found more frequently in type II tumors than in type I tumors. Patients with VEGF-R1 negative tumors had worse (P=0.021) DFS compared to patients with VEGF-R1 positive tumors. In two multivariate Cox analyzes with DFS as endpoint, FIGO-stage (HR=3.8), VEGF-R2 status (HR=0.4) and p53 status (HR=2.3), all were significant and independent prognostic factors. When the variables VEGF-R2 and p53 were replaced with the new variable VEGF-R2+p53-/other three combinations in one group, it was found that patients from that subgroup had 86% reduced risk of dying in disease (HR=0.24). Findings above, confirmed relationship between VEGF-R2 and VEGF-A and p53, respectively, with regard to recurrent disease and survival. Some findings from the present study are different from results from previous studies on the regulation of angiogenesis. Despite many trials with anti-angiogenic agents in the front line of ovarian cancer have shown to be positive for progression-free survival, no one has demonstrated an impact on overall survival. Therefore, one of the greatest challenges in ovarian cancer research, is to discover predictive and prognostic biomarkers.

  10. Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for Stage IIIA and Stage IIIB non-small cell lung cancer: results of a Phase I-II study by the GOTHA group

    Energy Technology Data Exchange (ETDEWEB)

    Alberto, P.; Mermillod, B. [Hopital Cantonal Geneve, Geneva (Switzerland); Mirimanoff, R.O.; Leyvraz, S.; Nagy-Mignotte, H.; Bolla, M.; Wellmann, D.; Moro, D.; Brambilla, E. [Hopital Cantonal Universitaire, Lausanne (Switzerland)

    1995-08-01

    The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy. (author).

  11. Tape Storage and CRC Protection

    CERN Document Server

    Ha, Karel

    2014-01-01

    Over 100 Petabytes of data is stored on several kind of physical support, namely disks and tapes. Data on any physical support or traveling on a data link (network, fibre channel...) can be subject to silent data corruption. A possible improvement is introducing end-to-end data integrity from the filesystem down to the tape layer. For the tape back-end it can be done by using Logical Block Protection, which computes and compares CRC checksum of every single block of data. During my work, I improved on-the-fly CRC calculation for the tape storage system, which was achieved by introducing a multithreaded implementation - a technique applicable to arbitrary CRC algorithm. Finally, I per...

  12. CRC concise encyclopedia of mathematics

    CERN Document Server

    Weisstein, Eric W

    2003-01-01

    Upon publication, the first edition of the CRC Concise Encyclopedia of Mathematics received overwhelming accolades for its unparalleled scope, readability, and utility. It soon took its place among the top selling books in the history of Chapman & Hall/CRC, and its popularity continues unabated. Yet also unabated has been the dedication of author Eric Weisstein to collecting, cataloging, and referencing mathematical facts, formulas, and definitions. He has now updated most of the original entries and expanded the Encyclopedia to include 1000 additional pages of illustrated entries. The accessibility of the Encyclopedia along with its broad coverage and economical price make it attractive to the widest possible range of readers and certainly a must for libraries, from the secondary to the professional and research levels. For mathematical definitions, formulas, figures, tabulations, and references, this is simply the most impressive compendium available.

  13. CRC handbook of modern telecommunications

    CERN Document Server

    Morreale, Patricia A

    2001-01-01

    This authoritative handbook, contributed to by a team of international experts, covers the most dynamic areas in the changing telecommunications landscape. Written for telecommunications specialists who implement the new technologies, The CRC Handbook of Modern Telecommunications is an excellent companion volume to the authors' The Telecommunications Handbook, but stands well on its own, as it extends the range of topics to include voice over Internet, traffic management, quality of service, and other dominant future trends. It is an indispensable reference for all professionals working in the

  14. Prognostic value of pretreatment serum carcinoembryonic antigen and squamous cell carcinoma antigen levels for patients with stage I-III non-small cell lung cancer treated with radiation therapy alone

    International Nuclear Information System (INIS)

    Saito, Yoshihiro; Mitsuhashi, Norio; Hayakawa, Kazushige

    1998-01-01

    Serum carcinoembryonic antigen (CEA) and serum squamous cell carcinoma antigen (SCC Ag) levels have been reported to be useful as prognostic factors, indicators of clinical response, and predictors for recurrence in patients with lung cancer treated by surgery or chemotherapy. We investigated whether pretreatment serum CEA and SCC Ag levels were useful as independent prognostic factors in patients with stage I to III non-small cell lung cancer who were treated with radiation therapy alone. The serum CEA and SCC Ag levels were measured in 158 and 47 patients, respectively, before radiation therapy. Serum CEA and SCC Ag levels were measured by sandwich radioimmunoassay using the CEA-RIA (radioimmunoassay) kit and the SCC-RIA kit. Serum CEA and SCC Ag levels were above reference values in 19% and 30% of the patients, respectively. The 5-year survival rates were significantly better for patients with a negative SCC Ag result than for those with positive SCC Ag levels (p=0.0001), though no significant difference in survival rates was seen by CEA positivity (p=0.25). SCC Ag positivity (p=0.0006) and stage (p=0.04) were the important prognostic factors, as determined by multivariate analyses. Pretreatment serum SCC Ag level may be useful as an independent prognostic factor in patients with stage I to III non-small cell lung cancer who are treated with radiation therapy alone. (author)

  15. [A Phase I/II Study of Chemotherapy Concurrent with Twice-daily Radiotherapy 
Schedules by Intensity Modulated Radiation Therapy Using Simultaneous Integrated Boost for Limited-stage Small Cell Lung Cancer].

    Science.gov (United States)

    You, Jing; Yu, Huiming; Song, Maxiaowei; Shi, Chen; Wang, Xiaohang; Zheng, Ye; Yu, Rong; Shi, Anhui; Zhu, Guangying

    2017-01-20

    Twice-daily radiation concurrent with chemotherapy is one of the standard methods for limited-stage small cell lung cancer. The study was to evaluate the feasibility of chemotherapy concurrent with dose-escalating twice-daily radiotherapy by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) approach in patients with limited-stage small cell lung cancer. Patients with limited-stage small cell lung cancer were included, treated with twice-daily radiotherapy by SIB-IMRT concurrent with chemotherapy of etoposide plus cisplatin. Dose escalation was conducted by "classical" 3+3 methods with three patients enrolled in each dose level. The therapeutic gross tumor volume (GTV) was treated according to three consecutive dose levels i.e., 45 Gy at 1.5 Gy twice daily, 50 Gy at 1.67 Gy twice daily and 54 Gy at 1.8 Gy twice daily. The planning target volume (PTV) received a dose of 45 Gy delivered in 30 fractions of 1.5 Gy. The primary endpoints were acute toxicities. The secondary endpoints included overall survival (OS), progression-free survival (PFS) and loco-regional failure-free survival (LRFFS) at 1-year of follow-up. Twenty men and six women were included. The median age was 52 (30-68) months. 12 patients experienced grade 2 acute esophagitis, and 1 patient developed grade 3 acute esophagitis. Only 3 patients developed Grade 2 pneumonitis. Grade 3 or higher radiation-related pneumonia was not observed. None died of treatment-related causes. With median follow-up of 11.2 months (3.2-36.2 months), 1-year OS, PFS and LRFFS were 89.0%, 51.0% and 85.0%, respectively. Dose escalation for twice-daily radiation concurrent with chemotherapy in LS-SCLC has been safely achieved up to 54 Gy for GTV using SIB-IMRT technique.

  16. The apoptosis regulators p53, bax and PUMA: Relationship and impact on outcome in early stage (FIGO I-II) ovarian carcinoma after post-surgical taxane-based treatment.

    Science.gov (United States)

    Skírnisdóttir, I; Seidal, T

    2012-03-01

    The objective of this study was to evaluate the prognostic effect of the apoptosis regulators p53, bax and PUMA for recurrent disease and disease-free survival (DFS) in a series of 105 patients in FIGO-stages I-II with epithelial ovarian cancer, all treated with post-surgical platinum-taxane chemotherapy. For the detection of positivity of the biological markers p53, bax and PUMA the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of p53 positivity was 24%, that of bax positivity was 83%, and strong positivity was found for PUMA (43%). The bax status was related to tumor grade (P=0.029). Positive staining for bax was related to strong positivity of PUMA in the tumors (P=0.004). The p53, bax or PUMA status alone or concomitant (p53 bax, p53 PUMA and bax PUMA) were not related to age, histopathological subtype, serous/non-serous tumors or type of the staging procedure at primary surgery. In survival analysis p53-positive tumors (P=0.014) and concomitant p53-positive and weak PUMA-positive tumors (P=0.015) were significantly correlated with shorter DFS. Concomitant p53-negative and bax-positive tumors were significantly correlated with longer survival (P=0.019). FIGO-stage (OR=6.0) and p53 status (OR=4.1) were predictive factors for tumor recurrence in logistic regression analysis and independent prognostic factors (HR=2.4 for both) in multivariate Cox regression analysis. In a separate Cox multivariate regression analysis the p53 bax status (HR=2.2) was an independent prognostic factor for DFS. The p53 PUMA status (HR=0.4) was not an independent prognostic factor, however, a borderline significance (P=0.07) was noted. Our results indicate that FIGO stage and p53 status alone were independent predictive factors for recurrence and prognostic factors for survival. Furthermore, p53 bax status was an independent prognostic factor for survival in this study.

  17. A Phase I/II Study of Chemotherapy Concurrent with Twice-daily Radiotherapy 
Schedules by Intensity Modulated Radiation Therapy Using Simultaneous Integrated Boost for Limited-stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jing YOU

    2017-01-01

    Full Text Available Background and objective Twice-daily radiation concurrent with chemotherapy is one of the standard methods for limited-stage small cell lung cancer. The study was to evaluate the feasibility of chemotherapy concurrent with dose-escalating twice-daily radiotherapy by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT approach in patients with limited-stage small cell lung cancer. Methods Patients with limited-stage small cell lung cancer were included, treated with twice-daily radiotherapy by SIB-IMRT concurrent with chemotherapy of etoposide plus cisplatin. Dose escalation was conducted by “classical” 3+3 methods with three patients enrolled in each dose level. The therapeutic gross tumor volume (GTV was treated according to three consecutive dose levels i.e., 45 Gy at 1.5 Gy twice daily, 50 Gy at 1.67 Gy twice daily and 54 Gy at 1.8 Gy twice daily. The planning target volume (PTV received a dose of 45 Gy delivered in 30 fractions of 1.5 Gy. The primary endpoints were acute toxicities. The secondary endpoints included overall survival (OS, progression-free survival (PFS and loco-regional failure-free survival (LRFFS at 1-year of follow-up. Results Twenty men and six women were included. The median age was 52 (30-68 months. 12 patients experienced grade 2 acute esophagitis, and 1 patient developed grade 3 acute esophagitis. Only 3 patients developed Grade 2 pneumonitis. Grade 3 or higher radiation-related pneumonia was not observed. None died of treatment-related causes. With median follow-up of 11.2 months (3.2-36.2 months, 1-year OS, PFS and LRFFS were 89.0%, 51.0% and 85.0%, respectively. Conclusion Dose escalation for twice-daily radiation concurrent with chemotherapy in LS-SCLC has been safely achieved up to 54 Gy for GTV using SIB-IMRT technique.

  18. CRC-cards for Product Modelling

    DEFF Research Database (Denmark)

    Hvam, Lars; Riis, Jesper; Hansen, Benjamin Loer

    2003-01-01

    , transportation, service and decommissioning. A main challenge when building product models is to collect and document the product related data, information and knowledge in a structured way. CRC cards are index cards (or computerized versions of these) which are used to record proposed classes, the behavior...... of the classes, their responsibilities, and their relationship to other classes (collaboration). CRC modelling gives an effective, low-tech method for domain-experts, programmers and users to work closely together to identify, structure, understand and document a product model. CRC cards were originally......This paper describes the CRC (class, responsibility, collaboration) modelling process for building product models. A product model is normally represented in an IT system which contains data, information and knowledge on industrial products and their life cycle properties e.g. manufacturing...

  19. hERG1 Channels and Glut-1 as Independent Prognostic Indicators of Worse Outcome in Stage I and II Colorectal Cancer: A Pilot Study.

    Science.gov (United States)

    Lastraioli, Elena; Bencini, Lapo; Bianchini, Elisa; Romoli, Maria Raffaella; Crociani, Olivia; Giommoni, Elisa; Messerini, Luca; Gasperoni, Silvia; Moretti, Renato; Di Costanzo, Francesco; Boni, Luca; Arcangeli, Annarosa

    2012-04-01

    There is a need to identify new markers to assess recurrence risk in early-stage colorectal cancer (CRC) patients. We explored the prognostic impact of ether-a-gò-gò-related gene 1 channels and some hypoxia markers, in patients with nonmetastatic (stage I, II, and III) CRC. The expression of hERG1, vascular endothelial growth factor A (VEGF-A), glucose transporter 1, carbonic anhydrase IX (CA-IX), epidermal growth factor receptor (EGF-R), and p53 was tested by immunohistochemistry in 135 patients. The median follow-up was 35 months. Clinicopathologic parameters and overall survival were evaluated. hERG1 displayed a statistically significant association with Glut-1, VEGF-A, CA-IX, and EGF-R; p53 with VEGF-A and CA-IX; Glut-1 with the age of the patients; and EGF-R with TNM and mucin content. TNM and CA-IX were prognostic factors at the univariate analysis; TNM, hERG1, and Glut-1, at the multivariate analysis. Risk scores calculated from the final multivariate model allowed to stratify patients into four different risk groups: A) stage I-II, Glut-1 positivity, any hERG1; B) stage I-II, Glut-1 and hERG1 negativity; C) stage I-II, Glut-1 negativity, hERG1 positivity; D) stage III, any Glut-1 and any hERG1. hERG1 positivity with Glut-1 negativity identifies a patient group with poor prognosis within stage I-II CRC. The possibility that these patients might benefit from adjuvant therapy, independently from the TNM stage, is discussed. More robust prognostic and predictive markers, supplementing standard clinical and pathologic staging, are needed for node-negative patients.

  20. Pseudomonas putida growing at low temperature shows increased levels of CrcZ and CrcY sRNAs, leading to reduced Crc-dependent catabolite repression.

    Science.gov (United States)

    Fonseca, Pilar; Moreno, Renata; Rojo, Fernando

    2013-01-01

    The Crc protein of Pseudomonas inhibits the expression of genes involved in the transport and assimilation of a number of non-preferred carbon sources when preferred substrates are available, thus coordinating carbon metabolism. Crc acts by binding to target mRNAs, inhibiting their translation. In Pseudomonas putida, the amount of free Crc available is controlled by two sRNAs, CrcY and CrcZ, which bind to and sequester Crc. The levels of these sRNAs vary according to metabolic conditions. Pseudomonas putida grows optimally at 30°C, but can also thrive at 10°C. The present work shows that when cells grow exponentially at 10°C, the repressive effect of Crc on many genes is significantly reduced compared with that seen at 30°C. Total Crc levels were similar at both temperatures, but those of CrcZ and CrcY were significantly higher at 10°C. Therefore, Crc-mediated repression may, at least in part, be reduced at 10°C because the fraction of Crc protein sequestered by CrcZ and CrcY is larger, reducing the amount of free Crc available to bind its targets. This may help P. putida to face cold stress. The results reported might help understanding the behaviour of this bacterium in bioremediation or rhizoremediation strategies at low temperatures. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  1. Wurtzite-derived ternary I?III?O2 semiconductors

    OpenAIRE

    Omata, Takahisa; Nagatani, Hiraku; Suzuki, Issei; Kita, Masao

    2015-01-01

    Ternary zincblende-derived I?III?VI2 chalcogenide and II?IV?V2 pnictide semiconductors have been widely studied and some have been put to practical use. In contrast to the extensive research on these semiconductors, previous studies into ternary I?III?O2 oxide semiconductors with a wurtzite-derived ?-NaFeO2 structure are limited. Wurtzite-derived ?-LiGaO2 and ?-AgGaO2 form alloys with ZnO and the band gap of ZnO can be controlled to include the visible and ultraviolet regions. ?-CuGaO2, which...

  2. hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy.

    Science.gov (United States)

    Muratori, Leonardo; Petroni, Giulia; Antonuzzo, Lorenzo; Boni, Luca; Iorio, Jessica; Lastraioli, Elena; Bartoli, Gianluca; Messerini, Luca; Di Costanzo, Francesco; Arcangeli, Annarosa

    2016-01-01

    The identification of early-stage colorectal cancer (CRC) with high risk of progression is one major clinical challenge, mainly due to lack of validated biomarkers. The aims of the present study were to analyze the prognostic impact of three molecular markers belonging to the ion channels and transporters family: the ether-à-go-go-related gene 1 (hERG1) and the calcium-activated KCa3.1 potassium channels, as well as the glucose transporter 1 (Glut-1); and to define the impact of adjuvant chemotherapy in conjunction with the abovementioned biomarkers, in a cohort of radically resected stage I-III CRC patients. The expressions of hERG1, KCa3.1, and Glut-1 were tested by immunohistochemistry on 162 surgical samples of nonmetastatic, stage I-III CRC patients. The median follow-up was 32 months. The association between biological markers, clinicopathological features, and survival outcomes was investigated by evaluating both disease-free survival and overall survival. Although no prognostic valence emerged for KCa3.1, evidence of a negative impact of hERG1 expression on survival outcomes was provided. On the contrary, Glut-1 expression had a positive impact. According to the results of the multivariate analysis, patients were stratified in four risk groups, based on TNM stage and hERG1/Glut-1 expression. After adjusting for adjuvant therapy, stage I and II, Glut-1-negative, and hERG1-positive patients showed the worst survival experience. This study strongly indicates that the combination of hERG1 positivity and Glut-1 negativity behaves as a prognostic biomarker in radically resected CRC patients. This combination identifies a group of stage I and II CRC patients with a bad prognosis, even worse than that of stage III patients, regardless of adjuvant therapy accomplishment.

  3. The Crc/CrcZ-CrcY global regulatory system helps the integration of gluconeogenic and glycolytic metabolism in Pseudomonas putida.

    Science.gov (United States)

    La Rosa, Ruggero; Nogales, Juan; Rojo, Fernando

    2015-09-01

    In metabolically versatile bacteria, carbon catabolite repression (CCR) facilitates the preferential assimilation of the most efficient carbon sources, improving growth rates and fitness. In Pseudomonas putida, the Crc and Hfq proteins and the CrcZ and CrcY small RNAs, which are believed to antagonize Crc/Hfq, are key players in CCR. Unlike that seen in other bacterial species, succinate and glucose elicit weak CCR in this bacterium. In the present work, metabolic, transcriptomic and constraint-based metabolic flux analyses were combined to clarify whether P. putida prefers succinate or glucose, and to identify the role of the Crc protein in the metabolism of these compounds. When provided simultaneously, succinate was consumed faster than glucose, although both compounds were metabolized. CrcZ and CrcY levels were lower when both substrates were present than when only one was provided, suggesting a role for Crc in coordinating metabolism of these compounds. Flux distribution analysis suggested that, when both substrates are present, Crc works to organize a metabolism in which carbon compounds flow in opposite directions: from glucose to pyruvate, and from succinate to pyruvate. Thus, our results support that Crc not only favours the assimilation of preferred compounds, but balances carbon fluxes, optimizing metabolism and growth. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. CRC standard curves and surfaces with Mathematica

    CERN Document Server

    von Seggern, David H

    2006-01-01

    Since the publication of the first edition, Mathematica® has matured considerably and the computing power of desktop computers has increased greatly. This enables the presentation of more complex curves and surfaces as well as the efficient computation of formerly prohibitive graphical plots. Incorporating both of these aspects, CRC Standard Curves and Surfaces with Mathematica®, Second Edition is a virtual encyclopedia of curves and functions that depicts nearly all of the standard mathematical functions rendered using Mathematica. While the easy-to-use format remains unchanged from the previ

  5. A Novel Least Significant Bit First Processing Parallel CRC Circuit

    OpenAIRE

    Xiujie Qu; Zhongkai Cao; Zhanjie Yang

    2013-01-01

    In HDLC serial communication protocol, CRC calculation can first process the most or least significant bit of data. Nowadays most CRC calculation is based on the most significant bit (MSB) first processing. An algorithm of the least significant bit (LSB) first processing parallel CRC is proposed in this paper. Based on the general expression of the least significant bit first processing serial CRC, using state equation method of linear system, we derive a recursive formula by the mathematical...

  6. Type I-II laryngeal cleft: clinical course and outcome.

    Science.gov (United States)

    Slonimsky, Guy; Carmel, Eldar; Drendel, Michael; Lipschitz, Noga; Wolf, Michael

    2015-04-01

    Laryngeal cleft (LC) is a rare congenital anomaly manifesting in a variety of symptoms, including swallowing disorders and aspirations, dyspnea, stridor and hoarseness. The mild forms (types I-II) may be underdiagnosed, leading to protracted symptomatology and morbidity. To evaluate the diagnostic process, clinical course, management and outcome in children with type I-II laryngeal clefts. We conducted a retrospective case analysis for the years 2005-2012 in a tertiary referral center. Seven children were reviewed: five boys and two girls ranging in age from birth to 5 years. The most common presenting symptoms were cough, aspirations and pneumonia. Evaluation procedures included fiber-optic laryngoscopy (FOL), direct laryngoscopy (DL) and videofluoroscopy. Other pathologies were seen in three children. Six children underwent successful endoscopic surgery and one child was treated conservatively. The postoperative clinical course was uneventful in most of the cases. Types I-II LC should be considered in the differential diagnosis of children presenting with protracted cough and aspirations. DL is crucial for establishing the diagnosis. Endoscopic surgery is safe and should be applied promptly when conservative measures fail.

  7. CrcZ and CrcX regulate carbon utilization in Pseudomonas syringae pathovar tomato strain DC3000

    Science.gov (United States)

    Small non-coding RNAs (ncRNAs) are important components of many regulatory pathways in bacteria and play key roles in regulating factors important for virulence. Carbon catabolite repression control is modulated by small RNAs (crcZ or crcZ and crcY) in Pseudomonas aeruginosa and Pseudomonas putida. ...

  8. Hereditary Colorectal Cancer (CRC Program in Latvia

    Directory of Open Access Journals (Sweden)

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  9. Manda d'hajje I-II : [luuletused] / Uku Masing

    Index Scriptorium Estoniae

    Masing, Uku, 1909-1985

    2001-01-01

    Tekst eesti ja inglise k. U. Masingu lühibiograafia eesti ja inglise k. lk. 75. Sisu: Manda d'hajje I-II ; "Lennata mõtles kord muinasmaa liblikas..." = "Once a fairyland butterfly thought it would fly..." ; "Sa oled mägi, mida kardavad me karjed..." = "You are the mountain that our herds fear..." ; "Ammu tõusnud koopast, sygavalt ja kaugelt..." = "Long since risen from a cave, deep and far away..." ; "Imelik, et Sinu silmad mind ei karda..." ; "Strange that Your eyes do not fear me..." ; "Ööl järveks laiud. Ja siis äkki tõusvad üles..." = "At night You grow into a lake. From its bed..." ; "Sinu keha tõuseb minu käsivartelt..." = "Your body rises from my arms to meet me..."

  10. A Novel Least Significant Bit First Processing Parallel CRC Circuit

    Directory of Open Access Journals (Sweden)

    Xiujie Qu

    2013-01-01

    Full Text Available In HDLC serial communication protocol, CRC calculation can first process the most or least significant bit of data. Nowadays most CRC calculation is based on the most significant bit (MSB first processing. An algorithm of the least significant bit (LSB first processing parallel CRC is proposed in this paper. Based on the general expression of the least significant bit first processing serial CRC, using state equation method of linear system, we derive a recursive formula by the mathematical deduction. The recursive formula is applicable to any number of bits processed in parallel and any series of generator polynomial. According to the formula, we present the parallel circuit of CRC calculation and implement it with VHDL on FPGA. The results verify the accuracy and effectiveness of this method.

  11. System applications CRC -Biomass + Coal; Aplicaciones Sistema CRC-Biomasa+Carbon

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    Main object of Phase I of the project is to analyse the technical-economic feasibility of the combined use of biomass and coal for power generation in the Spanish region of Andalusia, by means of new medium-size independent power plants or using biomass as supplementary fuel in existing large coal power plants, including: -Analysis and classification of biomass and coal resources in the region -Technical-economic study of conventional alternatives using the steam cycle -Analysis of efficiency improvement provided by advanced Rankine-cycle technologies, like the SMR cycle -Analysis of alternatives based on parallel combined cycles using gas turbines, including advanced solutions, like the EAPI and CRC-EAPI systems. -Description and evaluation of different biomass drying systems. -Description and evaluation of the three main biomass gasification systems currently under development: atmospheric direct, atmospheric indirect and pressurized. Main objects of Phase II of the project are to analyse a specific application of the EAPI system to a real cogeneration plant project and to analyse the application of the CRC2 system to a commercial supercritical power plant, including technical-economic study of both applications. (Author)

  12. Radiotherapeutic aspects of the treatment of adult patients with supradiaphragmatic Hodgkin's disease CS I/II. Pt. 1; Regarding the indications of primary and adjuvant radiotherapy. Fragen und Aspekte zur Radiotherapie bei erwachsenen Patienten mit lokalisierten supradiaphragmalen Stadien (CS I/II) eines Morbus Hodgkin. T. 1; Fragen und Aspekte zu den Indikationen einer primaeren und einer adjuvanten Radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Glanzmann, C. (Universitaetsspital, Klinik fuer Radio-Onkologie, Zurich (Switzerland)); Luetolf, U.M. (Universitaetsspital, Klinik fuer Radio-Onkologie, Zurich (Switzerland))

    1993-08-01

    Randomized studies of chemo- vs radiotherapy in patients with PS I/II A and some PS III A have shown conflicting results. Patients with supra-diaphragmatic Hodkin's disease and CS I/II can be subdivided according to radiotherapy as: 1. Patients with a very low or a low recurrence risk of approximately 10 to 20%: Patients less than 40 years old and CS I/II A NS/LP with less than three involved regions and no bulky mediastinal mass and an ESR below 30 mm. In the other patients, primary irradiation of an extended mantle field without a staging laparotomy is an acceptable primary treatment, achieving a recurrence-free survival rate of approximately 80%. Another option is a staging laparotomy with splenectomy and a mantle radiotherapy for PS I/II. Few groups prefer primary chemotherapy alone or some type of a reduced chemotherapy with lesser toxicity combined with localized radiotherapy and long-term observations of a larger group of patients after the last type of treatment have to confirm the excellent early results. 2. Patients with an intermediate recurrence risk of approximately 20 to 40%: Patients, who do not belong to group one or group 3. Patients less than 50 years old with CS I/II and an ESR less than 50 mm and without bulky mediastinal involvement and with one of the following signs: Three involved regions or MC or one B symptom. A patient with more than one of these signs or with two or three B symptoms should be classified in group 3. For these patients, we recommend staging laparotomy and radiotherapy if PS I/II or primary chemotherapy with or without radiotherapy of the involved regions. 3. Patients with a high recurrence risk (40% or higher): (Abstract Truncated)

  13. Colorectal cancer diagnosis in 2012: A new focus for CRC prevention--more serration, less inflammation

    NARCIS (Netherlands)

    East, James E.; Dekker, Evelien

    2013-01-01

    Knowledge of colorectal cancer (CRC) risks has been rebalanced in 2012. The 'serrated pathway' to CRC, exemplified by serrated polyposis syndrome, emphasizes the importance of serrated lesions. The dogma that patients with IBD are at high risk of CRC, however, might be overstated; optimizing CRC

  14. Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

    Science.gov (United States)

    Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

    2017-03-14

    BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 - and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation.

  15. Skin as marker for collagen type I/III ratio in abdominal wall fascia.

    Science.gov (United States)

    Peeters, E; De Hertogh, G; Junge, K; Klinge, U; Miserez, M

    2014-08-01

    An altered collagen metabolism could play an important role in hernia development. This study compared collagen type I/III ratio and organisation between hernia and control patients, and analysed the correlation in collagen type I/III ratio between skin and abdominal wall fascia. Collagen organisation was analysed in Haematoxylin-Eosin sections of anterior rectus sheath fascia, and collagen type I/III ratio, by crosspolarisation microscopy, in Sirius-Red sections of skin and anterior rectus sheath fascia, of 19 control, 10 primary inguinal, 10 recurrent inguinal, 13 primary incisional and 8 recurrent incisional hernia patients. Compared to control patients [7.2 (IQR = 6.8-7.7) and 7.2 (IQR = 5.8-7.9)], collagen type I/III ratio was significantly lower in skin and anterior rectus sheath fascia of primary inguinal [5.2 (IQR = 3.8-6.3) and 4.2 (IQR = 3.8-4.7)], recurrent inguinal [3.2 (IQR = 3.1-3.6) and 3.3 (IQR = 3-3.7)], primary incisional [3.5 (IQR = 3-3.9) and 3.4 (IQR = 3.3-3.6)] and recurrent incisional hernia [3.2 (IQR = 3.1-3.9) and 3.2 (IQR = 2.9-3.2)] patients; also incisional and recurrent inguinal hernia had lower ratio than primary inguinal hernia patients. Furthermore, collagen type I/III ratio was significantly correlated (r = 0.81; P fascia. Finally, collagen organisation was comparable between hernia and control patients. Furthermore, in both skin and abdominal wall fascia of hernia patients, collagen type I/III ratio was lower compared to control patients, with more pronounced abnormalities in incisional and recurrent inguinal hernia patients. Importantly, collagen type I/III ratio in skin was representative for that in abdominal wall fascia.

  16. Pepsinogen I/II ratio is related to glucose, triacylglycerol, and uric acid levels.

    Science.gov (United States)

    Tanaka, Muhei; Fukui, Michiaki; Kuroda, Masaaki; Yamazaki, Masahiro; Hasegawa, Goji; Oda, Yohei; Naito, Yuji; Toda, Hitoshi; Yoshikawa, Toshikazu; Nakamura, Naoto

    2012-04-01

    Under- and overnutrition are associated with a worse prognosis and constitute independent risk factors for morbidity and mortality. It is increasingly important to understand the factors that affect nutritional and metabolic statuses. The purpose of this study was to assess the relation between the pepsinogen I/II ratio and several biochemical markers. A cross-sectional study was performed in 1985 subjects who underwent a health screening test. Subjects had no medications for hyperuricemia, dyslipidemia, diabetes mellitus, or hypertension. All subjects were classified into two groups. Subjects with a pepsinogen I/II ratio below 3 were defined as having atrophic gastritis. The relations between the pepsinogen I/II ratio and several biochemical markers, including total cholesterol, triacylglycerol, uric acid, cholinesterase, and glucose levels, were evaluated. The presence of atrophic gastritis was significantly associated with age, smoking status, alcohol consumption, body mass index, and triacylglycerol, uric acid, cholinesterase, and hemoglobin levels. Multiple linear regression analysis demonstrated that the pepsinogen I/II ratio was an independent determinant of glucose level (β = 0.104, P < 0.0001), triacylglycerol level (β = 0.072, P = 0.0014), uric acid level (β = 0.048, P = 0.0138), and hemoglobin (β = 0.037, P = 0.0429) after adjustments for age, sex, smoking status, alcohol consumption, and body mass index. The pepsinogen I/II ratio was related to glucose, triacylglycerol, and uric acid levels. Such an association fosters the idea that a decreased pepsinogen I/II ratio seems favorable for the prevention of overnutrition. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey.

    Science.gov (United States)

    Longhurst, H J; Zanichelli, A; Caballero, T; Bouillet, L; Aberer, W; Maurer, M; Fain, O; Fabien, V; Andresen, I

    2017-04-01

    Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P < 0·001). Median total attack duration was 5·0 h and 9·0 h for patients with C1-INH-AAE versus C1-INH-HAE types I/II, respectively. © 2016 British Society for Immunology.

  18. Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: Results from two consecutive Phase I/II trials

    International Nuclear Information System (INIS)

    Kao, Johnny; Conzen, Suzanne D.; Jaskowiak, Nora T.; Song, David H.; Recant, Wendy; Singh, Rachana; Masters, Gregory A.; Fleming, Gini F.; Heimann, Ruth

    2005-01-01

    Purpose: The management of unresectable locally advanced breast cancer (ULABC) remains a major challenge because of the necessity both to treat local disease and to prevent distant disease. Two consecutive Phase I/II trials of concomitant chemotherapy and radiation (CRT) were performed to attempt to address both local and distant disease control in ULABC. This analysis focuses on rates of locoregional control and radiation-associated acute and late complications. Methods and materials: Thirty-three patients with unresectable locally advanced or inflammatory breast cancers (T4N0-3M0-1) or locally recurrent disease were treated with CRT on two consecutive Phase I/II trials. Radiotherapy consisted of 60-70 Gy to the breast or chest wall and 60 Gy to draining lymphatics in a week-on/week-off (WO/WO) schedule. Chemotherapy consisted of either continuous infusion or bolus paclitaxel ± vinorelbine. A subset analysis of 16 patients with nonmetastatic ULABC Stage IIIB-C (T4N0-3M0) was performed. Among this cohort, 13 patients (81%) underwent planned mastectomy after CRT. Results: Of the 16 patients with Stage IIIB-C disease, acute toxicity included moist desquamation (n = 8) and Grade 3-4 neutropenia (n = 3). Late toxicity included breast reconstruction loss, decreased range of arm motion, lymphedema, and skin toxicity, although none was life-threatening. Of 15 assessable patients, 14 had a clinical response, 7 had a pathologic complete response (pCR) including 6 of 13 patients undergoing mastectomy. With a median follow-up for living patients of 43.8 months, the 4-year actuarial locoregional control, disease-free survival, and overall survival were 83%, 33%, and 56% respectively. Conclusions: Concurrent WO/WO radiation therapy and paclitaxel ± vinorelbine is effective locoregional therapy for ULABC with an acceptable toxicity profile. Further investigation of concurrent chemoradiotherapy in ULABC is warranted

  19. Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial

    International Nuclear Information System (INIS)

    Allal, Abdelkarim S.; Bieri, Sabine; Bruendler, Marie-Anne; Soravia, Claudio; Gertsch, Philippe; Bernier, Jacques; Morel, Philippe; Roth, Arnaud D.

    2002-01-01

    Purpose: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. Methods and Materials: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. Results: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located ≤6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). Conclusion: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a

  20. Liver transplantation for glycogen storage disease types I, III, and IV

    NARCIS (Netherlands)

    Matern, D; Starzl, TE; Arnaout, W; Barnard, J; Bynon, JS; Dhawan, A; Emond, J; Haagsma, EB; Hug, G; Lachaux, A; Smit, GPA; Chen, YT

    1999-01-01

    Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy

  1. Seroprevalence of HTLV -I/II amongst Blood Donors in Osogbo ...

    African Journals Online (AJOL)

    Background: HTLV type I/II is a blood borne infection that can be transmitted via blood transfusion. Objective: To determine the seroprevalence of human T – lymphotropic virus among blood donors in Osogbo, Nigeria. Methods: Diagnosis of Human T. Lymphotropic virus antigen was carried out on 372 serum samples ...

  2. Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers

    NARCIS (Netherlands)

    de Cuba, E. M. V.; Snaebjornsson, P.; Heideman, D. A. M.; van Grieken, N. C. T.; Bosch, L. J. W.; Fijneman, R. J. A.; Belt, E.; Bril, H.; Stockmann, H. B. A. C.; Hooijberg, E.; Punt, C. J. A.; Koopman, M.; Nagtegaal, I. D.; Coupé, V. H. M.; Carvalho, B.; Meijer, G. A.

    2016-01-01

    Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear

  3. A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Suenaga M

    2015-03-01

    Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Keisho Chin,1 Toshiharu Yamaguchi2 1Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan Background: Triweekly capecitabine plus irinotecan (XELIRI is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI in metastatic colorectal cancer (mCRC because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV as second-line chemotherapy for mCRC.Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin and BV and had a UGT1A1 genotype of wild-type or heterozygous for UGT1A1*6 or *28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5 mg/kg on day 1 every 2 weeks. The phase I study consisted of two steps (irinotecan 150 and 180 mg/m2, and dose-limiting toxicity was assessed during the first treatment cycle. The primary endpoint of the phase II study was progression-free survival (PFS.  Results: The recommended dose of irinotecan was determined to be 180 mg/m2 in the phase I study. Between November 2010 and August 2013, 44 patients were enrolled in phase II. The patients’ characteristics were as follows (N=44: median age, 60 years (range 32–80; male/female, 21/23; and UGT1A1 wild-type/heterozygous, 29/15. The median PFS was 6.8 months (95% confidence interval, 5.3–8.2 months, and the primary endpoint was met. Median overall survival was 18.3 months. The response rate was 22.7%. There was no significant difference in PFS or overall survival according to UGT1A1 status. Grade 3 or higher adverse events were mainly neutropenia in six

  4. CRC-cards to support development and maintenance of product configuration systems

    DEFF Research Database (Denmark)

    Haug, Anders; Hvam, Lars

    2009-01-01

    and maintenance of PCSs. This procedure has since been applied in several configuration projects and further developed at the Centre for Product Modelling (CPM) at the Technical University of Denmark. However, the investigations of two companies that applies CRC cards to document the knowledge base of their PCSs...... showed that their CRC card layouts differ from the definitions by CPM in many respects. Therefore, this article proposes a new CRC card definition that incorporates the experiences from the studied cases together with other kinds of extensions. The proposed CRC-card definition improves the basis...

  5. Retracted: Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    2018-02-01

    Following on from the Expression of Concern (10.1002/glia.22466) previously published by GLIA, the following Original Article has been retracted by the journal Editors and Publisher: Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis By Milena Penkowa and Juan Hidalgo GLIA (2000), 32(3), 247-263 DOI: 10.1002/1098-1136(200012)32:33.0.CO;2-T Discrepancies in the type and number of animals used in experiments performed by Milena Penkowa and reported in Table 1, identified during the course of investigations into Ms Penkowa's research, render the data and conclusions drawn from them unreliable. © 2017 Wiley Periodicals, Inc.

  6. Dynamic fracture initiation in brittle materials under combined mode I/II loading

    International Nuclear Information System (INIS)

    Nakano, M.; Kishida, K.; Yamauchi, Y.; Sogabe, Y.

    1994-01-01

    A new test method has been developed to measure the resistance of dynamic fracture initiation in brittle materials under combined mode I/II loadings. The Brazilian disks with center-cracks have been fractured under oblique impact loadings in diametral-compression. The dynamic stress intensity factors of mode I and II are evaluated from the superposition integrals of the step response functions for the cracked disk. The experimental results are presented to elucidate the influence of loading rate on the combined mode fracture toughness for ceramics and glasses. (orig.)

  7. Rock Fracture Toughness Study Under Mixed Mode I/III Loading

    Science.gov (United States)

    Aliha, M. R. M.; Bahmani, A.

    2017-07-01

    Fracture growth in underground rock structures occurs under complex stress states, which typically include the in- and out-of-plane sliding deformation of jointed rock masses before catastrophic failure. However, the lack of a comprehensive theoretical and experimental fracture toughness study for rocks under contributions of out-of plane deformations (i.e. mode III) is one of the shortcomings of this field. Therefore, in this research the mixed mode I/III fracture toughness of a typical rock material is investigated experimentally by means of a novel cracked disc specimen subjected to bend loading. It was shown that the specimen can provide full combinations of modes I and III and consequently a complete set of mixed mode I/III fracture toughness data were determined for the tested marble rock. By moving from pure mode I towards pure mode III, fracture load was increased; however, the corresponding fracture toughness value became smaller. The obtained experimental fracture toughness results were finally predicted using theoretical and empirical fracture models.

  8. Relationship between protein complotypes and DNA variant haplotypes: complotype-RFLP constellations (CRC).

    Science.gov (United States)

    Simon, S; Truedsson, L; Marcus-Bagley, D; Awdeh, Z; Eisenbarth, G S; Brink, S J; Yunis, E J; Alper, C A

    1997-09-15

    From the study of 52 families and 15 homozygous typing cells, 234 MHC complement haplotypes were characterized for features in the DNA of the complotype region: C2/Sst I (2.75, 2.70, 2.65, and 2.40 kb), BF/Taq I (6.6 and 4.5 kb), C4 5'/Bgl II (15 and 4.5 kb), C4 5'/Taq I (7.0, 6.4, 6.0 and 5.4 kb) and C4 3'/Xba I/BamH I (11 and 4 + 7 kb) restriction fragment length polymorphisms (RFLP's), by the presence or absence of C4A, C4B, CYP21A and CYP21B genes and by duplications. Nineteen (of over 1000 theoretically possible) complotype-RFLP constellations (CRC's) were found. The 9 CRC's with two C4 and CYP21 genes were designated A through I. CRC's Bdup and Ddup were like B and D but had duplicated C4B-CYP21B genes. The remaining CRC's had deletions of C4 and/or CYP21 genes and were designated Bdel, Cdel and the like. Individual complement alleles and complotypes were nor randomly distributed among the CRC's. Some complotypes, such as SC01, SC02 and FIC30, were restricted to only 1 CRC; others, such as SC31, FC31, and SC30, were found in several CRC's. Some of the CRC's contained a single complotype, others contained several. Remarkably, there are about 30 CRC-specified complotypes with frequencies of .01 or higher and 14 of .02 or higher. A number of evolutionary origins of complement alleles and complotypes are suggested by the relationships among CRC's. Approximate normal frequencies of the undeleted CRC's were A = .27, B = .19, Bdup = .02, C = .17, D = .07, Ddup = .02, E = .06, F = .05, and G = .02. Thus, CRC's without deletions accounted for 88% of normal complotypes. Since the frequency of Bdel, with a deletion of C4A, was .12, 10 CRC's accounted for all observed normal caucasian MHC haplotypes.

  9. Phase I/II trial of concurrent use of S-1 and radiation therapy for T2 glottic cancer

    International Nuclear Information System (INIS)

    Nakayama, Meijin; Hayakawa, Kazushige; Okamoto, Makito; Niibe, Yuzuru; Ishiyama, Hiromichi; Kotani, Shouko

    2010-01-01

    A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events. In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m 2 , for a total daily dose of 80 mg/m 2 . The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation. Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2). The use of S-1 at 80 mg/m 2 per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life. (author)

  10. Effect of aging on mixed-mode I/III fracture toughness of 2034 aluminum alloys

    International Nuclear Information System (INIS)

    Kamat, S.V.; Hirth, J.P.

    1996-01-01

    The effect of aging on the mixed-mode I/III fracture toughness was evaluated for two 2034 Al type alloys with different Mn content. The effect of aging was found to be significantly different in the two alloys. Alloy 1 which had < 0.1 wt% Mn exhibited a significant reduction in fracture toughness with increasing mode III loading contribution. In this alloy, increasing aging time resulted in less reduction of fracture toughness with increasing mode III loading contribution. On the other hand, alloy 2 which had 1.08 wt% Mn exhibited a marginal effect of mixed-mode loading on fracture toughness. In this alloy increasing aging time did not result in a significant change in the mixed-mode fracture behavior. The results are discussed in light of the microstructures, fracture mechanisms and deformation field ahead of the crack tip under mixed-mode loading

  11. Data on HLA class I/II profile in Brazilian pemphigus patients

    Directory of Open Access Journals (Sweden)

    Maria José Franco Brochado

    2016-09-01

    Full Text Available Pemphigus are blistering autoimmune diseases related with genetic and environmental factors. Here we describe HLA genotyping in pemphigus patients. First, we review the HLA class I/II data on pemphigus reported in Brazilian samples and then present the HLA class I (-A, -B, -C and class II (-DRB1, -DQA1, -DQB1 alleles related to susceptibility/resistance to pemphigus by comparing 86 patients with pemphigus foliaceus, 83 patients with pemphigus vulgaris, and 1592 controls from the northeastern region of the state of São Paulo, Southeastern Brazil. The data presented here are related to the manuscript “Differential HLA class I and class II associations in Pemphigus Foliaceus and Pemphigus Vulgaris patients from a prevalent Southeastern Brazilian region” Brochado et al. (2016 [1].

  12. The Phase I/II BNCT Trials at the Brookhaven medical research reactor: Critical considerations

    International Nuclear Information System (INIS)

    Diaz, A.Z.

    2001-01-01

    A phase I/II clinical trial of boronophenylalanine-fructose (BPA-F) mediated boron neutron capture therapy (BNCT) for Glioblastoma Multiforme (GBM) was initiated at Brookhaven National Laboratory (BNL) in 1994. Many critical issues were considered during the design of the first of many sequential dose escalation protocols. These critical issues included patient selection criteria, boron delivery agent, dose limits to the normal brain, dose escalation schemes for both neutron exposure and boron dose, and fractionation. As the clinical protocols progressed and evaluation of the tolerance of the central nervous system (CNS) to BPA-mediated BNCT at the BMRR continued new specifications were adopted. Clinical data reflecting the progression of the protocols will be presented to illustrate the steps taken and the reasons behind their adoption. (author)

  13. Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC)

    DEFF Research Database (Denmark)

    Winther, Stine Braendegaard; Zubcevic, Kanita; Qvortrup, Camilla

    2016-01-01

    . In general, therapy was well tolerated; main non-hematological toxicities were fatigue and diarrhea. CONCLUSION: S-1 monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients. These regimens are now further evaluated......BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate......) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44...

  14. Preliminary results of a phase I/II study of HDR brachytherapy alone for T1/T2 breast cancer

    International Nuclear Information System (INIS)

    Wazer, David E.; Berle, Lisa; Graham, Roger; Chung, Maureen; Rothschild, Janice; Graves, Theresa; Cady, Blake; Ulin, Kenneth; Ruthazer, Robin; DiPetrillo, Thomas A.

    2002-01-01

    Purpose: To investigate the feasibility, toxicity, cosmetic outcome, and local control of high-dose-rate (HDR) brachytherapy alone without whole breast external beam irradiation for early-stage breast carcinoma. Methods and Materials: Between June 1997 and August 1999, 32 women diagnosed with a total of 33 AJCC Stage I/II breast carcinomas underwent surgical breast excision and postoperative irradiation using HDR brachytherapy interstitial implantation as part of a multi-institutional clinical Phase I/II protocol. Eligible patients included those with T1, T2, N0, N1 (≤3 nodes positive), and M0 tumors of nonlobular histologic features with negative surgical margins, no extracapsular lymph node extension, and a negative postexcision mammogram. Brachytherapy catheters were placed at the initial excision, reexcision, or either sentinel or full-axillary sampling. Direct visualization, surgical clips, and ultrasound and/or CT scan assisted in the delineation of the target volume, defined as the excision cavity plus a 2-cm margin. High-activity 192 Ir (3-10 Ci) was used to deliver 340 cGy/fraction, 2 fractions/d, for 5 consecutive days, to a total dose of 34 Gy to the target volume. Source position and dwell times were calculated using standard volume optimization techniques. Results: The median follow-up of all patients was 33 months, and the mean patient age was 63 years. The mean tumor size was 1.3 cm, and 55% had an extensive intraductal component. Three patients had positive axillary nodes. Two patients experienced moderate perioperative pain that required narcotic analgesics. No peri- or postoperative infections occurred. No wound healing problems and no significant skin reactions related to the implant developed. The Radiation Therapy Oncology Group late radiation morbidity scoring scheme was applied to the entire 33-case cohort. In the assessment of the skin, 30 cases were Grade 0-1 and 3 cases were Grade 2. Subcutaneous toxicity was scored as 11 patients with

  15. Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab.

    Science.gov (United States)

    Weber, Jeffrey; Gibney, Geoffrey; Kudchadkar, Ragini; Yu, Bin; Cheng, Pingyan; Martinez, Alberto J; Kroeger, Jodie; Richards, Allison; McCormick, Lori; Moberg, Valerie; Cronin, Heather; Zhao, Xiuhua; Schell, Michael; Chen, Yian Ann

    2016-04-01

    The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3-4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%-41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naïve and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3-4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%-82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3-4 immune-related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab. ©2016 American Association for Cancer Research.

  16. Phase I/II trial of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Fujii, Masato; Tsukuda, Mamoru; Kubota, Akira; Kida, Akinori; Okami, Kenji

    2003-01-01

    Docetaxel (DOC) is one of the most promising drugs for head and neck cancer (HNSCC). A phase I/II trial of concurrent DOC and radiation for HNSCC was conducted to estimate the recommended dose schedule of DOC, and then to evaluate the therapeutic benefit based on the response and toxicity of the recommended dose schedule. Patients with squamous cell carcinomas of the head and neck were entered. All the patients received radiation with 2.0 Gy single daily fractions up to 60 Gy. DOC was administered weekly for 6 consecutive weeks during radiotherapy. Dose-limiting toxicities, grade 3/4 mucositis and grade 3 pain, manifested in four patients in level 2, and that dose of DOC, 15 mg/m 2 , was considered the maximum tolerated dose (MTD). The recommended dose was decided as 10 mg/m 2 . The phase II study was conducted using DOC at 10 mg/m 2 . Thirty-nine patients with stage II, III or IV were registered, and 35 patients were eligible, 32 patients were evaluable for the response and 34 patients for the toxicity. The overall response rate was 96.9%. The prognoses of the complete response (CR) patients were statistically better than for the partial response (PR) patients. Grade 3 or 4 adverse events consisted of lymphopenia in 64.7%, mucositis in 41.2% and anorexia in 20.6% of the patients. Thirty-two of the 35 eligible patients showed high compliance of over 90%, and their toxicities were manageable. Even low-dose DOC shows a strong effect on HNSCC in combination with radiation, with high survival rates in CR patients. The effect on survival will be assessed by further follow-up. (author)

  17. Structural changes induced by thermal annealing in Cr/C multilayers

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Yuchun [MOE Key Laboratory of Advanced Micro-structured Materials, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Sorbonne Universités, UPMC Univ Paris 06, Laboratoire de Chimie Physique-Matière et Rayonnement, 11 rue Pierre et Marie Curie, F-75231 Paris cedex 05 (France); CNRS UMR 7614, Laboratoire de Chimie Physique-Matière et Rayonnement, 11 rue Pierre et Marie Curie, F-75231 Paris cedex 05 (France); Zhu, Jingtao, E-mail: jtzhu@tongji.edu.cn [MOE Key Laboratory of Advanced Micro-structured Materials, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Li, Haochuan [MOE Key Laboratory of Advanced Micro-structured Materials, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Jonnard, Philippe; Le Guen, Karine; André, Jean-Michel [Sorbonne Universités, UPMC Univ Paris 06, Laboratoire de Chimie Physique-Matière et Rayonnement, 11 rue Pierre et Marie Curie, F-75231 Paris cedex 05 (France); CNRS UMR 7614, Laboratoire de Chimie Physique-Matière et Rayonnement, 11 rue Pierre et Marie Curie, F-75231 Paris cedex 05 (France); Chen, Hong [MOE Key Laboratory of Advanced Micro-structured Materials, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Wang, Zhanshan, E-mail: wangzs@tongji.edu.cn [MOE Key Laboratory of Advanced Micro-structured Materials, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China)

    2014-09-15

    Highlights: • We reported experimental results on thermal effects of Cr/C multilayer. • The period thicknesses of Cr/C multilayers expand or contract with different carbon layer thickness ratios upon 600 °C annealing. • More chromium carbide formed at the interfaces after annealing. - Abstract: The structural changes induced by thermal annealing in Cr/C multilayers were investigated. Cr/C multilayers with period thickness of 5 nm and bi-layer number of 30 were deposited by direct current magnetron sputtering, and characterized by using grazing incidence X-ray reflectivity, X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The results suggest that the period thicknesses of Cr/C multilayers expand or contract with different carbon layer thickness ratios (the ratio of the carbon layer thickness to the multilayer period) upon annealing and the physical mechanism was explored in detail. Carbon layer in Cr/C multilayers become graphitized from amorphous state. Such graphitization of the carbon layer causes a decrease in its density, thus an increase in its thickness. The annealing process also causes a reduction in period due to the formation of denser carbide, which can be confirmed by the XPS results.

  18. Quality of Sleep and Related Factors During Chemotherapy in Patients with Stage I/II Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hsiao-Hsuan Kuo

    2006-01-01

    Conclusion: The study showed poor sleep quality and daytime sleepiness in patients with breast cancer during the active phase of chemotherapy. Chemotherapy may bring symptom distress to patients and adversely influence sleep quality.

  19. Treatment of large stage I-II lung tumors using stereotactic body radiotherapy (SBRT): Planning considerations and early toxicity

    International Nuclear Information System (INIS)

    Ong, Chin Loon; Palma, David; Verbakel, Wilko F.A.R.; Slotman, Ben J.; Senan, Suresh

    2010-01-01

    Purpose: To study the dosimetric predictors of early clinical toxicity following SBRT in patients with lung tumors and planning target volumes (PTV) exceeding 80 cm 3 . Methods: Eighteen consecutive patients who were treated using volumetric modulated arc therapy (RapidArc TM ) were assessed. All were either unfit or refused to undergo surgery or chemoradiotherapy. PTV planning objectives were as used in the ROSEL study protocol. Clinical toxicity was scored using Common Toxicity Criteria AE4.0. Lung volumes receiving 5, 10, 15, and 20 Gy (V 5 , V 10 , V 15 and V 20 ) and mean lung dose were assessed and correlated to symptomatic radiation pneumonitis (RP). Results: Median age, age-adjusted Charlson-comorbidity score and PTV size were 74, 7.5 and 137 cm 3 , respectively. At a median follow-up of 12.8 months, 8 deaths were recorded: 5 arising from comorbidity, 2 were potentially treatment-related and 1 had local recurrence. RP was reported in 5 patients (grade 2 in 3 and grade 3 in 2). All RP occurred in plans without a high priority optimization objective on contralateral lung. Acute RP was best predicted by contralateral lung V 5 (p 80 cm 3 , the contralateral lung V 5 best predicts RP. Limiting contralateral lung V 5 to <26% may reduce acute toxicity.

  20. Clinical evaluation of Lugol's iodine staining in the treatment of stage I-II squamous cell carcinoma of the tongue.

    Science.gov (United States)

    Umeda, M; Shigeta, T; Takahashi, H; Minamikawa, T; Komatsubara, H; Oguni, A; Shibuya, Y; Komori, T

    2011-06-01

    Oral squamous cell carcinoma (OSCC) is often surrounded by epithelial dysplasia; leaving it unresected can result in local recurrence. Staining with Lugol's iodine solution detects epithelial dysplasia in oral mucosa, but whether it decreases local recurrence after OSCC surgery is unknown. This study investigated local recurrence rates in patients with early tongue cancer who underwent surgery using Lugol's staining. 93 patients with T1-2N0 tongue SCC underwent partial glossectomy using Lugol's staining during surgery. Resection was performed at least 5mm from the margin of the unstained area. Patients were investigated retrospectively for local recurrence status. Postoperative histology revealed negative surgical margins for SCC or epithelial dysplasia in 81 patients, close margins for SCC in 5, positive margins for mild epithelial dysplasia in 6, and a positive margin for SCC in one. Those with a positive or a close margin for SCC underwent additional resection 2-4 weeks after surgery; one was proved histologically to have residual SCC. No patients developed local recurrence, but 2 died of neck metastasis and 2 of distant metastasis. The 5-year disease specific survival rate was 93.8%. Lugol's staining during surgery can reduce local recurrence and improve survival in patients with early tongue SCC. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  1. The CRC 20 years: An overview of some of the major achievements and remaining challenges.

    Science.gov (United States)

    Doek, Jaap E

    2009-11-01

    On 20 November 1989, the General Assembly of the United Nations adopted the Convention on the Rights of the Child (CRC). It entered into force on 2 September 1990 and has by now been ratified by 193 States, making the most universally ratified human rights treaty. This overview will present and discuss the impact of this treaty both at the international and the national level, an overview which necessarily has to be limited to some of the developments as a result of the implementation of the CRC. The first part of this paper will be devoted to the impact the CRC had and still has on the setting and development of the international agenda for the promotion and protection of the rights and welfare of children. Special attention will given to developments, achievements, and remaining challenges at the international level with regard to protection of children in armed conflict; prevention and the protection of children from sexual exploitation; and from all forms of violence. This will include some information on the impact of these international developments and actions at the national level, for example, in the area of legislation. The second part will focus on the impact at the national level. Given the wide scope of the CRC this part will be limited to some of the General Measures of Implementation (law reform, national programmes, and independent monitoring) and the General Principles (non-discrimination, best interest, right to be heard) of the CRC. This will be based on reports of States on the implementation of the CRC submitted to the CRC Committee and the Concluding Observations of this Committee and on a number of studies. The conclusion will provide remarks on poverty as one of the major remaining challenges for the implementation of children's rights.

  2. Methods for forming thin-film heterojunction solar cells from I-III-VI[sub 2

    Science.gov (United States)

    Mickelsen, R.A.; Chen, W.S.

    1982-06-15

    An improved thin-film, large area solar cell, and methods for forming the same are disclosed, having a relatively high light-to-electrical energy conversion efficiency and characterized in that the cell comprises a p-n type heterojunction formed of: (1) a first semiconductor layer comprising a photovoltaic active material selected from the class of I-III-VI[sub 2] chalcopyrite ternary materials which is vacuum deposited in a thin composition-graded'' layer ranging from on the order of about 2.5 microns to about 5.0 microns ([approx equal]2.5[mu]m to [approx equal]5.0[mu]m) and wherein the lower region of the photovoltaic active material preferably comprises a low resistivity region of p-type semiconductor material having a superimposed region of relatively high resistivity, transient n-type semiconductor material defining a transient p-n homojunction; and (2), a second semiconductor layer comprising a low resistivity n-type semiconductor material; wherein interdiffusion (a) between the elemental constituents of the two discrete juxtaposed regions of the first semiconductor layer defining a transient p-n homojunction layer, and (b) between the transient n-type material in the first semiconductor layer and the second n-type semiconductor layer, is allowed.

  3. Methods for forming thin-film heterojunction solar cells from I-III-VI{sub 2}

    Science.gov (United States)

    Mickelsen, R.A.; Chen, W.S.

    1985-08-13

    An improved thin-film, large area solar cell, and methods for forming the same are disclosed, having a relatively high light-to-electrical energy conversion efficiency and characterized in that the cell comprises a p-n type heterojunction formed of: (i) a first semiconductor layer comprising a photovoltaic active material selected from the class of I-III-VI{sub 2} chalcopyrite ternary materials which is vacuum deposited in a thin ``composition-graded`` layer ranging from on the order of about 2.5 microns to about 5.0 microns ({approx_equal}2.5 {mu}m to {approx_equal}5.0 {mu}m) and wherein the lower region of the photovoltaic active material preferably comprises a low resistivity region of p-type semiconductor material having a superimposed region of relatively high resistivity, transient n-type semiconductor material defining a transient p-n homojunction; and (ii) a second semiconductor layer comprising a low resistivity n-type semiconductor material; wherein interdiffusion occurs (a) between the elemental constituents of the two discrete juxtaposed regions of the first semiconductor layer defining a transient p-n homojunction layer, and (b) between the transient n-type material in the first semiconductor layer and the second n-type semiconductor layer. 16 figs.

  4. Methods for forming thin-film heterojunction solar cells from I-III-VI.sub. 2

    Science.gov (United States)

    Mickelsen, Reid A.; Chen, Wen S.

    1985-08-13

    An improved thin-film, large area solar cell, and methods for forming the same, having a relatively high light-to-electrical energy conversion efficiency and characterized in that the cell comprises a p-n type heterojunction formed of: (i) a first semiconductor layer comprising a photovoltaic active material selected from the class of I-III-VI.sub.2 chalcopyrite ternary materials which is vacuum deposited in a thin "composition-graded" layer ranging from on the order ot about 2.5 microns to about 5.0 microns (.congruent.2.5 .mu.m to .congruent.5.0 .mu.m) and wherein the lower region of the photovoltaic active material preferably comprises a low resistivity region of p-type semiconductor material having a superimposed region of relatively high resistivity, transient n-type semiconductor material defining a transient p-n homojunction; and (ii), a second semiconductor layer comprising a low resistivity n-type semiconductor material; wherein interdiffusion (a) between the elemental constituents of the two discrete juxtaposed regions of the first semiconductor layer defining a transient p-n homojunction layer, and (b) between the transient n-type material in the first semiconductor layer and the second n-type semiconductor layer, causes the The Government has rights in this invention pursuant to Contract No. EG-77-C-01-4042, Subcontract No. XJ-9-8021-1 awarded by the U.S. Department of Energy.

  5. Mixed-mode I/III fracture toughness of a ferritic/martensitic stainless steel

    International Nuclear Information System (INIS)

    Li, Huaxin; Jones, R.H.; Gelles, D.S.; Hirth, J.P.

    1993-10-01

    The critical J-integrals of mode I (J IC ), mixed-mode I/III (J MC ), and mode III (J IIIC ) were examined for a ferritic stainless steel (F-82H) at ambient temperature. A determination of J MC was made using modified compact-tension specimens. Different ratios of tension/shear stress were achieved by varying the principal axis of the crack plane between 0 and 55 degrees from the load line. Results showed that J MC and tearing modulus (T M ) values varied with the crack angles and were lower than their mode I and mode III counterparts. Both the minimum J MC and T M values occurred at a crack angle between 40 and 50 degrees, where the load ratio of σ i /σ iii was 1.2 to 0.84. The J min was 240 Kj/M 2 , and ratios of J IC /J min and J IIIC /J min were 2.1 and 1.9, respectively. The morphology of fracture surfaces was consistent with the change of J MC and T M values. While the upper shelf-fracture toughness of F-82H depends on loading mode, the J min remains very high. Other important considerations include the effect of mixed-mode loading on the DBT temperature, and effects of hydrogen and irradiation on J min

  6. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases

    Science.gov (United States)

    Schwartz, Daniella M.; Bonelli, Michael; Gadina, Massimo; O’Shea, John J.

    2015-01-01

    Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies—including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs block the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease. PMID:26633291

  7. Fractographic study of epoxy fractured under mode I loading and mixed mode I/III loading

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Fei [ORNL; Wang, Jy-An John [ORNL; Bertelsen, Williams D. [Gougeon Brothers, Inc.

    2011-01-01

    Fiber reinforced polymeric composite materials are widely used in structural components such as wind turbine blades, which are typically subject to complicated loading conditions. Thus, material response under mixed mode loading is of great significance to the reliability of these structures. Epoxy is a thermosetting polymer that is currently used in manufacturing wind turbine blades. The fracture behavior of epoxy is relevant to the mechanical integrity of the wind turbine composite materials. In this study, a novel fracture testing methodology, the spiral notch torsion test (SNTT), was applied to study the fracture behavior of an epoxy material. SNTT samples were tested using either monotonic loading or cyclic loading, while both mode I and mixed mode I/III loading conditions were used. Fractographic examination indicated the epoxy samples included in this study were prone to mode I failure even when the samples were subject to mixed mode loading. Different fatigue precracks were observed on mode I and mixed mode samples, i.e. precracks appeared as a uniform band under mode I loading, and a semi-ellipse under mixed mode loading. Fracture toughness was also estimated using quantitative fractography.

  8. Concurrent chemoradiotherapy in locally advanced carcinoma of the uterine cervix: a phase I/II prospective study

    International Nuclear Information System (INIS)

    Kang, One Chul; Choi, Eun Kyung; Chung, Weon Kuu; Kim, Jong Hoon; Chang, Hye Sook; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun; Mok, Jung Eun; Lee, Moo Song

    1998-01-01

    Prospective, single arm. Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. From May 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The international Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4, 140-5, 040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/m 2 /day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/m 2 /dy intravenous bolus for 3 days, day 1-3, 29-31) administered starting on day 1 of 1 of RT. The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52% and 64%, respectively. The 5-year actuarial survival for stage IIB and II+IVA patients were 58% and 36%, respectively. The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71% and 46%, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9% (19/68): local failure in 5.9% (4/68), distant metastasis in 10.3% (7/68) and both in 11.8% (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment, the complete response rate was 78% (50/64). Concurrent chemoradiation appear to be a

  9. Clinical phase I/II research on ultrasound thermo-chemotherapy in oral and maxillofacial-head and neck carcinoma

    Science.gov (United States)

    Shen, Guofeng; Ren, Guoxin; Guo, Wei; Chen, Yazhu

    2012-11-01

    The principle of a ultrasound thermo-chemotherapy instrument and the clinical phase I/II research on short-term and long-term therapeutic effect and main side-effect of ultrasound hyperthermia combined with chemotherapy in oral and maxillofacial-head & neck carcinoma by the instrument will be presented in this paper.

  10. Identification of sodium channel isoforms that mediate action potential firing in lamina I/II spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Smith Paula L

    2011-09-01

    Full Text Available Abstract Background Voltage-gated sodium channels play key roles in acute and chronic pain processing. The molecular, biophysical, and pharmacological properties of sodium channel currents have been extensively studied for peripheral nociceptors while the properties of sodium channel currents in dorsal horn spinal cord neurons remain incompletely understood. Thus far, investigations into the roles of sodium channel function in nociceptive signaling have primarily focused on recombinant channels or peripheral nociceptors. Here, we utilize recordings from lamina I/II neurons withdrawn from the surface of spinal cord slices to systematically determine the functional properties of sodium channels expressed within the superficial dorsal horn. Results Sodium channel currents within lamina I/II neurons exhibited relatively hyperpolarized voltage-dependent properties and fast kinetics of both inactivation and recovery from inactivation, enabling small changes in neuronal membrane potentials to have large effects on intrinsic excitability. By combining biophysical and pharmacological channel properties with quantitative real-time PCR results, we demonstrate that functional sodium channel currents within lamina I/II neurons are predominantly composed of the NaV1.2 and NaV1.3 isoforms. Conclusions Overall, lamina I/II neurons express a unique combination of functional sodium channels that are highly divergent from the sodium channel isoforms found within peripheral nociceptors, creating potentially complementary or distinct ion channel targets for future pain therapeutics.

  11. 40 CFR 147.1801 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... Injection Control Program—Attorney General's Statement,” July 25, 1984. (e) The Program Description and any..., III, IV and V wells. 147.1801 Section 147.1801 Protection of Environment ENVIRONMENTAL PROTECTION... CONTROL PROGRAMS Ohio § 147.1801 State-administered program—Class I, III, IV and V wells. The UIC program...

  12. 40 CFR 147.1301 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ..., III, IV, and V wells. 147.1301 Section 147.1301 Protection of Environment ENVIRONMENTAL PROTECTION... CONTROL PROGRAMS Missouri § 147.1301 State-administered program—Class I, III, IV, and V wells. The UIC... Administrator on October 10, 1984. (d) Statement of Legal Authority. Opinion No. 123-84, signed by Attorney...

  13. 40 CFR 147.1250 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... Control, State Underground Injection Control (UIC) Program; Statement of the Attorney General of the State..., III, IV, and V wells. 147.1250 Section 147.1250 Protection of Environment ENVIRONMENTAL PROTECTION... CONTROL PROGRAMS Mississippi § 147.1250 State-administered program—Class I, III, IV, and V wells. The UIC...

  14. Molecular epidemiology of Types I/III strains of Mycobacterium avium subspecies paratuberculosis isolated from goats and cattle.

    Science.gov (United States)

    de Juan, L; Alvarez, J; Aranaz, A; Rodríguez, A; Romero, B; Bezos, J; Mateos, A; Domínguez, L

    2006-06-15

    Molecular characterization of Mycobacterium avium subsp. paratuberculosis (M. a. paratuberculosis) isolates classifies them into three groups: cattle or Type II, sheep or Type I, and intermediate or Type III. To avoid problems associated with characterization of extremely slow growth strains, PCR-based techniques that divide the M. a. paratuberculosis strains in two main groups (cattle or Type II, and sheep or Types I/III) can be performed. The objectives of this study were to characterize the M. a. paratuberculosis isolates identified by different PCR-based tests (IS1311-PCR and restriction endonuclease analysis, PCR test based on a DNA sequence difference, and a PCR aimed at three Type I-specific loci), and to determine the clinical and epidemiological implications of Types I/III M. a. paratuberculosis strains in livestock. One hundred and fifty-eight M. a. paratuberculosis strains from domestic ruminants were analyzed. One hundred and six M. a. paratuberculosis isolates (61 from goats and 45 from cattle) were classified as Type II strains; and 52 (29 from cows, 20 from goats, and three from sheep) were included in the Types I/III. The Types I/III M. a. paratuberculosis strains were associated to Spanish native breeds. The majority of these animals had not been in direct or indirect contact with sheep flocks infected with M. a. paratuberculosis. This fact should be taken into account when implementing paratuberculosis control programs.

  15. Radiation therapy for ocular choroidal neovascularization (phase I/II study): preliminary report

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Ogura, Yuichiro; Ngata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

    1997-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angioid streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well-demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the sub retinal neovascular membranes in CNV. We conducted a Phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Methods and Materials: Between April, 1994 and July, 1995, 36 patients with choroidal neovascularization (34 with ARMD and 2 with angioid streaks) were treated with radiation therapy. Treatment planning was performed using a CT simulator that enables real-time treatment planning from multiple CT slices. The clinical target volume that included the macula and optic disc received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions/2 weeks (last 18 eyes). All eyes were irradiated with a single lateral 6 MV photon beam, angled 10 degrees posteriorly to exclude the ipsilateral lens and the contralateral eye from the radiation field. The ipsilateral lens was irradiated with less than 10% of the total reference dose. The field size averaged 3.0 x 2.5 cm. Records of the 17 eyes with CNV referred to our hospital in 1993, which satisfied the eligibility criteria for this study, were retrospectively analyzed for comparison. Results: There was no significant acute morbidity. All patients were followed regularly by both ophthalmologists and radiation oncologists. Cataract formation after 1 year of the treatment was observed in one patient who had received a dose of 20 Gy. One patient who had received 20 Gy complained of transient dry-eye sensation 2 months after treatment, but this had disappeared spontaneously by the fourth month. The subjective symptoms, visual acuity, and size of the neovascular membrane were evaluated at 6 and 12 months after treatment in each patient. In the group of patients irradiated with 10 Gy and with 20 Gy, respectively, subjective symptoms improved in five and seven eyes, did not change in seven and four eyes, and deteriorated in six and six eyes at 12 months. Although visual acuity was significantly decreased in the control group, the patients in both irradiated groups did not show such a decrease in visual acuity. The size of the neovascular membrane in the control group progressed significantly. However, the patients in the 20 Gy group showed significant regression of the membrane, although those in the 10 Gy group showed no significant change in size. Conclusion: This Phase I/II study including a dose escalation study showed that radiation therapy seems to be useful for CNV. The dose of 20 Gy in 10 fractions was more useful in treating neovascular membranes than the dose of 10 Gy in five fractions. These results have encouraged us to start a multicenter randomized prospective study of the treatment of CNV with radiation therapy

  16. Efficient Data Integrity Verification Using CRC Based on HDFS in Cloud Storage

    Directory of Open Access Journals (Sweden)

    Xia Yun-Hao

    2017-01-01

    Full Text Available Data integrity verification is becoming a major challenge in cloud storage which can’t be ignored. This paper proposes an optimized variant of CRC (Checker Redundancy Cyclic verification algorithm based on HDFS to improve the efficiency of data integrity verification in cloud storage through the research of CRC checksum algorithm and data integrity verification mechanism of HDFS. A new method is formulated to establish the deformational optimization and to accelerate the algorithm by researching characteristics of generating and checking the algorithm. Moreover, this method optimizes the code to improve the computational efficiency according to data integrity verification mechanism of HDFS. A data integrity verification system based on Hadoop is designed to verify proposed method. Experimental results demonstrate that proposed HDFS based CRC algorithm was able to improve the calculation efficiency and the utilization of system resource on the whole and outperformed well compared to existing models in terms of accuracy and time.

  17. Finite element analysis and experimental verification of Polymer reinforced CRC improved for close-in detonation

    DEFF Research Database (Denmark)

    Riisgaard, Benjamin; Georgakis, Christos; Stang, Henrik

    2007-01-01

    Compact Reinforced Composite, CRC, is a high-strength cement-based composite that holds an enormous flexural and energy-absorbing capacity due to the close-spaced high strength steel reinforcement and a high-strength cement-based fiber DSP matrix. The material has been used in various constructions...... with the information and data needed to formulate a simple material model for High-Strength Fiber-Reinforced Concrete suitable for predicting the responses of Polymer reinforced CRC under close-in detonations using the general purpose transient dynamic finite element program LS-DYNA....

  18. Conformal prostate brachytherapy: initial experience of a phase I/II dose-escalating trial

    International Nuclear Information System (INIS)

    Martinez, Alvaro; Gonzalez, Jose; Stromberg, Jannifer; Edmundson, Gregory; Plunkett, Marianne; Gustafson, Gary; Brown, Debora; Di, Yan; Vicini, Frank; Brabbins, Donald

    1995-01-01

    Purpose: To improve treatment results on prostatic adenocarcinoma, conformal radiation therapy (CRT) has been used. Two major drawbacks of external CRT are: (a) internal organ motion/daily set-up variations, and (b) exclusion of several patients for CRT based on poor geometrical relationships as identified by three dimensional (3D) treatment planning. To overcome the above problems, we began the first prospective Phase I/II dose-escalating clinical trial of conformal brachytherapy (CB) and concurrent external beam irradiation. Methods and Materials: Fifty-nine patients with T2b-T3c prostatic adenocarcinoma received 176 transperineal ultrasound-guided conformal high-dose rate (HDR) boost implants. All patients received concomitant external beam pelvic irradiation. Dose escalation of the three HDR-CB fractions proceeded as follows: 5.5 Gy (30 patients), 6 Gy (20 patients), and 6.5 Gy (9 patients). The CB dose was prescribed to the prostate contour as outlined using an online biplanar transrectal ultrasound probe. The urethra, anterior rectal wall, and prostate boundaries were identified individually and outlined at 5 mm intervals from the base to the apex of the gland. The CB using real-time ultrasound guidance with interactive online isodose distributions was performed on an outpatient basis. As needles were placed into the prostate, corrections for prostate displacement were recorded and the isodose distributions were recalculated to represent the new relationship between the needles, prostate, and normal structures. No computerized tomography (CT) planning or implant preplanning was required. Results: No patient was rejected based on poor geometrical relation of pelvic structures. In every implant performed, prostate displacement was noted. Craniocaudal motion of the gland ranged from 0.5-2.0 cm (mean = 1.0 cm), whereas lateral displacement was 0.1-0.4 cm. With the interactive online planning system, organ motion was immediately detected, accounted for, and corrected prior to each HDR treatment. The rectal dose has ranged from 45 to 87%, and the urethral dose from 97 to 112% of the prostate dose. It is significant to note that operator dependence has been completely removed because the interactive online planning system uniformly guides the physicians. Conclusions: With ultrasound guidance and the interactive online dosimetry system, organ motion (as compared to external beam) is insignificant because it can be corrected during the procedure without increasing target volume margins. Common pitfalls of brachytherapy, including operator dependence and difficulty with reproducibility, have been eliminated with the intraoperative online planning system

  19. 12 CFR 617.7305 - What is a CRC and who are the members?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is a CRC and who are the members? 617.7305 Section 617.7305 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM BORROWER RIGHTS Actions... least one of the qualified lender's farmer-elected board members. The loan officer involved in the...

  20. Radiation therapy for ocular choroidal neovascularization (phase I/II study)

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Hiraoka, Masahiro

    1996-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angio-streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the subretinal neovascular membranes in CNV. We conducted a phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Materials and Methods: Between April 1994 and July 1995, 36 patients with choroidal neovascularization (34 with ARMD; 2 with angiostreaks) were treated with radiation therapy. Eligibility criteria for this study were as follows: the eyes had subretinal neovascular membranes in the avascular area of the fovea; the neovascular membranes had grown in size in the last 6 months; the best pretreatment corrected visual acuity was worse than (20(25)); there were no large subretinal hemorrhages causing decrease in visual acuity; patients were 50 years or older and had not received laser photocoagulation nor other treatment for this condition. Written informed consent was obtained from all patients. The patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Fluorescein angiography, measurement of the best corrected visual acuity, ophthalmoscopic and biomicroscopic examinations were performed at 1, 3, 6, and 12 months after treatment. Treatment planning was performed using a CT simulator which enables real-time treatment planning from multiple CT slices. The clinical target volume included the macula and optic disc, which received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions/2 weeks (last 18 eyes). All eyes were irradiated with a single lateral 6 MV photon beam, angled 10 degree posteriorly to exclude the ipsilateral lens and the contralateral eye from the radiation field. The ipsilateral lens was irradiated with less than 10% of the total reference dose. The field size averaged 3.0 x 2.5 cm. Records of the 17 eyes with CNV referred to our hospital in 1993, which satisfied the eligibility criteria for this study, were retrospectively analyzed for comparison. Results: There was no significant acute morbidity. All patients were followed regularly by both ophthalmologists and radiation oncologists. One patient treated with a dose of 20 Gy died due to intercurrent disease 2 months after irradiation. Median follow up periods for the group of patients receiving 10 Gy and for the group of patients receiving 20 Gy were 18 months, and 9 months, respectively. One patient who received 20 Gy complained of transient dry-eye sensation 2 months after treatment, but this disappeared spontaneously at the 4th month. Subjective symptoms, visual acuity and size of the neovascular membrane were evaluated 6 months after treatment in each group. In the group of patients irradiated with 10 Gy, subjective symptoms improved in 3 eyes, did not change in 10, and deteriorated in 5. In the 20 Gy group, 8 improved, 5 did not change, and 4 deteriorated. Although visual acuity was significantly decreased in the control group, patients of both irradiated groups did not show such a decrease in visual acuity. The size of the neovascular membrane in the control group progressed significantly. However, patients in the 20 Gy group showed significant regression of the membrane, although the 10 Gy group showed no significant change in size. Conclusions: This phase I/II study including a dose escalation study showed that radiation therapy seems to be useful for CNV. The dose of 20 Gy in 10 fractions was more useful in treating neovascular membranes than the dose of 10 Gy in 5 fractions. These results have encouraged us to start a multi-center randomized prospective study of the treatment of CNV with radiation therapy

  1. Organic Iodine(I, III, and V Chemistry: 10 Years of Development at the Medical University of Warsaw, Poland

    Directory of Open Access Journals (Sweden)

    Lech Skulski

    2000-12-01

    Full Text Available This review reports some novel (or considerably improved methods for the synthesis of aromatic iodides, (dichloroiodoarenes, (diacetoxyiodoarenes, iodylarenes and diaryliodonium salts, as well as some facile, oxidative anion metatheses in crude diaryliodonium halides and, for comparison, potassium halides. All these new results were obtained in our laboratory over the past decade (1990-2000. A full list of our papers dealing with the organic iodine(I, III and V chemistry, covering exlusively the aromatic derivatives, is also provided.

  2. Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers

    Science.gov (United States)

    2017-06-13

    Colorectal Cancer; Gastric Adenocarcinoma; Esophageal Cancer; Hepatocellular Carcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Ovarian Epithelial Cancer; Carcinoma Breast Stage IV; Hormone-refractory Prostate Cancer; Pancreatic Ductal Adenocarcinoma; Head and Neck Cancers- Squamous Cell; Renal Cell Cancer; Urinary Bladder Neoplasms; Cervical Cancer; Endometrial Cancer; Follicular Thyroid Cancer; Glioblastoma Multiforme; Triple Negative Breast Cancer

  3. Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial

    OpenAIRE

    I. L. G. Farias; M. C. S. Araújo; J. G. Farias; L. V. Rossato; L. I. Elsenbach; S. L. Dalmora; N. M. P. Flores; M. Durigon; I. B. M. Cruz; V. M. Morsch; M. R. C. Schetinger

    2012-01-01

    To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects of chemotherapy and improving the antioxidant status of colorectal cancer (CRC) patients, a randomized clinical trial was conducted. Patients (43) undergoing adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin (FOLFOX4) were split into two groups: the UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as a control. Bloo...

  4. Self reported awareness of child maltreatment among school professionals in Saudi Arabia: impact of CRC ratification.

    Science.gov (United States)

    AlBuhairan, Fadia S; Inam, Sarah S; AlEissa, Majid A; Noor, Ismail K; Almuneef, Maha A

    2011-12-01

    The Convention on the Rights of the Child (CRC) was ratified by Saudi Arabia 15 years ago; yet addressing the issue of child maltreatment only began in more recent years. School professionals play a significant role in children's lives, as they spend a great deal of time with them and are hence essential to protecting and identifying those in danger or at risk. The objective of this study is to identify school professional's awareness of child maltreatment and the existing national policies and procedures to examine the extent of efforts made in Saudi Arabia and to activate the roles of schools and school professionals in protecting children from violence and implementation of Article 19 of the CRC. This was a cross-sectional study, where school professionals from randomly selected schools throughout the country were invited to participate in a self-administered questionnaire. A total of 3,777 school professionals participated in the study. Fifty-five percent of professionals had at least 10 years of work experience. A low-level of awareness of child maltreatment was found in about 1/3 of school professionals. Only 1.9% of school professionals had ever attended any sort of specific training on child maltreatment, though 69.3% of those who had not, were willing to attend future training. With regards to awareness of CRC Article 19 or policies and procedures addressing child maltreatment, only 22% reported being aware of it. The majority of school professionals in Saudi Arabia have a low-intermediate level of awareness of child maltreatment, ratification of CRC, and related national policies and procedures, yet most are willing to attend training programs on this subject matter. Efforts need to be made in the country to fill this gap. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Low Complexity List Decoding for Polar Codes with Multiple CRC Codes

    Directory of Open Access Journals (Sweden)

    Jong-Hwan Kim

    2017-04-01

    Full Text Available Polar codes are the first family of error correcting codes that provably achieve the capacity of symmetric binary-input discrete memoryless channels with low complexity. Since the development of polar codes, there have been many studies to improve their finite-length performance. As a result, polar codes are now adopted as a channel code for the control channel of 5G new radio of the 3rd generation partnership project. However, the decoder implementation is one of the big practical problems and low complexity decoding has been studied. This paper addresses a low complexity successive cancellation list decoding for polar codes utilizing multiple cyclic redundancy check (CRC codes. While some research uses multiple CRC codes to reduce memory and time complexity, we consider the operational complexity of decoding, and reduce it by optimizing CRC positions in combination with a modified decoding operation. Resultingly, the proposed scheme obtains not only complexity reduction from early stopping of decoding, but also additional reduction from the reduced number of decoding paths.

  6. Assessing Religious Orientations: Replication and Validation of the Commitment-Reflectivity Circumplex (CRC Model

    Directory of Open Access Journals (Sweden)

    Steven L. Isaak

    2017-09-01

    Full Text Available The Commitment-Reflectivity Circumplex (CRC model is a structural model of religious orientation that was designed to help organize and clarify measurement of foundational aspect of religiousness. The current study successfully replicated the CRC model using multidimensional scaling, and further evaluated the reliability, structure, and validity of their measures in both a university student sample (Study 1 and a nationally representative sample (Study 2. All 10 subscales of the Circumplex Religious Orientation Inventory (CROI demonstrated good reliability across both samples. A two-week test-retest of the CROI showed that the subscales are stable over time. A confirmatory factor analysis of the CROI in the representative adult sample demonstrated good model fit. Finally, the CROI’s validity was examined in relation to the Intrinsic, Extrinsic and Quest measures. Overall, the CROI appears to clarify much of the ambiguity inherent in the established scales by breaking down what were very broad orientations into very specific suborientations. The results suggest that the CRC model is applicable for diverse populations of adults. In addition, the CROI appears to be construct valid with good structural and psychometric properties across all 10 subscales.

  7. Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Watanabe Masahiko

    2011-05-01

    Full Text Available Abstract Background Inhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY, neuronal nitric oxide synthase (nNOS or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III. Results Galanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted ~7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in ~6% of GABAergic boutons in laminae I-IIo, and ~1% of those in laminae IIi-III. Conclusions These results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina II.

  8. Novel Easy Preparations of Some Aromatic Iodine(I, III, and V Reagents, Widely Applied in Modern Organic Synthesis

    Directory of Open Access Journals (Sweden)

    Lech Skulski

    2003-01-01

    Full Text Available We report our novel (or considerably improved methods for the synthesis of aromatic iodides, (dichloroiodoarenes, (diacetoxyiodoarenes, [bis(trifluoroacetoxy-iodo]arenes, iodylarenes and diaryliodonium salts, as well as some facile, oxidative anion metatheses in crude diaryliodonium or tetraalkylammonium halides and, for comparison, potassium halides. All our formerly published papers were discussed and explained in our review “Organic Iodine(I, III, and V Chemistry: 10 Years of Development at the Medical University of Warsaw, Poland” (1990-2000 [1]. Our newest results are discussed below.

  9. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

    Science.gov (United States)

    Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

    2016-04-01

    Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

  10. Phase I-II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints.

    Science.gov (United States)

    Winqvist, Maria; Mozaffari, Fariba; Palma, Marzia; Eketorp Sylvan, Sandra; Hansson, Lotta; Mellstedt, Håkan; Österborg, Anders; Lundin, Jeanette

    2017-01-01

    This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3-4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67 + ) CD8 + T cells was increased at week 4, with further increase in both the CD4 + and CD8 + subsets (p cells increased at week 4 as the frequency of effector memory cells increased in the CD8 + subset (p cells decreased in both the CD8 + and CD4 + subsets (p regulatory T cells was reduced (p T cells decreased, and effector memory T cells increased (p T cells increased at 30-week follow-up (p T cells, including increased proliferative activity and cytotoxic potential.

  11. Influence of the Crc regulator on the hierarchical use of carbon sources from a complete medium in Pseudomonas.

    Science.gov (United States)

    La Rosa, Ruggero; Behrends, Volker; Williams, Huw D; Bundy, Jacob G; Rojo, Fernando

    2016-03-01

    The Crc protein, together with the Hfq protein, participates in catabolite repression in pseudomonads, helping to coordinate metabolism. Little is known about how Crc affects the hierarchy of metabolite assimilation from complex mixtures. Using proton Nuclear Magnetic Resonance (NMR) spectroscopy, we carried out comprehensive metabolite profiling of culture supernatants (metabolic footprinting) over the course of growth of both Pseudomonas putida and P. aeruginosa, and compared the wild-type strains with deletion mutants for crc. A complex metabolite consumption hierarchy was observed, which was broadly similar between the two species, although with some important differences, for example in sugar utilization. The order of metabolite utilization changed upon inactivation of the crc gene, but even in the Crc-null strains some compounds were completely consumed before late metabolites were taken up. This suggests the presence of additional regulatory elements that determine the time and order of consumption of compounds. Unexpectedly, the loss of Crc led both species to excrete acetate and pyruvate as a result of unbalanced growth during exponential phase, compounds that were later consumed in stationary phase. This loss of carbon during growth helps to explain the contribution of the Crc/Hfq regulatory system to evolutionary fitness of pseudomonads. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  12. Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

    Science.gov (United States)

    Mohapatra, Shyam S; Batra, Surinder K; Bharadwaj, Srinivas; Bouvet, Michael; Cosman, Bard; Goel, Ajay; Jogunoori, Wilma; Kelley, Michael J; Mishra, Lopa; Mishra, Bibhuti; Mohapatra, Subhra; Patel, Bhaumik; Pisegna, Joseph R; Raufman, Jean-Pierre; Rao, Shuyun; Roy, Hemant; Scheuner, Maren; Singh, Satish; Vidyarthi, Gitanjali; White, Jon

    2018-05-01

    Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.

  13. Changes in histoanatomical distribution of types I, III and V collagen promote adaptative remodeling in posterior tibial tendon rupture

    Directory of Open Access Journals (Sweden)

    Érika Satomi

    2008-01-01

    Full Text Available INTRODUCTION: Posterior tibial tendon dysfunction is a common cause of adult flat foot deformity, and its etiology is unknown. PURPOSE: In this study, we characterized the morphologic pattern and distribution of types I, III and V collagen in posterior tibial tendon dysfunction. METHOD: Tendon samples from patients with and without posterior tibial tendon dysfunction were stained by immunofluorescence using antibodies against types I, III and V collagen. RESULTS: Control samples showed that type V deposited near the vessels only, while surgically obtained specimens displayed type V collagen surrounding other types of collagen fibers in thicker adventitial layers. Type III collagen levels were also increased in pathological specimens. On the other hand, amounts of collagen type I, which represents 95% of the total collagen amount in normal tendon, were decreased in pathological specimens. CONCLUSION: Fibrillogenesis in posterior tibial tendon dysfunction is altered due to higher expression of types III and V collagen and a decreased amount of collagen type I, which renders the originating fibrils structurally less resistant to mechanical forces.

  14. Effects of solid acellular type-I/III collagen biomaterials on in vitro and in vivo chondrogenesis of mesenchymal stem cells.

    Science.gov (United States)

    Gao, Liang; Orth, Patrick; Cucchiarini, Magali; Madry, Henning

    2017-09-01

    Type-I/III collagen membranes are advocated for clinical use in articular cartilage repair as being able of inducing chondrogenesis, a technique termed autologous matrix-induced chondrogenesis (AMIC). Area covered: The current in vitro and translational in vivo evidence for chondrogenic effects of solid acellular type-I/III collagen biomaterials. Expert commentary: In vitro, mesenchymal stem cells (MSCs) adhere to the fibers of the type-I/III collagen membrane. No in vitro study provides evidence that a type-I/III collagen matrix alone may induce chondrogenesis. Few in vitro studies compare the effects of type-I and type-II collagen scaffolds on chondrogenesis. Recent investigations suggest better chondrogenesis with type-II collagen scaffolds. A systematic review of the translational in vivo data identified one long-term study showing that covering of cartilage defects treated by microfracture with a type-I/III collagen membrane significantly enhanced the repair tissue volume compared with microfracture alone. Other in vivo evidence is lacking to suggest either improved histological structure or biomechanical function of the repair tissue. Taken together, there is a paucity of in vitro and preclinical in vivo evidence supporting the concept that solid acellular type-I/III collagen scaffolds may be superior to classical approaches to induce in vitro or in vivo chondrogenesis of MSCs.

  15. Phase I-II study of radiolabeled antibody integrated in the treatment of primary hepatic malignancies

    International Nuclear Information System (INIS)

    Order, S.E.; Klein, J.L.; Ettinger, D.; Alderson, P.; Siegelman, S.; Leichner, P.

    1984-01-01

    Primary intrahepatic malignancies have been demonstrated to contain tumor associated antigens which bind radiolabelled anti-CEA and anti-ferritin antibodies. The present study reports the toxicity and possible therapeutic efficacy of radiolabelled antibodies that were administered at 50 and 100 millicurie doses following combination radiation and chemotherapy. Three of 10 patients who entered into the study completed therapy on schedule and have had remissions of 7, 9, and 18 months; 2 of the 3 patients were alive at 1 and 2 years after treatment. Of 5 patients who were administered radioimmunoglobulin, the singular toxicity was 3 weeks of marrow hypoplasia in one patient who subsequently recovered. The remaining 5 patients were at various stages of protocol treatment prior to immunoglobulin treatment. Eight of the 10 patients have had computer analysis of sequential computerized axial tomography (CAT) scans obtained during the course of therapy and at follow up examination. No major organ toxicity was noted. Clinical remissions were documented by computer analysis of the CAT scans to determine the percent of residual tumor

  16. Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting

    Directory of Open Access Journals (Sweden)

    van der Meijde Jolanda

    2007-08-01

    Full Text Available Abstract Background Fasting has dramatic effects on small intestinal transport function. However, little is known on expression of intestinal transport and phase I/II metabolism genes during fasting and the role the fatty acid-activated transcription factor PPARα may play herein. We therefore investigated the effects of fasting on expression of these genes using Affymetrix GeneChip MOE430A arrays and quantitative RT-PCR. Results After 24 hours of fasting, expression levels of 33 of the 253 analyzed transporter and phase I/II metabolism genes were changed. Upregulated genes were involved in transport of energy-yielding molecules in processes such as glycogenolysis (G6pt1 and mitochondrial and peroxisomal oxidation of fatty acids (Cact, Mrs3/4, Fatp2, Cyp4a10, Cyp4b1. Other induced genes were responsible for the inactivation of the neurotransmitter serotonin (Sert, Sult1d1, Dtd, Papst2, formation of eicosanoids (Cyp2j6, Cyp4a10, Cyp4b1, or for secretion of cholesterol (Abca1 and Abcg8. Cyp3a11, typically known because of its drug metabolizing capacity, was also increased. Fasting had no pronounced effect on expression of phase II metabolic enzymes, except for glutathione S-transferases which were down-regulated. Time course studies revealed that some genes were acutely regulated, whereas expression of other genes was only affected after prolonged fasting. Finally, we identified 8 genes that were PPARα-dependently upregulated upon fasting. Conclusion We have characterized the response to fasting on expression of transporters and phase I/II metabolic enzymes in murine small intestine. Differentially expressed genes are involved in a variety of processes, which functionally can be summarized as a increased oxidation of fat and xenobiotics, b increased cholesterol secretion, c increased susceptibility to electrophilic stressors, and d reduced intestinal motility. This knowledge increases our understanding of gut physiology, and may be of relevance for e.g. pre-surgery regimen of patients.

  17. The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa

    Science.gov (United States)

    Dong, Yi-Hu; Zhang, Xi-Fen; Zhang, Lian-Hui

    2013-01-01

    The opportunistic pathogen Pseudomonas aeruginosa utilizes type III secretion system (T3SS) to translocate effector proteins into eukaryotic host cells that subvert normal host cell functions to the benefit of the pathogen, and results in serious infections. T3SS in P. aeruginosa is controlled by a complex system of regulatory mechanisms and signaling pathways. In this study, we described that Crc, an RNA-binding protein, exerts a positive impact on T3SS in P. aeruginosa, as evidenced by promoter activity assays of several key T3SS genes, transcriptomics, RT-PCR, and immunoblotting in crc mutant. We further demonstrated that the regulatory function of Crc on the T3SS was mediated through the T3SS master regulator ExsA and linked to the Cbr/Crc signaling system. Expression profiling of the crc mutant revealed a downregulation of flagship T3SS genes as well as 16 other genes known to regulate T3SS gene expression in P. aeruginosa. On the basis of these data, we proposed that Crc may exert multifaceted control on the T3SS through various pathways, which may serve to fine-tune this virulence mechanism in response to environmental changes and nutrient sources. PMID:23292701

  18. IRRIGATION PRACTICES IN LONG-TERM SURVIVORS OF COLORECTAL CANCER (CRC) WITH COLOSTOMIES

    Science.gov (United States)

    Grant, Marcia; McMullen, Carmit K.; Altschuler, Andrea; Hornbrook, Mark C.; Herrinton, Lisa J.; Wendel, Christopher S.; Baldwin, Carol M.; Krouse, Robert S.

    2014-01-01

    Creation of a colostomy in colorectal (CRC) cancer patients results in a loss of control over bowel evacuation. The only way to re-establish some control is through irrigation, a procedure that involves instilling fluid into the bowel to allow for gas and fecal output. This article reports on irrigation practices of participants in a large, multi-site, multi-investigator study of health-related quality of life (HR-QOL) in long term CRC survivors. Questions about irrigation practices were identified in open-ended questions within a large HR-QOL survey and in focus groups of men and women with high and low HR-QOL. Descriptive data on survivors were combined with content analysis of irrigation knowledge and practices. Patient education and use of irrigation in the United States has decreased over the years, with no clear identification of why this change in practice has occurred. Those respondents who used irrigation had their surgery longer ago, and spent more time in colostomy care than those that did not irrigate. Reasons for the decrease in colostomy irrigation are unreported and present priorities for needed research. PMID:23022935

  19. Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer.

    Science.gov (United States)

    Han, Jun; Meng, Qingyang; Xi, Qiulei; Zhang, Yongxian; Zhuang, Qiulin; Han, Yusong; Jiang, Yi; Ding, Qiurong; Wu, Guohao

    2016-01-01

    Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.

  20. Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial.

    Science.gov (United States)

    Farias, I L G; Araújo, M C S; Farias, J G; Rossato, L V; Elsenbach, L I; Dalmora, S L; Flores, N M P; Durigon, M; Cruz, I B M; Morsch, V M; Schetinger, M R C

    2012-01-01

    To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects of chemotherapy and improving the antioxidant status of colorectal cancer (CRC) patients, a randomized clinical trial was conducted. Patients (43) undergoing adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin (FOLFOX4) were split into two groups: the UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as a control. Blood samples were collected before each of the 6 cycles of chemotherapy, and hemograms, oxidative stress, enzymes antioxidants, immunologic parameters, and adverse events were analyzed. The use of 300 mg of Uncaria tomentosa daily during 6 cycles of FOLFOX4 did not change the analyzed parameters, and no toxic effects were observed.

  1. Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial

    Directory of Open Access Journals (Sweden)

    I. L. G. Farias

    2012-01-01

    Full Text Available To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects of chemotherapy and improving the antioxidant status of colorectal cancer (CRC patients, a randomized clinical trial was conducted. Patients (43 undergoing adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin (FOLFOX4 were split into two groups: the UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as a control. Blood samples were collected before each of the 6 cycles of chemotherapy, and hemograms, oxidative stress, enzymes antioxidants, immunologic parameters, and adverse events were analyzed. The use of 300 mg of Uncaria tomentosa daily during 6 cycles of FOLFOX4 did not change the analyzed parameters, and no toxic effects were observed.

  2. Final long-term results of a phase I/II study of dose-escalated intensity-modulated radiotherapy for locally advanced laryngo-hypopharyngeal cancers.

    Science.gov (United States)

    Gujral, Dorothy M; Miah, Aisha B; Bodla, Shankar; Richards, Thomas M; Welsh, Liam; Schick, Ulrike; Powell, Ceri J; Clark, Catharine H; Bidmead, Margaret A; Grove, Lorna; Guerrero-Urbano, Teresa; Bhide, Shreerang A; Newbold, Kate L; Harrington, Kevin J; Nutting, Christopher M

    2014-11-01

    We previously described dose-escalated intensity-modulated radiotherapy (IMRT) in squamous cell cancer of the larynx/hypopharynx (SCCL/H) to offer improved locoregional control with a low incidence of toxicity at 2 years. We now present outcome and safety data at 5 years. A sequential cohort Phase I/II trial design was used. Patients with SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Between 09/2002 and 01/2008, 60 patients (29 DL1, 31 DL2) with stage III (41% DL1, 52% DL2) and stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 5.7 (1.0-10.2) years and for DL2 was 6.0 (0.3-8.4) years. Five-year local control rates (95% confidence interval) for DL1 and DL2, respectively, were 68% (50.6-85.4%) and 75% (58.9-91.1%), locoregional progression-free survival rates were 54% (35.6-72.4%) and 62.6% (44.8-80.4%), and overall survival was 61.9% (44.1-79.7) and 67.6 (51.1-84.1%). Five-year laryngeal preservation rates were 66.7% (37.4-87.9%) and 71.4% (44.4-85.8%), respectively. Cumulative toxicities reported were: one patient in DL1 and 2 in DL2 developed benign pharyngeal strictures. No other G3/4 toxicities were reported. Dose-escalated IMRT at DL2 achieves higher 5-year local control, larynx preservation and survival rates with acceptable late toxicity. Recruitment into a Cancer Research UK Phase III study (ART-DECO), with DL2 as the experimental arm, is ongoing. Copyright © 2014. Published by Elsevier Ltd.

  3. Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone

    NARCIS (Netherlands)

    Massard, C.; Mateo, J.; Loriot, Y.; Pezaro, C.; Albiges, L.; Mehra, N.; Varga, A.; Bianchini, D.; Ryan, C.J.; Petrylak, D.P.; Attard, G.; Shen, L.; Fizazi, K.; Bono, J. De

    2017-01-01

    Background: Abiraterone and cabazitaxel improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted an open-label phase I/II trial of cabazitaxel plus abiraterone to assess the antitumor activity and tolerability in patients with progressive mCRPC after

  4. Multinary I-III-VI2 and I2-II-IV-VI4 Semiconductor Nanostructures for Photocatalytic Applications.

    Science.gov (United States)

    Regulacio, Michelle D; Han, Ming-Yong

    2016-03-15

    are the multinary chalcogenide semiconductors (MCSs), which include the ternary I-III-VI2 semiconductors (e.g., AgGaS2, CuInS2, and CuInSe2) and the quaternary I2-II-IV-VI4 semiconductors (e.g., Cu2ZnGeS4, Cu2ZnSnS4, and Ag2ZnSnS4). These inorganic compounds consist of environmentally benign elemental components, exhibit excellent light-harvesting properties, and possess band gap energies that are well-suited for solar photon absorption. Moreover, the band structures of these materials can be conveniently modified through alloying to boost their ability to harvest visible photons. In this Account, we provide a summary of recent research on the use of ternary I-III-VI2 and quaternary I2-II-IV-VI4 semiconductor nanostructures for light-induced photocatalytic applications, with focus on hydrogen production and organic dye degradation. We include a review of the solution-based methods that have been employed to prepare multinary chalcogenide semiconductor nanostructures of varying compositions, sizes, shapes, and crystal structures, which are factors that are known to have significant influence on the photocatalytic activity of semiconductor photocatalysts. The enhancement of photocatalytic performance through creation of hybrid nanoscale architectures is also presented. Lastly, views on the current challenges and future directions are discussed in the concluding section.

  5. Anti-VEGF agents in metastatic colorectal cancer (mCRC: are they all alike?

    Directory of Open Access Journals (Sweden)

    Saif MW

    2013-06-01

    Full Text Available Muhammad Wasif Saif GI Oncology Program, Tufts University School of Medicine, Boston, MA, USA Abstract: Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States, VEGF receptors (eg, ramucirumab, and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors. The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012, using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking. Keywords: aflibercept, antiangiogenesis, metastatic colorectal cancer (mCRC, tyrosine kinase inhibitor (TKI, vascular endothelial growth factor (VEGF

  6. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    International Nuclear Information System (INIS)

    Mimura, Hidefumi; Arai, Yasuaki; Yamakado, Koichiro; Sone, Miyuki; Takeuchi, Yoshito; Miki, Tsuneharu; Gobara, Hideo; Sakuhara, Yusuke; Yamamoto, Takanobu; Sato, Yozo; Kanazawa, Susumu

    2016-01-01

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  7. Phase I/II trial of the anti-HIV activity of mifepristone in HIV-infected subjects ACTG 5200.

    Science.gov (United States)

    Para, Michael F; Schouten, Jeff; Rosenkranz, Susan L; Yu, Song; Weiner, David; Tebas, Pablo; White, C Jo; Reeds, Dominic; Lertora, Juan; Patterson, Kristine B; Daar, Eric S; Cavert, Winston; Brizz, Barbara

    2010-04-01

    Mifepristone is a glucocorticoid receptor inhibitor shown in vitro to have anti-HIV activity and anti-simian immunodeficiency virus activity in a macaque model. A phase I/II trial was performed to assess the drug's safety and anti-HIV activity. A 28-day double-blind, placebo-controlled trial of mifepristone at doses of 75 mg, 150 mg, and 225 mg given daily was conducted in HIV+ persons with CD4+ lymphocyte counts >or=350 cells per cubic millimeter who had no recent antiretroviral therapy. Fifty-six male and 1 female subjects with a median entry CD4+ lymphocyte count of 555 cells per cubic millimeter and plasma HIV-1 RNA of 15,623 copies per milliliter were accrued. Forty-five subjects (78.9%) were available for endpoint analysis. In each arm, changes from baseline to day 28 in plasma HIV-1 RNA and CD4+ lymphocyte count were not significantly different from zero (no change). There was no relationship between mifepristone trough concentrations and plasma HIV-1 RNA. Day 28 morning plasma cortisol levels were significantly higher in the 150 mg and 225 mg arms compared with placebo, confirming biologic activity, and returned to baseline by day 56. Serum lipids did not change during the trial. Fasting blood sugar was 2.5 mg/dL higher on day 28 in the mifepristone arms, but the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) did not change. Three subjects (7.3%) receiving mifepristone developed a grade 2 rash. Mifepristone at doses of 75-225 mg daily was safe and well-tolerated, but did not show significant anti-HIV activity.

  8. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    Energy Technology Data Exchange (ETDEWEB)

    Mimura, Hidefumi, E-mail: mimura@marianna-u.ac.jp [St. Marianna University School of Medicine, Department of Radiology (Japan); Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp [Mie University School of Medicine, Department of Interventional Radiology (Japan); Sone, Miyuki, E-mail: msone@me.com; Takeuchi, Yoshito, E-mail: yotake62@qg8.so-net.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Miki, Tsuneharu, E-mail: tmiki@koto.kpu-m.ac.jp [Kyoto Prefectural University of Medicine, Department of Urology (Japan); Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan); Sakuhara, Yusuke, E-mail: yusaku@med.hokudai.ac.jp [Hokkaido University School of Medicine, Department of Diagnostic and Interventional Radiology (Japan); Yamamoto, Takanobu, E-mail: tyamamot@tcc.pref.tochigi.lg.jp [Tochigi Cancer Center, Department of Radiology (Japan); Sato, Yozo, E-mail: ysato@aichi-cc.jp [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kanazawa, Susumu, E-mail: susumu@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan)

    2016-05-15

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  9. Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Hu Bang

    2012-03-01

    Full Text Available Abstract Background Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5 expression in human colorectal cancer (CRC tissues and correlated it with clinicopathologic data. Methods pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively. Results pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2% than in normal tissues (6 out of 80, 7.5%; P P = 0.001, lymph node metastasis (P P P P P = 0.002 and 5-year overall survival rate (P P = 0.139; OS: P = 0.071. Conclusions pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.

  10. CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

    International Nuclear Information System (INIS)

    Seidel, Claudia; Dietrich, Antje; Wondrak, Marit; Kunz-Schughart, Leoni A.; Grade, Marian; Ried, Thomas

    2009-01-01

    The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133 + ) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133 + subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133 + cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133 + / CD133 - subpopulations

  11. Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer--A preliminary report

    International Nuclear Information System (INIS)

    Teh, Bin S.; Aguilar-Cordova, Estuardo; Kernen, Kenneth; Chou, C.-C.; Shalev, Moshe; Vlachaki, Maria T.; Miles, Brian; Kadmon, Dov; Mai, W.-Y.; Caillouet, James; Davis, Maria; Ayala, Gustavo; Wheeler, Thomas; Brady, Jett; Carpenter, L. Steve; Lu, Hsin H.; Chiu, J. Kam; Woo, Shiao Y.; Thompson, Timothy; Butler, E. Brian

    2001-01-01

    Purpose: To report the preliminary results of a Phase I/II study combining radiotherapy and in situ gene therapy (adenovirus/herpes simplex virus thymidine kinase gene/valacyclovir) with or without hormonal therapy in the treatment of prostate cancer. Methods and Materials: Arm A: low-risk patients (T1-T2a, Gleason score <7, pretreatment PSA <10) were treated with combined radio-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated radiotherapy. Arm B: high-risk patients (T2b-T3, Gleason score ≥7, pretreatment PSA ≥10) were treated with combined radio-gene therapy and hormonal therapy. Hormonal therapy was comprised of a 4-month leuprolide injection and 2-week use of flutamide. Arm C: Stage D1 (positive pelvic lymph node) patients received the same regimen as Arm B, with the additional 45 Gy to the pelvic lymphatics. Treatment-related toxicity was assessed using Cancer Therapy Evaluation Program common toxicity score and Radiation Therapy Oncology Group (RTOG) toxicity score. Results: Thirty patients (13 in Arm A, 14 in Arm B, and 3 in Arm C) completed the trial. Median follow-up was 5.5 months. Eleven patients (37%) developed flu-like symptoms (Cancer Therapy Evaluation Program Grade 1) of fatigue and chills/rigors after gene therapy injection but recovered within 24 h. Four patients (13%) and 2 patients (7%) developed Grade 1 and 2 fever, respectively. There was no patient with weight loss. One patient in Arm B developed Grade 3 elevation in liver enzyme, whereas 11 and 2 patients developed Grade 1 and 2 abnormal liver function tests. There was no Grade 2 or above hematologic toxicity. Three patients had transient rise in creatinine. There was no RTOG Grade 3 or above lower gastrointestinal toxicity. Toxicity levels were as follows: 4 patients (13%), Grade 2; 6 patients (20%), Grade 1; and 20 patients (67%), no toxicity. There was 1 patient with RTOG Grade 3 genitourinary toxicity, 12 patients (40%) with Grade 2, 8 patients

  12. Many unexpected abdominal findings on staging computed tomography in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Holmsted, Kim; Nørring, Keld; Laustrup, Lene Collatz

    2011-01-01

    Computed tomography (CT) was proven to be superior to preoperative abdominal ultrasound in the preoperative setting for detection of hepatic metastases from colorectal cancer (CRC). The higher sensitivity of CT has resulted in a number of unexpected abdominal findings of varying importance......; an issue that was previously studied in relation to CT colonography, but not in relation to staging CT with intravenous contrast in CRC patients. The aim of the present study was to evaluate the number and significance of such unexpected findings on staging CTs in CRC patients....

  13. Many unexpected abdominal findings on staging computed tomography in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Holmsted, Kim; Nørring, Keld; Laustrup, Lene Collatz

    2011-01-01

    ; an issue that was previously studied in relation to CT colonography, but not in relation to staging CT with intravenous contrast in CRC patients. The aim of the present study was to evaluate the number and significance of such unexpected findings on staging CTs in CRC patients.......Computed tomography (CT) was proven to be superior to preoperative abdominal ultrasound in the preoperative setting for detection of hepatic metastases from colorectal cancer (CRC). The higher sensitivity of CT has resulted in a number of unexpected abdominal findings of varying importance...

  14. Phase I/II Study Evaluating Early Tolerance in Breast Cancer Patients Undergoing Accelerated Partial Breast Irradiation Treated With the MammoSite Balloon Breast Brachytherapy Catheter Using a 2-Day Dose Schedule

    International Nuclear Information System (INIS)

    Wallace, Michelle; Martinez, Alvaro; Mitchell, Christina; Chen, Peter Y.; Ghilezan, Mihai; Benitez, Pamela; Brown, Eric; Vicini, Frank

    2010-01-01

    Purpose: Initial Phase I/II results using balloon brachytherapy to deliver accelerated partial breast irradiation (APBI) in 2 days in patients with early-stage breast cancer are presented. Materials and Methods: Between March 2004 and August 2007, 45 patients received adjuvant radiation therapy after lumpectomy with balloon brachytherapy in a Phase I/II trial delivering 2800 cGy in four fractions of 700 cGy. Toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria for Adverse Events v3.0 scale and cosmesis was documented at ≥6 months. Results: The median age was 66 years (range, 48-83) and median skin spacing was 12 mm (range, 8-24). The median follow-up was 11.4 months (5.4-48 months) with 21 patients (47%) followed ≥1 year, 11 (24%) ≥2 years, and 7 (16%) ≥3 years. At <6 months (n = 45), Grade II toxicity rates were 9% radiation dermatitis, 13% breast pain, 2% edema, and 2% hyperpigmentation. Grade III breast pain was reported in 13% (n = 6). At ≥6 months (n = 43), Grade II toxicity rates were: 2% radiation dermatitis, 2% induration, and 2% hypopigmentation. Grade III breast pain was reported in 2%. Infection was 13% (n = 6) at <6 months and 5% (n = 2) at ≥6 months. Persistent seroma ≥6 months was 30% (n = 13). Fat necrosis developed in 4 cases (2 symptomatic). Rib fractures were seen in 4% (n = 2). Cosmesis was good/excellent in 96% of cases. Conclusions: Treatment with balloon brachytherapy using a 2-day dose schedule resulted acceptable rates of Grade II/III chronic toxicity rates and similar cosmetic results observed with a standard 5-day accelerated partial breast irradiation schedule.

  15. Identification of gene expression changes from colitis to CRC in the mouse CAC model.

    Directory of Open Access Journals (Sweden)

    Xin Li

    Full Text Available A connection between colorectal carcinogenesis and inflammation is well known, but the underlying molecular mechanisms have not been elucidated. Chemically induced colitis-associated cancer (CAC is an outstanding mouse model for studying the link between inflammation and cancer. Additionally, the CAC model is used for examining novel diagnostic, prognostic, and predictive markers for use in clinical practice. Here, a CAC model was established in less than 100 days using azoxymethane (AOM with dextran sulfate sodium salt (DSS in BALB/c mice. We examined the mRNA expression profiles of three groups: control untreated mice (K, DSS-induced chronic colitis mice (D, and AOM/DSS-induced CAC (AD mice. We identified 6301 differentially expressed genes (DEGs among the three groups, including 93 persistently upregulated genes and 139 persistently downregulated genes. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway analyses revealed that the most persistent DEGs were significantly enriched in metabolic or inflammatory components in the tumor microenvironment. Furthermore, several associated DEGs were identified as potential DEGs by protein-protein interaction (PPI network analysis. We selected 14 key genes from the DEGs and potential DEGs for further quantitative real-time PCR (qPCR verification. Six persistently upregulated, 3 persistently downregulated DEGs, and the other 3 genes showed results consistent with the microarray data. We demonstrated the regulation of 12 key genes specifically involved in Wnt signaling, cytokine and cytokine receptor interactions, homeostasis, and tumor-associated metabolism during colitis-associated CRC. Our results suggest that a close relationship between metabolic and inflammatory mediators of the tumor microenvironment is present in CAC.

  16. Calibration of the Capintec CRC-712M dose calibrator for 18F

    International Nuclear Information System (INIS)

    Mo, L.; Reinhard, M.I.; Davies, J.B.; Alexiev, D.; Baldock, C.

    2006-01-01

    Primary standardisation was performed on a solution of 18 F using the 4πβ-γ coincidence counting efficiency-tracing extrapolation method with 60 Co used as a tracer nuclide. The result was used to calibrate the ANSTO secondary standard ionisation chamber which is used to disseminate Australian activity standards for gamma emitters. Using the secondary activity standard for 18 F, the Capintec CRC-712M dose calibrator at the Australian National Medical Cyclotron (NMC) Positron Emission Tomography (PET) Quality Control (QC) Section was calibrated. The dial setting number recommended by the manufacturer for the measurement of the activity of 18 F is 439. In this work, the dial setting numbers for the activity measurement of the solution of 18 F in Wheaton vials were experimentally determined to be 443+/-12, 446+/-12, 459+/-11, 473+/-15 for 0.1, 1, 4.5 and 9ml solution volumes, respectively. The uncertainties given above are expanded uncertainties (k=2) giving an estimated level of confidence of 95%. The activities determined using the manufacturer recommended setting number 439 are 0.8%, 1.4%, 4.0% and 6.5% higher than the standardised activities, respectively. It is recommended that a single dial setting number of 459 determined for 4.5ml is used for 0.1-9ml solution in Wheaton vials in order to simplify the operation procedure. With this setting the expended uncertainty (k=2) in the activity readout from the Capintec dose calibrator would be less than 6.2%

  17. The Practicability of a Novel Prognostic Index (PI) Model and Comparison with Nottingham Prognostic Index (NPI) in Stage I-III Breast Cancer Patients Undergoing Surgical Treatment.

    Science.gov (United States)

    Wen, Jiahuai; Ye, Feng; Li, Shuaijie; Huang, Xiaojia; Yang, Lu; Xiao, Xiangsheng; Xie, Xiaoming

    2015-01-01

    Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI) model for breast cancer patients based on the potential prognostic factors. A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model) was performed to determine the independent prognostic factors and a prognostic index (PI) model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI) by evaluating the area under the receiver operating characteristics curves (AUC). The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%), moderate- (410 patients, 24.7%) and high-risk groups (83 patients, 5.0%), respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR): 1.513, 95% confidence interval (CI): 1.169-1.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.653-3.724, p< 0.001). The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients.

  18. Circulating tyrosinase and MART-1 mRNA does not independently predict relapse or survival in patients with AJCC stage I-II melanoma

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Sørensen, Boe Sandahl; Sjøgren, Pia

    2006-01-01

    The detection of melanoma cells in peripheral blood has been proposed to       select patients with a high risk of relapse. In this study, tyrosinase and       melanoma antigen recognized by T cells 1 (MART-1) mRNA expression was       evaluated in serial samples obtained before definitive surgery...... tumor site,       ulceration, thickness, Clark level, and histological subtype were analyzed       together with tyrosinase and MART-1 mRNA treated as updated covariates in       a Cox proportional-hazard model. After a median follow-up time of 66       months, 42 out of 236 patients (18%) had relapsed....... The following variables       were significantly associated with relapse-free survival in the univariate       analyses: tyrosinase, MART-1, gender, ulceration, thickness, Clark level,       and histological subtype. Entering these covariates into a multivariate       Cox analysis resulted in thickness...

  19. Safety and Tolerability of Empagliflozin in Patients with Type 2 Diabetes: Pooled Analysis of Phase I-III Clinical Trials.

    Science.gov (United States)

    Kohler, Sven; Zeller, Cordula; Iliev, Hristo; Kaspers, Stefan

    2017-07-01

    We characterized the safety and tolerability of empagliflozin in patients with type 2 diabetes (T2DM) randomized 1:1:1 to placebo, empagliflozin 10 mg, or empagliflozin 25 mg in clinical trials. Pooled data were analyzed from patients with T2DM treated with placebo (N = 4203), empagliflozin 10 mg (N = 4221), or empagliflozin 25 mg (N = 4196) in 15 randomized phase I-III trials plus four extension studies. Adverse events (AEs) were assessed descriptively in participants who took at least one dose of study drug. AE incidence rates per 100 patient-years were calculated to adjust for differences in drug exposure between trials. Total exposure was 7369, 7782, and 7754 patient-years in the placebo, empagliflozin 10 mg, and 25 mg groups, respectively. The incidence of any AEs, severe AEs, serious AEs, and AEs leading to discontinuation was no higher in participants treated with empagliflozin vs. placebo. Empagliflozin was not associated with an increased risk of hypoglycemia vs. placebo, except in participants on background sulfonylurea. The incidence of events consistent with urinary tract infection was similar across treatment groups (8.7-9.5/100 patient-years). Events consistent with genital infection occurred more frequently in participants treated with empagliflozin 10 and 25 mg (3.5 and 3.4/100 patient-years, respectively) than placebo (0.9/100 patient-years). The incidence of AEs consistent with volume depletion was similar across treatment groups (1.7-1.9/100 patient-years) but was higher with empagliflozin 10 mg and 25 mg vs. placebo in participants aged 75 years or older (3.2 and 3.0 vs. 2.3/100 patient-years, respectively). The rates of bone fractures, cancer events, renal AEs, venous thromboembolic events, hepatic injury, acute pancreatitis, lower limb amputations, and diabetic ketoacidosis were similar across treatment groups. This analysis of pooled safety data based on more than 15,000 patient-years' exposure supports a favorable

  20. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE: the IEO phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M.; Baio, Silvia M.; Lombardo, Dario; Chinol, Marco; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta; Ferrari, Mahila E. [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Fazio, Nicola [European Institute of Oncology, Division of Medical Oncology, Milan (Italy); Iodice, Simona [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Bartolomei, Mirco [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); M. Bufalini Hospital, Division of Nuclear Medicine, Cesena, FC (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Unit of Radiometabolic Medicine, Meldola, FC (Italy)

    2011-12-15

    Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst{sub 2}), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of {sup 177}Lu-DOTATATE in multiple cycles. Fifty-one consecutive patients with unresectable/metastatic sst{sub 2}-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of {sup 177}Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. {sup 177}Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. (orig.)

  1. Phase I/II trial of simultaneous whole-brain irradiation and dose-escalating topotecan for brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Kocher, M.; Eich, H.T.; Semrau, R.; Guener, S.A.; Mueller, R.P. [Dept. of Radiation Oncology, Univ. Hospital, Univ. of Cologne, Cologne (Germany)

    2005-01-01

    Background and purpose: topotecan penetrates the blood-brain barrier and sensitizes tumor cells against radiation. A phase I/II dose-escalating trial of repetitive daily i.v. topotecan application simultaneously with whole-brain irradiation (WBRT) was conducted to estimate toxicity, maximum tolerated dose and survival in patients with inoperable brain metastases. Patients and methods: in 47 patients suffering from previously untreated brain metastases, topotecan was applied on a daily i.v. schedule simultaneously with WBRT (36 Gy/3-Gy fractions). The infusion schedule started at the beginning of WBRT and was discontinued during weekends. Each infusion was completed within 1-2 h before irradiation. In a dose-finding study, topotecan was escalated from 5 x 0.5 mg/m{sup 2}, 8 x 0.5 mg/m{sup 2}, 12 x 0.5 mg/m{sup 2} to 12 x 0.6 mg/m{sup 2}. Results: altogether, 38/47 patients (81%) completed the prescribed schedule. Leukopenia and thrombocytopenia were dose-limiting. Grade 3/4 hematologic toxicity occurred in 5/32 chemonaive patients (16%) and 7/15 patients (47%) with previous chemotherapy. At 12 x 0.6 mg/m{sup 2}, 2/4 patients experienced grade 4 leukopenia/thrombopenia. Nonhematologic toxicities were generally mild to moderate and unrelated to topotecan. Response evaluation was possible in 26/47 patients, overall response rate was 58% (CR [complete remission] 5/26, PR [partial remission] 10/26, NC [no change] 8/26). Median survival amounted to 5.1 months. In 15/42 patients (36%), brain metastases were the dominant cause of death. Conclusion: for a daily topotecan schedule simultaneous to WBRT, the maximum tolerated dose is 12 x 0.5 mg/m{sup 2} in chemonaive patients. For chemo-pretreated patients, daily doses should be reduced to 0.4 mg/m{sup 2}. A phase III trial has now been started to find out whether WBRT + topotecan increases survival compared to WBRT alone. (orig.)

  2. An overview of the MIZ-1 borehole investigations during phase I/II. MIZ-1 progress report 03-01

    International Nuclear Information System (INIS)

    Ota, Kunio; Takeuchi, Shinji; Ikeda, Koki

    2004-05-01

    Surface-based investigations have now been carried out, in a step-by-step fashion, with the main aims of the development of conceptual models of the geological environment and the enhancement of the understanding of the undisturbed deep geological environment before excavation of the shafts and experimental drifts. The MIZ-1 borehole investigation programme was launched in December 2002, as a step of the field investigations at the MIU Construction Site. The overall goals of the MIZ-1 borehole investigations are to characterise the geological environment from the surface to over 1,000 m depth in the crystalline basement, to establish baseline conditions before excavation of the shafts and experimental drifts, and to provide a deep borehole for observing hydraulic responses during the shaft and drift excavation and experiments in the drifts during the Construction and the Operation Phases. The borehole is planned to be drilled in an overall south-westerly direction from the north-eastern area of the MIU Site. The planned inclination varies from vertical at shallower depths to 12deg from vertical at greater depths down to 1,350 m along the borehole length, which will be achieved by controlled directional drilling. In MIZ-1 Phase I/II (from March to May 2003), the borehole was drilled vertically, through the entire sedimentary formations, down to 123.00 m in the uppermost part of the Toki granite at the MIU Construction Site. The new method of wireline core drilling with a downhole motor was introduced for the drilling. Planned geological, geophysical and hydrochemical investigations and complementary hydraulic and hydrochemical monitoring were performed. In addition, as a complete loss of drilling fluid was encountered at 115.85 m along the borehole length, modified work procedures resulted in the execution of hydraulic tests with groundwater sampling, from necessity, in that section and of further drilling work. The local QC system was applied to all the investigations. Quality-controlled data on geology, hydrogeology and hydrochemistry of the sedimentary formations and the Toki granite were acquired, thereby advancing the understanding of the shallow geological environment at the MIU Construction Site. Specifically, a very highly transmissive WCF and Na-Cl-HCO 3 type groundwater in the uppermost part of the Toki granite were identified. However, the difficulty in modelling heterogeneous geological structures was highlighted. In addition, throughout the investigation programme, from technical and QC viewpoints, a range of successes and set-backs was produced and lessons and feedback from the achievements were obtained. (author)

  3. Motivations to participate in a Phase I/II HIV vaccine trial: A descriptive study from Dar es Salaam, Tanzania

    Directory of Open Access Journals (Sweden)

    E. A. M. Tarimo

    2016-02-01

    Full Text Available Abstract Background The search for an efficacious HIV vaccine is a global priority. To date only one HIV vaccine trial (RV144 has shown modest efficacy in a phase III trial. With existing different HIV-1 subtypes and frequent mutations, multiple trials are needed from different geographical sites particularly in sub-Saharan Africa where most HIV infections occur. Thus, motivations to participate in HIV vaccine trials among Tanzanians need to be assessed. This paper describes the motives of Police Officers who showed great interest to volunteer in HIVIS-03 in Dar es Salaam, Tanzania. Methods A descriptive cross-sectional study was conducted among Police Officers who showed interest to participate in the HIVIS-03, a phase I/II HIV vaccine trial in Dar es Salaam. Prior to detailed training sessions about HIV vaccine trials, the potential participants narrated their individual motives to participate in the trial on a piece of paper. Descriptive analysis using content approach and frequency distributions were performed. Results Of the 265 respondents, 242 (91.3 % provided their socio-demographic characteristics as well as reasons that would make them take part in the proposed trial. Majority, (39.7 %, cited altruism as the main motive. Women were more likely to volunteer due to altruism compared to men (P < 0.01. Researchers’ explanations about HIV/AIDS vaccine studies motivated 15.3 %. More men (19.6 % than women (1.7 % were motivated to volunteer due to researchers’ explanations (P < 0.001. Also, compared to other groups, those unmarried and educated up to secondary level of education were motivated to volunteer due to researchers’ explanation (P < 0.05. Other reasons were: desire to become a role model (18.6 %; to get knowledge for educating others (14.0 %; to cooperate with researchers in developing an HIV vaccine (9.5 %; to get protection against HIV infection (7.0 %, and severity of the disease within families (6.2 %. These results were supported by testimonies from both men and women. Conclusions Participation in an HIV vaccine trial in a Tanzanian context is likely to be influenced by altruism and comprehensive education about the trial. Gender differences, marital status and education level need to be considered to enhance participation in future HIV vaccine trials.

  4. [Clinical reasoning of impact of contemporary partial dentures constructions on the condition of periodontal tissues of patients with generalized periodontitis of I-II severity].

    Science.gov (United States)

    Kochkina, N A

    2014-12-01

    The aim of the study was the evaluation of the effectiveness of using partial dentures made of thermoplastic materials for patients with generalized periodontitis of I-II degree of severity based on the results of clinical research. The effect of partial dentures made of acrylic, metal and thermoplastic materials with and without splinting elements of fixation on the state of periodontal tissues in patients with generalized periodontitis was studied. The results of clinical studies of patients periodontal tissues condition ,who have had dental defects on the background I-II severity of GP using partial splinting elements of fixation showed a significant improvement in oral hygiene, positive change in activity indicators current of generalized periodontitis. The group of patients for whom were made orthopedic constructions of thermoplastic masses, noticed reducing of the depth of periodontal pockets, tooth mobility, bleeding and inflammation of the interdental papillae and the gingival margin.

  5. [Processes of ventricles I-III. Review of the patient population of the Neurosurgery Clinic of the Karl Marx University 1953-1983].

    Science.gov (United States)

    Niebeling, H G; Goldhahn, W E

    1985-01-01

    Within three decades 254 patients with processes of the brain ventricles I-III have been treated at the Leipzig Neurosurgical Clinic. The article subdivides the patients in general and according to the histology, localisation, lateral differences, dignity, operability as well as the postoperative lethality. The evaluation gives many clues with respect to the diagnostics and therapy of these ventricular processes. Today, the improvements obtained by computer tomography and by microsurgery are well the to fore.

  6. Improving the accuracy of derivation of the Williams’ series parameters under mixed (I+II) mode loading by compensation of measurement bias in the stress field components data

    International Nuclear Information System (INIS)

    Lychak, Oleh V; Holyns’kiy, Ivan S

    2016-01-01

    A new method for compensation of bias in the stress field components measurement data used for Williams’ series parameters derivation was presented. Essential increase of accuracy of derivation of SIF-related leading terms in series under mixed (I+II) mode loading was demonstrated. It was shown that a relatively low value of bias in the stress field components data error could result in the essential deviation of the values of derived Williams’ coefficients and the crack tip coordinates. (paper)

  7. Identification of miRNAs associated with recurrence of stage II colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Tobiasen, Heidi; Schepeler, Troels

    2011-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer deaths. Twenty-five percent of the patients radically treated for a stage II CRC (no lymph node or distant metastasis) later develop recurrence and dies from the disease. MicroRNAs (miRNAs) are aberrantly expressed or mutated in human...... cancers, and function either as tumour suppressors or oncogenes. Additionally, they also appear to have both diagnostic and prognostic significance. The aim of the present study was to identify miRNAs associated with recurrence of stage II CRC, followed up by an investigation of how these potential...... biomarkers functionally influence tumour cell behaviour. TaqMan® Human MicroRNA Array Set v2.0 was use to profile the expression of more than 600 miRNAs in 46 stage II CRC tumours (23 without recurrence and 23 with recurrence). Four miRNAs; were identified as being associated with recurrence of the disease...

  8. CRC DEPLETION CALCULATIONS FOR THE RODDED ASSEMBLIES IN BATCHES 1, 2, 3, AND 1X OF CRYSTAL RIVER UNIT 3

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth D. Wright

    1997-09-03

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain rodded fuel assemblies from batches 1, 2, 3, and 1X of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A rodded assembly is one that contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) for some period of time during its irradiation history. The objective of this analysis is to provide SAS2H calculated isotopic compositions of depleted fuel and depleted burnable poison for each fuel assembly to be used in subsequent CRC reactivity calculations containing the fuel assemblies.

  9. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 1, 2, AND 3 OF CRYSTAL RIVER UNIT 3

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth D. Wright

    1997-07-29

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 1, 2, and 3 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies.

  10. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 8 AND 9 CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wilson, Michael L.

    2001-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 8 and 9 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

  11. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 4 AND 5 OF CRYSTAL RIVER UNIT 3

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth D. Wright

    1997-07-30

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 4 and 5 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies.

  12. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 8 AND 9 CRYSTAL RIVER UNIT 3

    Energy Technology Data Exchange (ETDEWEB)

    Michael L. Wilson

    2001-02-08

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 8 and 9 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies.

  13. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 4 AND 5 OF CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wright, Kenneth D.

    1997-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 4 and 5 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

  14. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 1, 2, AND 3 OF CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wright, Kenneth D.

    1997-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 1, 2, and 3 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

  15. CRC DEPLETION CALCULATIONS FOR THE RODDED ASSEMBLIES IN BATCHES 1, 2, 3, AND 1X OF CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wright, Kenneth D.

    1997-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain rodded fuel assemblies from batches 1, 2, 3, and 1X of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A rodded assembly is one that contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) for some period of time during its irradiation history. The objective of this analysis is to provide SAS2H calculated isotopic compositions of depleted fuel and depleted burnable poison for each fuel assembly to be used in subsequent CRC reactivity calculations containing the fuel assemblies

  16. High reflectance Cr/C multilayer at 250 eV for soft X-ray polarimetry

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Mingwu; Jiang, Li; Zhang, Zhong; Huang, Qiushi [MOE Key Laboratory of Advanced Micro-Structured Materials, Institute of Precision Optical Engineering (IPOE), School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Wang, Zhanshan, E-mail: wangzs@tongji.edu.cn [MOE Key Laboratory of Advanced Micro-Structured Materials, Institute of Precision Optical Engineering (IPOE), School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); She, Rui; Feng, Hua [Department of Engineering Physics, Tsinghua University, Beijing (China); Wang, Hongchang [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2015-10-01

    X-ray reflection near 45° via multilayer mirrors can be used for astronomical polarization measurements. A Cr/C multilayer mirror (designed for X-ray polarimetry at 250 eV), with a period thickness of 3.86 nm and a bi-layer number of 100, was fabricated using direct current magnetron sputtering. Grazing incidence X-ray reflectometry at 8 keV and transmission electron microscopy were used to investigate the multilayer structure. Different models were introduced to fit the hard X-ray reflectivity curve, which indicates that the layer thickness of two materials slightly drifts from the bottom to the top of the stack. Both the chromium and carbon layers are amorphous with asymmetric interfaces, while the Cr-on-C interface is slightly wider. Based on the good quality of the multilayer structure, a high reflectivity of 21.8% for the s-polarized light was obtained at 250 eV at a grazing incidence angle of 40.7°. The fabricated Cr/C multilayer mirror exhibits high reflectivity and polarization levels in the energy region of 240 eV–260 eV. - Highlights: • We fabricated Cr/C multilayer with 3.8 nm d-spacing. • X-ray reflectometry was used to determine the exact structure of Cr/C multilayer. • A high reflectivity of 21.8% for the s-polarized light was obtained at 250 eV. • Both Cr and C were found to be amorphous with slightly asymmetric interfaces. • A 4-layer model was used to fit and explain the results.

  17. The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa

    OpenAIRE

    Dong, Yi-Hu; Zhang, Xi-Fen; Zhang, Lian-Hui

    2013-01-01

    The opportunistic pathogen Pseudomonas aeruginosa utilizes type III secretion system (T3SS) to translocate effector proteins into eukaryotic host cells that subvert normal host cell functions to the benefit of the pathogen, and results in serious infections. T3SS in P. aeruginosa is controlled by a complex system of regulatory mechanisms and signaling pathways. In this study, we described that Crc, an RNA-binding protein, exerts a positive impact on T3SS in P. aeruginosa, as evidenced by prom...

  18. Colorectal cancer predicted risk online (CRC-PRO) calculator using data from the multi-ethnic cohort study.

    Science.gov (United States)

    Wells, Brian J; Kattan, Michael W; Cooper, Gregory S; Jackson, Leila; Koroukian, Siran

    2014-01-01

    Better risk predictions for colorectal cancer (CRC) could improve prevention strategies by allowing clinicians to more accurately identify high-risk individuals. The National Cancer Institute's CRC risk calculator was created by Freedman et al using case control data. An online risk calculator was created using data from the Multi-Ethnic Cohort Study, which followed >180,000 patients for the development of CRC for up to 11.5 years through linkage with cancer registries. Forward stepwise regression tuned to the c statistic was used to select the most important variables for use in separate Cox survival models for men and women. Model accuracy was assessed using 10-fold cross-validation. Patients in the cohort experienced 2762 incident cases of CRC. The final model for men contained age, ethnicity, pack-years of smoking, alcoholic drinks per day, body mass index, years of education, regular use of aspirin, family history of colon cancer, regular use of multivitamins, ounces of red meat intake per day, history of diabetes, and hours of moderate physical activity per day. The final model for women included age, ethnicity, years of education, use of estrogen, history of diabetes, pack-years of smoking, family history of colon cancer, regular use of multivitamins, body mass index, regular use of nonsteroidal anti-inflammatory drugs, and alcoholic drinks per day. The calculator demonstrated good accuracy with a cross-validated c statistic of 0.681 in men and 0.679 in women, and it seems to be well calibrated graphically. An electronic version of the calculator is available at http://rcalc.ccf.org. This calculator seems to be accurate, is user friendly, and has been internally validated in a diverse population.

  19. Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

    LENUS (Irish Health Repository)

    Browne, Patrick

    2010-11-25

    Abstract Background Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5\\' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate

  20. Geographic Variations of Colorectal and Breast Cancer Late-Stage Diagnosis and the Effects of Neighborhood-Level Factors.

    Science.gov (United States)

    Lin, Yan; Wimberly, Michael C

    2017-04-01

    The purpose of this study was to examine the geographic variations of late-stage diagnosis in colorectal cancer (CRC) and breast cancer as well as to investigate the effects of 3 neighborhood-level factors-socioeconomic deprivation, urban/rural residence, and spatial accessibility to health care-on the late-stage risks. This study used population-based South Dakota cancer registry data from 2001 to 2012. A total of 4,878 CRC cases and 6,418 breast cancer cases were included in the analyses. Two-level logistic regression models were used to analyze the risk of late-stage CRC and breast cancer. For CRC, there was a small geographic variation across census tracts in late-stage diagnosis, and residing in isolated small rural areas was significantly associated with late-stage risk. However, this association became nonsignificant after adjusting for census-tract level socioeconomic deprivation. Socioeconomic deprivation was an independent predictor of CRC late-stage risk, and it explained the elevated risk among American Indians. No relationship was found between spatial accessibility and CRC late-stage risk. For breast cancer, no geographic variation in the late-stage diagnosis was observed across census tracts, and none of the 3 neighborhood-level factors was significantly associated with late-stage risk. Results suggested that socioeconomic deprivation, rather than spatial accessibility, contributed to CRC late-stage risks in South Dakota as a rural state. CRC intervention programs could be developed to target isolated small rural areas, socioeconomically disadvantaged areas, as well as American Indians residing in these areas. © 2016 National Rural Health Association.

  1. Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients.

    Directory of Open Access Journals (Sweden)

    Xu Han

    Full Text Available SOX2 is an important stem cell marker and plays important roles in development and carcinogenesis. However, the role of SOX2 in Epithelial-Mesenchymal Transition has not been investigated. We demonstrated, for the first time, that SOX2 is involved in the Epithelial-Mesenchymal Transition (EMT process as knock downof SOX2 in colorectal cancer (CRC SW620 cells induced a Mesenchymal-Epithelial Transition (MET process with recognized changes in the expression of key genes involved in the EMT process including E-cadherin and vimentin. In addition, we provided a link between SOX2 activity and the WNT pathway by showing that knock down of SOX2 reduced the WNT pathway activity in colorectal cancer (CRC cells. We further demonstrated that SOX2 is involved in cell migration and invasion in vitro and in metastasis in vivo for CRC cells, and that the process might be mediated through the MMP2 activity. Finally, an IHC analysis of 44 cases of colorectal cancer patients suggested that SOX2 is a prognosis marker for metastasis of colorectal cancers.

  2. B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jiali Li

    2018-01-01

    Full Text Available Background/Aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Results: Fifty out of 136 CRC patients (37% expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031 and lymph node metastasis (P=0.012. Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289. β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227. Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT.

  3. B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer.

    Science.gov (United States)

    Li, Jiali; Yin, Mingzhu; Song, Wanjing; Cui, Fengyun; Wang, Wei; Wang, Shuyang; Zhu, Hongguang

    2018-01-01

    It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin) and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC) and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Fifty out of 136 CRC patients (37%) expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031) and lymph node metastasis (P=0.012). Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289). β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227). Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT). © 2018 The Author(s). Published by S. Karger AG, Basel.

  4. Stages of endometriosis: Does it affect in vitro fertilization outcome

    Directory of Open Access Journals (Sweden)

    Sonja Pop-Trajkovic

    2014-06-01

    Conclusion: The American Society for Reproductive Medicine classification of endometriosis is useful in predicting IVF outcome. Advanced endometriosis means a worse prognosis for IVF treatment compared to milder stages or tubal factor infertility. The decreased fertilization rate in Stage I/II endometriosis might be a cause of subfertility in these women, as a result of a hostile environment caused by the disease.

  5. Evaluating adhesion reduction efficacy of type I/III collagen membrane and collagen-GAG resorbable matrix in primary flexor tendon repair in a chicken model.

    Science.gov (United States)

    Turner, John B; Corazzini, Rubina L; Butler, Timothy J; Garlick, David S; Rinker, Brian D

    2015-09-01

    Reduction of peritendinous adhesions after injury and repair has been the subject of extensive prior investigation. The application of a circumferential barrier at the repair site may limit the quantity of peritendinous adhesions while preserving the tendon's innate ability to heal. The authors compare the effectiveness of a type I/III collagen membrane and a collagen-glycosaminoglycan (GAG) resorbable matrix in reducing tendon adhesions in an experimental chicken model of a "zone II" tendon laceration and repair. In Leghorn chickens, flexor tendons were sharply divided using a scalpel and underwent repair in a standard fashion (54 total repairs). The sites were treated with a type I/III collagen membrane, collagen-GAG resorbable matrix, or saline in a randomized fashion. After 3 weeks, qualitative and semiquantitative histological analysis was performed to evaluate the "extent of peritendinous adhesions" and "nature of tendon healing." The data was evaluated with chi-square analysis and unpaired Student's t test. For both collagen materials, there was a statistically significant improvement in the degree of both extent of peritendinous adhesions and nature of tendon healing relative to the control group. There was no significant difference seen between the two materials. There was one tendon rupture observed in each treatment group. Surgical handling characteristics were subjectively favored for type I/III collagen membrane over the collagen-GAG resorbable matrix. The ideal method of reducing clinically significant tendon adhesions after injury remains elusive. Both materials in this study demonstrate promise in reducing tendon adhesions after flexor tendon repair without impeding tendon healing in this model.

  6. Fracture Behavior Investigation of a Typical Sandstone Under Mixed-Mode I/II Loading Using the Notched Deep Beam Bending Method

    Science.gov (United States)

    Luo, Y.; Ren, L.; Xie, L. Z.; Ai, T.; He, B.

    2017-08-01

    The brittle fracture behavior of rocks under mixed-mode loading is important in rock engineering. First, a new configuration called the notched deep beam (NDB) specimen was introduced for the fracture testing of rock materials under mixed-mode I/II loading, and a series of finite element analyses were performed to calibrate the dimensionless fracture parameters (i.e., Y I, Y II and T^{*}). The results showed that an NDB specimen subjected to three-point bending is able to generate pure mode I loading, pure mode II loading, and any mixed-mode loading in between. Then, several NDB specimens made of sandstone were used to investigate the brittle fracture behavior of rock under mixed-mode I/II loading. The fracture surfaces were theoretically described using a statistical method, and the results indicated that all the fracture surfaces generated under different mixed-mode loading were statistically identical; to some extent, these results experimentally showed that only tensile fracture occurs under mixed-mode I/II loading. The obtained fracture strengths were then analyzed using several brittle fracture criteria. The empirical criterion, maximum energy release rate criterion, generalized maximum tangential stress (GMTS) criterion, and improved R-criterion accurately predicted the fracture strength envelope of the sandstone. Finally, based on the concepts of point stress and mean stress, the micro-crack zones (MCZs) under different mixed-mode loading were theoretically estimated based on the MTS and GMTS criteria. The critical radius of MCZ in the crack propagation direction was not a constant for all mixed-mode loading conditions regardless of whether the T-stress was considered. This result suggests that the size of the core region used to predict the crack initiation direction and fracture strength based on the GMTS criterion should be chosen more carefully.

  7. The importance of occupancy rather than affinity of CaV(beta) subunits for the calcium channel I-II linker in relation to calcium channel function.

    Science.gov (United States)

    Butcher, Adrian J; Leroy, Jérôme; Richards, Mark W; Pratt, Wendy S; Dolphin, Annette C

    2006-07-15

    The Ca(V)beta subunits of voltage-gated calcium channels regulate the trafficking and biophysical properties of these channels. We have taken advantage of mutations in the tyrosine residue within the alpha interaction domain (AID) in the I-II linker of Ca(V)2.2 which reduce, but do not abolish, the binding of beta1b to the AID of Ca(V)2.2. We have found that the mutation Y388S decreased the affinity of Ca(V)beta1b binding to the Ca(V)2.2 I-II linker from 14 to 329 nm. However, the Y388S mutation had no effect on current density and cell surface expression of Ca(V)2.2/alpha2delta-2/beta1b channels expressed in human embryonic kidney tsA-201 cells, when equivalent proportions of cDNA were used. Furthermore, despite the 24-fold reduced affinity of Ca(V)beta1b for the Y388S I-II linker of Ca(V)2.2, all the key features of modulation as well as trafficking by Ca(V)beta subunits remained intact. This is in contrast to the much more marked effect of the W391A mutation, which abolished interaction with the Ca(V)2.2 I-II linker, and very markedly affected the trafficking of the channels. However, using the Xenopus oocyte expression system, where expression levels can be accurately titrated, when Ca(V)beta1b cDNA was diluted 50-fold, all evidence of interaction with Ca(V)2.2 Y388S was lost, although wild-type Ca(V)2.2 was still normally modulated by the reduced concentration of beta1b. These results indicate that high affinity interaction with the alpha1 subunit is not necessary for any of the modulatory effects of Ca(V)beta subunits, but occupancy of the interaction site is important, and this will occur, despite the reduced affinity, if the Ca(V)beta subunit is present in sufficient excess.

  8. Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Andri M.T. Lubis

    2017-04-01

    Full Text Available Background: Glucosamine, chondroitinsulfate are frequently used to prevent further joint degeneration in osteoarthritis (OA. Methylsulfonylmethane (MSM is a supplement containing organic sulphur and also reported to slow anatomical joint progressivity in the knee OA. The MSM is often combined with glucosamine and chondroitin sulfate. However, there are controversies whether glucosamine-chondroitin sulfate or their combination with methylsulfonylmethane could effectively reduce pain in OA. This study is aimed to compare clinical outcome of glucosamine-chondroitin sulfate (GC, glucosamine-chondroitin sulfate-methylsulfonylmethane (GCM, and placeboin patients with knee osteoarthritis (OA Kellgren-Lawrence grade I-II. Methods: a double blind, randomized controlled clinical trial was conducted on 147 patients with knee OA Kellgren-Lawrence grade I-II. Patients were allocated by permuted block randomization into three groups: GC (n=49, GCM (n=50, or placebo (n=48 groups. GC group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of saccharumlactis; GCM group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of MSM; while placebo group received three matching capsules of saccharumlactis. The drugs were administered once daily for 3 consecutive months VAS and WOMAC scores were measured before treatment, then at 4th, 8th and 12th week after treatment. Results: on statistical analysis it was found that at the 12th week, there are significant difference between three treatment groups on the WOMAC score (p=0.03 and on the VAS score (p=0.004. When analyzed between weeks, GCM treatment group was found statistically significant on WOMAC score (p=0.01 and VAS score (p<0.001. Comparing the score difference between weeks, WOMAC score analysis showed significant difference between GC, GCM, and placebo in week 4 (p=0.049 and week 12 (p=0.01. In addition, VAS score also showed significant difference between groups in week 8 (p=0.006 and week 12 (p<0.001. Conclusion: combination of glucosamine-chondroitinsulfate-methylsulfonylmethane showed clinical benefit for patients with knee OAK ellgren-Lawrence grade I-II compared with GC and placebo. GC did not make clinical improvement in overall groups of patients with knee OA Kellgren Lawrence grade I-II.

  9. La religión practicada por los militares del Ejército Romano de Hispania durante el Alto Imperio Romano (siglos I-III)

    OpenAIRE

    Luis Sagredo San Eustaquio; Agustín Jiménez de Furundarena

    1996-01-01

    El estudio de !a religión practicada en las unidades del ejército romano ha sido siempre un tema que ha apasionado a los investigadores del mundo romano, disponiendo de una serie de obras generales referidas a este apartado de la vida militar durante el Imperio. Sin embargo, la religión practicada por el ejército romano acuartelado en Hispania durante el Alto imperio (siglos i-iii) no ha sido, hasta el presente, analizada de una forma monográfica. La base de trabajo para ...

  10. Un ejemplo de crono-estratigrafía en un sitio con superposición arquitectónica: Piruru-Unidad I/II

    Directory of Open Access Journals (Sweden)

    1985-01-01

    Full Text Available Résumé: A partir de l'étude de quatre coupes, on présente la stratigraphie de l'Unité I/II du site de Piruru, où se superposent des architectures tardives, formatives et précéramiques. On explique la formation du remplissage archéologique, qui atteint 3,60m d'épaisseur, en mettant en rapport l'accumulation des dépôts avec les activités constructrices. Du point de vue de la construction et de l'occupation, on définit sept événements majeurs qui se répartissent, dans une chronologie relative, en phases et sous phases. Con el estudio de cuatro cortes, se presenta la estratigrafía de la Unidad I/II, en el sitio de Piruru, donde se superponen estructuras arquitectónicas tardías, formativas y precerámicas. Se explica la formación del relleno arqueológico, que alcanza 3,60m de espesor, relacionando la acumulación de depósitos con la actividad constructora. Se definen siete acontecimientos mayores, en construcción y ocupación, que se reparten, en una cronología relativa, en fases y subfases.

  11. Effect of Compressive Mode I on the Mixed Mode I/II Fatigue Crack Growth Rate of 42CrMo4

    Science.gov (United States)

    Heirani, Hasan; Farhangdoost, Khalil

    2018-01-01

    Subsurface cracks in mechanical contact loading components are subjected to mixed mode I/II, so it is necessary to evaluate the fatigue behavior of materials under mixed mode loading. For this purpose, fatigue crack propagation tests are performed with compact tension shear specimens for several stress intensity factor (SIF) ratios of mode I and mode II. The effect of compressive mode I loading on mixed mode I/II crack growth rate and fracture surface is investigated. Tests are carried out for the pure mode I, pure mode II, and two different mixed mode loading angles. On the basis of the experimental results, mixed mode crack growth rate parameters are proposed according to Tanaka and Richard with Paris' law. Results show neither Richard's nor Tanaka's equivalent SIFs are very useful because these SIFs depend strongly on the loading angle, but Richard's equivalent SIF formula is more suitable than Tanaka's formula. The compressive mode I causes the crack closure, and the friction force between the crack surfaces resists against the crack growth. In compressive loading with 45° angle, d a/d N increases as K eq decreases.

  12. From Large-Scale Synthesis to Lighting Device Applications of Ternary I-III-VI Semiconductor Nanocrystals: Inspiring Greener Material Emitters.

    Science.gov (United States)

    Chen, Bingkun; Pradhan, Narayan; Zhong, Haizheng

    2018-01-18

    Quantum dots with fabulous size-dependent and color-tunable emissions remained as one of the most exciting inventories in nanomaterials for the last 3 decades. Even though a large number of such dot nanocrystals were developed, CdSe still remained as unbeatable and highly trusted lighting nanocrystals. Beyond these, the ternary I-III-VI family of nanocrystals emerged as the most widely accepted greener materials with efficient emissions tunable in visible as well as NIR spectral windows. These bring the high possibility of their implementation as lighting materials acceptable to the community and also to the environment. Keeping these in mind, in this Perspective, the latest developments of ternary I-III-VI nanocrystals from their large-scale synthesis to device applications are presented. Incorporating ZnS, tuning the composition, mixing with other nanocrystals, and doping with Mn ions, light-emitting devices of single color as well as for generating white light emissions are also discussed. In addition, the future prospects of these materials in lighting applications are also proposed.

  13. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse

    Directory of Open Access Journals (Sweden)

    Rabeah A. Al-Temaimi

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT. Resultant genes were classified based on gene ontology (GO, which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.

  14. Pickled meat consumption and colorectal cancer (CRC): a case-control study in Newfoundland and Labrador, Canada.

    Science.gov (United States)

    Squires, Josh; Roebothan, Barbara; Buehler, Sharon; Sun, Zhuoyu; Cotterchio, Michelle; Younghusband, Ban; Dicks, Elizabeth; Mclaughlin, John R; Parfrey, Patrick S; Wang, Peizhong Peter

    2010-09-01

    Although a large body of epidemiological research suggests that red meat intake increases the risk of colorectal cancer, little is known regarding how such an association varies across populations and types of red meat. The objective of this study was to assess whether an association exists between the intakes of total red meat and pickled red meat and the risk of colorectal cancer in study subjects residing in Newfoundland and Labrador. This case-control study of 1,204 residents of Newfoundland and Labrador was part of a larger study on colorectal cancer. Personal history food frequency questionnaires were used to collect retrospective data from 518 individuals diagnosed with colorectal cancer and 686 controls. Intakes were ranked and divided into tertiles. Logistic regression was used to examine the possible association between meat intakes and colorectal cancer diagnosis while controlling for possible confounding factors. A positive, but non-statistically significant, association between total red meat intake and CRC was observed in this study. Pickled red meat consumption was found to be significantly associated with an increased risk of CRC (men, OR = 2.07, 95% CI 1.37-3.15; women, OR = 2.51, 95% CI 1.45-4.32), the odds ratios increasing with each tertile of consumption, suggesting a dose-response effect. Intake of pickled red meat appears to increase the risk of colorectal cancer in Newfoundland and Labrador.

  15. The KRAS Strip Assay for detection of KRAS mutation in Egyptian patients with colorectal cancer (CRC): A pilot study

    International Nuclear Information System (INIS)

    Abd El Kader, Y.; Safwat, E.; Kassem, H.A.; Kassem, N.M.; Emera, G.

    2013-01-01

    Background: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefltinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. Purpose: Detection of KRAS mutation in Egyptian colorectal cancer (CRC) patients by the KRAS Strip Assay. Methods: Examination of 20 colorectal cancer (CRC) patients is done to detect KRAS mutations by KRAS Strip Assay. For the Strip Assay, a mutant-enriched PCR was followed by hybridization to KRAS-specific probes bound to a nitrocellulose strip. Results: Among 20 patients, KRAS mutations were identified in 80% of patients by the KRAS Strip Assay. Conclusions: Our preliminary results suggest that KRAS Strip Assay is an alternative to protocols currently in use for KRAS mutation detection

  16. Identification and Construction of Combinatory Cancer Hallmark-Based Gene Signature Sets to Predict Recurrence and Chemotherapy Benefit in Stage II Colorectal Cancer.

    Science.gov (United States)

    Gao, Shanwu; Tibiche, Chabane; Zou, Jinfeng; Zaman, Naif; Trifiro, Mark; O'Connor-McCourt, Maureen; Wang, Edwin

    2016-01-01

    Decisions regarding adjuvant therapy in patients with stage II colorectal cancer (CRC) have been among the most challenging and controversial in oncology over the past 20 years. To develop robust combinatory cancer hallmark-based gene signature sets (CSS sets) that more accurately predict prognosis and identify a subset of patients with stage II CRC who could gain survival benefits from adjuvant chemotherapy. Thirteen retrospective studies of patients with stage II CRC who had clinical follow-up and adjuvant chemotherapy were analyzed. Respective totals of 162 and 843 patients from 2 and 11 independent cohorts were used as the discovery and validation cohorts, respectively. A total of 1005 patients with stage II CRC were included in the 13 cohorts. Among them, 84 of 416 patients in 3 independent cohorts received fluorouracil-based adjuvant chemotherapy. Identification of CSS sets to predict relapse-free survival and identify a subset of patients with stage II CRC who could gain substantial survival benefits from fluorouracil-based adjuvant chemotherapy. Eight cancer hallmark-based gene signatures (30 genes each) were identified and used to construct CSS sets for determining prognosis. The CSS sets were validated in 11 independent cohorts of 767 patients with stage II CRC who did not receive adjuvant chemotherapy. The CSS sets accurately stratified patients into low-, intermediate-, and high-risk groups. Five-year relapse-free survival rates were 94%, 78%, and 45%, respectively, representing 60%, 28%, and 12% of patients with stage II disease. The 416 patients with CSS set-defined high-risk stage II CRC who received fluorouracil-based adjuvant chemotherapy showed a substantial gain in survival benefits from the treatment (ie, recurrence reduced by 30%-40% in 5 years). The CSS sets substantially outperformed other prognostic predictors of stage 2 CRC. They are more accurate and robust for prognostic predictions and facilitate the identification of patients with stage

  17. Impact on the display of power cheerleading ability of university students I-II levels of accreditation

    Directory of Open Access Journals (Sweden)

    N.V. Kryvoruchko

    2013-09-01

    Full Text Available Reflects the dynamics of indicators of the level of development of power abilities of students under the influence of specially selected exercises cheerleading. The study involved 385 students (age 15-17 years. The level of the forces will determine by tests: flexion-extension hand-ups, lifting the torso in the saddle for 1 minute, jumping on one leg with the progress, carpal dynamometry. Revealed low levels of manifestation of the power in the first stage. Most significantly improved the results of flexion-extension hand-ups (I course to 32,28%, II course at 21,77%, III course for 25.60%;. According to the results of the lifting body in the saddle improved results of 12.41%, 10.80%, 11.98%, respectively. According to the results of the hops on one foot with the progress - by 5.78%, 4.70%, 4.97%, respectively. According to the wrist of the dynamometer, at 6.31%, 5.36%, 5.89% respectively. The most significant growth results have been observed mainly at students aged 15 years.

  18. Viability study for application of combined reheater cycle (CRC) to fluidized bed combustion plants; Estudio de Viabilidad para la Aplicacion del Ciclo de Recalentamiento Combinado (CRC) a Plantas de Combustion de Lecho Fuido Atmosferico

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    Basically, the project try to analyze the application viability of a first reheating in steam cycles of little power plants, useful mainly for biomass and wastes, in our case with coal blends; and a second reheating of the steam in conventional and fluidized bed combustion plants. Using in both cases the thermic energy of the exhaust gases from one gas turbine. The advantages of the CRC cycle are: (1) Reduction of the moisture in the turbine, increasing the energy efficiency and blade protection. (2) To take advantage of the waste gas energy from the gas turbine in optimum way. (3) Great operation flexibility under good efficiency results. In general, the system can use the synergy between gas, coal and waste energies with the highest global efficiency. (Author)

  19. Is Travel Time to Colonoscopy Associated With Late-Stage Colorectal Cancer Among Medicare Beneficiaries in Iowa?

    Science.gov (United States)

    Charlton, Mary E; Matthews, Kevin A; Gaglioti, Anne; Bay, Camden; McDowell, Bradley D; Ward, Marcia M; Levy, Barcey T

    2016-09-01

    Colorectal cancer (CRC) screening has been shown to decrease the incidence of late-stage colorectal cancer, yet a substantial proportion of Americans do not receive screening. Those in rural areas may face barriers to colonoscopy services based on travel time, and previous studies have demonstrated lower screening among rural residents. Our purpose was to assess factors associated with late-stage CRC, and specifically to determine if longer travel time to colonoscopy was associated with late-stage CRC among an insured population in Iowa. SEER-Medicare data were used to identify individuals ages 65 to 84 years old diagnosed with CRC in Iowa from 2002 to 2009. The distance between the centroid of the ZIP code of residence and the ZIP code of colonoscopy was computed for each individual who had continuous Medicare fee-for-service coverage for a 3- to 4-month period prior to diagnosis, and a professional claim for colonoscopy within that time frame. Demographic characteristics and travel times were compared between those diagnosed with early- versus late-stage CRC. Also, demographic differences between those who had colonoscopy claims identified within 3-4 months prior to diagnosis (81%) were compared to patients with no colonoscopy claims identified (19%). A total of 5,792 subjects met inclusion criteria; 31% were diagnosed with early-stage versus 69% with late-stage CRC. Those divorced or widowed (vs married) were more likely to be diagnosed with late-stage CRC (OR: 1.20, 95% CI: 1.06-1.37). Travel time was not associated with diagnosis of late-stage CRC. Among a Medicare-insured population, there was no relationship between travel time to colonoscopy and disease stage at diagnosis. It is likely that factors other than distance to colonoscopy present more pertinent barriers to screening in this insured population. Additional research should be done to determine reasons for nonadherence to screening among those with access to CRC screening services, given that over

  20. A comparison of stage of presentation for pancreatic and colorectal cancer in Pennsylvania 2000-2005.

    Science.gov (United States)

    Chirumbole, Mark; Gusani, Niraj; Howard, Alicia; Leonard, Tim; Lewis, Peter; Muscat, Josh

    2009-08-01

    The goal of this study was to examine how rurality, socioeconomic status (SES) and access to medical care are related to the stage at presentation of patients with colorectal (CRC) and pancreatic cancer (PC) in Pennsylvania. Incident CRC and PC cases were identified from the Pennsylvania Department of Health. Demographic, SES, and access variables were collected at the county level. Increased urbanization, younger age, and male gender were shown to be significantly related to later stage at diagnosis for PC. Age and education level were significant predictors of the rate of PC, while age, education level, insurance status, rurality, and the ratio of oncologists to primary care physicians were significant predictors of the rate of CRC. Based on county-level data, urban residence, younger age, and male gender were shown to be predictors of later stage at diagnosis for PC. These findings should help guide further research into factors that may be important predictors of later stage of diagnosis.

  1. Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Shiga

    2016-01-01

    Full Text Available Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6 in colorectal cancer (CRC. Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS and disease-free survival (DFS rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

  2. Effects of gentiana scabra bage on expression of hepatic type I, III collagen proteins in Paragonimus skrjabini rats with liver fibrosis.

    Science.gov (United States)

    Qu, Zhao-Xia; Li, Fang; Ma, Chao-Dong; Liu, Jun; Li, Shu-De; Wang, Wen-Lin

    2015-01-01

    To explore the effects of gentiana scabra bage on the expression of hepatic collagen proteins in Paragonimus skrjabini rats with liver fibrosis. Immunohistochemical technique was used to observe the changes of content of hepatic type I, III collagen proteins in Paragonimus skrjabini rats with liver fibrosis before and after the gentiana scabra bage treatmeat. Comparing with the model group, changes of hepatic type I and type III collagen proteins in gentiana scabra bage treated group were significantly weakened. Gentiana scabra bage treatment can reduce the content of hepatic type III and type I collagen protein significantly in Paragonimus skrjabini rats with liver fibrosis, thereby, playing the role against hepatic fibrosis. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  3. I-III-VI.sub.2 based solar cell utilizing the structure CuInGaSe.sub.2 CdZnS/ZnO

    Science.gov (United States)

    Chen, Wen S.; Stewart, John M.

    1992-01-07

    A thin film I-III-VI.sub.2 based solar cell having a first layer of copper indium gallium selenide, a second layer of cadmium zinc sulfide, a double layer of zinc oxide, and a metallization structure comprised of a layer of nickel covered by a layer of aluminum. An optional antireflective coating may be placed on said metallization structure. The cadmium zinc sulfide layer is deposited by means of an aqueous solution growth deposition process and may actually consist of two layers: a low zinc content layer and a high zinc content layer. Photovoltaic efficiencies of 12.5% at Air Mass 1.5 illumination conditions and 10.4% under AMO illumination can be achieved.

  4. Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

    Directory of Open Access Journals (Sweden)

    Van Nguyen Thu

    2011-09-01

    Full Text Available Abstract Background Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. Materials and Methods We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA Results Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51. Maximal grade 1, 2, and 3 acute ( Conclusions Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.

  5. Imposition of Antidumping Duty (BAMD Towards China’s Cold Rolled Coil/Sheet (CRC/S Products

    Directory of Open Access Journals (Sweden)

    Lila Pratiwi

    2013-05-01

    Full Text Available Steel industry is a strategic sector in the economy of a country. Steel industry in Indonesia has not been able to fulfill their domestic demand that is still necessary to import steel product. However, many of these imported products are sold at dumping prices, especially those from china giving rise to unfair trade. One of trade remedy measures as a result of unfair trade remedies can recover trough the imposition of antidumping duty. In 2013, Indonesia imposes antidumping duty for Cold Rolled Coil/Sheet (CRC/S from China and other countries. Imposition of antidumping duty will be analyzed descriptively with the antidumping agreement conformity. While, it cannot be denied that political factors also determine imposition of antidumping duty. It is need to use analytical theory of justice in order to enforce fair-trade

  6. Long-term follow-up of pepsinogen I/II ratio after eradication of Helicobacter pylori in patients who underwent endoscopic mucosal resection for gastric cancer.

    Science.gov (United States)

    Nam, Su Youn; Jeon, Seong Woo; Lee, Hyun Seok; Kwon, Yong Hwan; Park, Haeyoon; Choi, Jin Woo

    2017-05-01

    Although the pepsinogen I/II (PGI/II) ratio after Helicobacter pylori eradication is recovered at short-term follow-up, long-term follow-up studies of PGI/II are rare. A total of 773 patients with gastric cancer who underwent endoscopic resection and pepsinogen and H. pylori tests were enrolled. H. pylori was eradicated in these patients. Endoscopic and pepsinogen tests were performed every year. A low PGI/II ratio was defined as ≤3. The PGI/II ratio was higher in non-infected patients (n=275, 4.99) than infected patients (n=498, 3.53). After H. pylori eradication, the PGI/II ratio increased to 5.81 and 5.63 after 1 and 2 years (each ppylori eradication group became similar to that of the H. pylori-negative group at 3 (4.48 vs. 4.34), 4 (4.88 vs. 4.34), and 5 years (4.89 vs. 4.23). The adjusted odds ratios for a lower PG I/II ratio in the non-eradication group compared to the eradication group were 4.78 (95% CI 2.15-10.67) after 1year and 8.13 (95% CI 2.56-25.83) after 2 years. After H. pylori eradication, the PGI/II ratio increased and was similar to that of H. pylori-negative controls for up to 5 years of follow-up. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. The PACOVAR-trial: A phase I/II study of pazopanib (GW786034 and cyclophosphamide in patients with platinum-resistant recurrent, pre-treated ovarian cancer

    Directory of Open Access Journals (Sweden)

    Schmidt Marcus

    2011-10-01

    Full Text Available Abstract Background The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC is poor. There is no standard treatment available. Emerging evidence suggests a major role for antiangiogenic treatment modalities in EOC, in particular in combination with the metronomic application of low dose chemotherapy. The novel, investigational oral antiangiogenic agent pazopanib targeting vascular endothelial growth factor receptor (VEGFR, platelet-derived growth factor receptor (PDGFR and c-kit is currently being studied in different tumour types and is already used as first line therapy in recurrent renal cell carcinoma. A combined therapy consisting of pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, pretreated EOC. Methods/design This study is designed as a multicenter phase I/II trial evaluating the optimal dose for pazopanib (phase I as well as activity and tolerability of a combination regimen consisting of pazopanib and metronomic cyclophosphamide in the palliative treatment of patients with recurrent, platinum-resistant, pre-treated ovarian cancer (phase II. The patient population includes patients with histologically or cytologically confirmed diagnosis of EOC, cancer of the fallopian tube or peritoneal cancer which is platinumresistant or -refractory. Patients must have measurable disease according to RECIST criteria and must have failed available standard chemotherapy. Primary objectives are determination of the optimal doses for pazopanib (phase I and the overall response rate according to RECIST criteria (phase II. Secondary objectives are time to progression, overall survival, safety and tolerability. The treatment duration is until disease progression or intolerability of study drug regimen (with a maximum of 13 cycles up to 52 weeks per subject. Discussion The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer. Trial registration ClinicalTrials.gov: NCT01238770

  8. The PACOVAR-trial: A phase I/II study of pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant recurrent, pre-treated ovarian cancer

    International Nuclear Information System (INIS)

    Eichbaum, Michael; Fersis, Nikos; Schmidt, Marcus; Wallwiener, Markus; Schneeweiss, Andreas; Sohn, Christof; Mayer, Christine; Eickhoff, Regina; Bischofs, Esther; Gebauer, Gerhard; Fehm, Tanja; Lenz, Florian; Fricke, Hans-Christian; Solomayer, Erich

    2011-01-01

    The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC) is poor. There is no standard treatment available. Emerging evidence suggests a major role for antiangiogenic treatment modalities in EOC, in particular in combination with the metronomic application of low dose chemotherapy. The novel, investigational oral antiangiogenic agent pazopanib targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit is currently being studied in different tumour types and is already used as first line therapy in recurrent renal cell carcinoma. A combined therapy consisting of pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, pretreated EOC. This study is designed as a multicenter phase I/II trial evaluating the optimal dose for pazopanib (phase I) as well as activity and tolerability of a combination regimen consisting of pazopanib and metronomic cyclophosphamide in the palliative treatment of patients with recurrent, platinum-resistant, pre-treated ovarian cancer (phase II). The patient population includes patients with histologically or cytologically confirmed diagnosis of EOC, cancer of the fallopian tube or peritoneal cancer which is platinumresistant or -refractory. Patients must have measurable disease according to RECIST criteria and must have failed available standard chemotherapy. Primary objectives are determination of the optimal doses for pazopanib (phase I) and the overall response rate according to RECIST criteria (phase II). Secondary objectives are time to progression, overall survival, safety and tolerability. The treatment duration is until disease progression or intolerability of study drug regimen (with a maximum of 13 cycles up to 52 weeks per subject). The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01238770

  9. A phase I/II study on stereotactic body radiotherapy with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm for lung tumors.

    Science.gov (United States)

    Iwata, Hiromitsu; Ishikura, Satoshi; Murai, Taro; Iwabuchi, Michio; Inoue, Mitsuhiro; Tatewaki, Koshi; Ohta, Seiji; Yokota, Naoki; Shibamoto, Yuta

    2017-08-01

    In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade ≥3 radiation pneumonitis (RP) within 180 days of the start of SBRT. The secondary endpoint was local control and overall survival rates. Five patients were initially enrolled at level 1 [50 Gy/4 fractions (Fr)]; during the observation period, level 0 (45 Gy/4 Fr) was opened. The dose was escalated to the next level when grade ≥3 RP was observed in 0 out of 5 or 1 out of 10 patients. Virtual quality assurance planning was performed for 60 Gy/4 Fr; however, dose constraints for the organs at risk did not appear to be within acceptable ranges. Therefore, level 2 (55 Gy/4 Fr) was regarded as the upper limit. After the recommended dose (RD) was established, 15 additional patients were enrolled at the RD. The prescribed dose was normalized at the 95% volume border of the planning target volume based on the Monte Carlo algorithm. Between September 2011 and September 2015, 40 patients (primary 30; metastasis 10) were enrolled. Five patients were enrolled at level 0, 15 at level 1, and 20 at level 2. Only one grade 3 RP was observed at level 1. Two-year local control and overall survival rates were 98 and 81%, respectively. The RD was 55 Gy/4 Fr. SBRT with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm was tolerated well and appeared to be effective for solitary lung tumors.

  10. EFECTO DE LA ADICIÓN DE CARRAGENINA KAPPA I.II Y GOMA TARA SOBRE CARACTERÍSTICAS DE CALIDAD DEL JAMÓN DE CERDO PICADO Y COCIDO EFFECT OF THE ADDITION OF KAPPA I.II CARRAGEENAN AND TARA GUM ON QUALITY CHARACTERISTICS OF COOKED AND CHOPPED PORK HAMS

    OpenAIRE

    Diego Alonso Restrepo Molina; Fabio Alexander Molina Cote; Kenneth Roy Cabrera Torres

    2010-01-01

    Se evaluaron sinéresis, color y dureza instrumental y, sensorialmente las características de olor, sabor, color y dureza en jamones inyectados, cocidos y picados de cerdo, los cuales se habían elaborado aplicando en la salmuera de inyección una mezcla de hidrocoloides compuesta por carragenina kappa I.II y goma tara en una proporción de 79:21, en niveles del 1% y 1,2%, usando tres repeticiones para el estudio. Los jamones así elaborados se compararon contra un jamón testigo, elaborado sin el ...

  11. Modeling how substitution of sedentary behavior with standing or physical activity is associated with health-related quality of life in colorectal cancer survivors

    OpenAIRE

    van Roekel, Eline H.; Bours, Martijn J. L.; Breedveld-Peters, Jos? J. L.; Willems, Paul J. B.; Meijer, Kenneth; Kant, IJmert; van den Brandt, Piet A.; Beets, Geerard L.; Sanduleanu, Silvia; Weijenberg, Matty P.

    2016-01-01

    Purpose Previous research indicates that sedentary behavior is unfavorably associated with health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. Using isotemporal substitution modeling, we studied how substituting sedentary behavior with standing or physical activity was associated with HRQoL in CRC survivors, 2?10?years post-diagnosis. Methods A cross-sectional study was conducted in stage I?III CRC survivors (n?=?145) diagnosed at Maastricht University Medical Center+...

  12. Anchoring wind turbine towers in steel using construction elements of concrete and CRC; Compact reinforced composite; Forankring af vindmoelletaarne i staal ved anvendelse af konstruktionselementer i beton og CRC

    Energy Technology Data Exchange (ETDEWEB)

    2005-07-15

    During the past 25 to 30 years extensive R and D projects within concrete technology have been carried out. The result of this work is high-strength concrete that consists of fibres and reinforced materials. Traditionally wind turbine towers are fastened to the foundation using an embedded steel ring with a flange ring in the top surface. The maximum tower diameter of 4.5 m, set on the grounds of road transport, is now playing a significant role in this connection. This report presents results from a study of the possibilities for using a connecting piece made from concrete anchored directly in the turbine foundations' base and placed on top of the foundation bolted to the towers' bottom flange. High-strength concrete has been studied as an alternative to ordinary concrete. the results show that anchoring the tower in the foundation using reinforcement passively anchored in the bottom of the foundation and supported by a concrete/CRC connecting piece has a number of advantages compared to traditional solutions. (BA)

  13. A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 5-year results of local control and cosmetic outcome

    International Nuclear Information System (INIS)

    Kawamura, Mariko; Itoh, Yoshiyuki; Sawaki, Masataka; Kikumori, Toyone; Tsunoda, Nobuyuki; Kamomae, Takeshi; Kubota, Seiji; Okada, Tohru; Nakahara, Rie; Ito, Junji; Hayashi, Hironori; Naganawa, Shinji

    2015-01-01

    To date, there are no reports of intraoperative radiotherapy (IORT) use with long-term follow up as a method of accelerated partial breast irradiation (APBI) in Asian countries. We initiated a prospective phase I/II clinical trial of IORT in Japan in 2007, and herein, we report the 5-year follow-up results. The following inclusion criteria were used for enrollment in the trial: (1) tumor size < 2.5 cm, (2) desire for breast-conserving surgery, (3) age >50 years, and (4) negative margins after resection. In February 2009, the eligibility criteria were changed to include only patients with sentinel lymph node-negative disease. In phase I, the radiotherapy dose was escalated from 19 Gy/fr to 21 Gy/fr, incremented by 1 Gy per step, with 3 patients in each step. Doses were escalated after all patients in the preceding cohort had completed treatment and exhibited only grade 1 or 2 toxicities at a given dose level. The recommended phase II dose was set at 21 Gy at 90 % isodose. The primary endpoint was early toxicity. Secondary endpoints were long-term efficacy and late toxicity. In addition, Hypertrophic scarring was evaluated retrospectively as a cosmetic outcome by a radiation oncologist. Between December 2007 and March 2010, 32 women with breast cancer were enrolled in the trial. The median age was 65 years (51–80 years), and the median follow-up time was 6 years. No recurrence or metastasis was observed in any patient. Grade 2 fibrosis was detected in 3 patients as an acute adverse event and in 2 patients as a late adverse event. Ten patients developed a hypertrophic scar 1 year after the IORT; the number of patients decreased to 7 in the 3 years of follow-up. The first group of female Asian patients tolerated the treatment with IORT in this Phase I/II study and remained recurrence-free for more than 5 years after treatment. However, 24 % of the patients developed hypertrophic scarring, an event that is being further examined in our ongoing multi-center Phase II trial of IORT for early breast cancer

  14. Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Debus Juergen

    2011-04-01

    Full Text Available Abstract Background The efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of tumor specific effector T cells in the tumor. Accumulating evidence exists on the ability of ionizing radiation to modify the tumor microenvironment and generate inflammation. The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with pancreatic cancer. Methods/Design This trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. Patients who are candidates for resection of pancreatic cancer will be randomized into 4 arms. A total of 40 patients will be enrolled. The patients receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their pancreatic carcinoma. Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include local tumor control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of tumor reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrolment of 20 patients for safety reasons. The evaluation of the primary endpoint will start four weeks after the last patient's enrolment. Discussion This trial will answer the question whether a low dose radiotherapy localized to the pancreatic tumor only can increase the number of tumor infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive value of radiation-induced T cell activity along with transcriptomic and proteomic data with respect to clinical outcome. Trial registration ClinicalTrials.gov - NCT01027221

  15. Slender CRC Columns

    DEFF Research Database (Denmark)

    Aarup, Bendt; Jensen, Lars Rom; Ellegaard, Peter

    2005-01-01

    in standard fire conditions. The tests showed good correlation between test results and results calculated according to established deisgn guides. The fire tests demonstrate that the load capacity of slender columns can be reduced very quickly due to thermal stresses and a reduction of stiffness - also...... in cases where temperature at the rebar is still relatively low. However, guidelines for achieving acceptable fire resistance can be determined based on the test results....

  16. Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence.

    Science.gov (United States)

    den Uil, Sjoerd H; Coupé, Veerle M H; Linnekamp, Janneke F; van den Broek, Evert; Goos, Jeroen A C M; Delis-van Diemen, Pien M; Belt, Eric J Th; van Grieken, Nicole C T; Scott, Patricia M; Vermeulen, Louis; Medema, Jan Paul; Bril, Herman; Stockmann, Hein B A C; Cormier, Robert T; Meijer, Gerrit A; Fijneman, Remond J A

    2016-12-06

    Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at risk for recurrence is an unmet clinical need. KCNQ1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with CRC liver metastases. In this study the prognostic value of KCNQ1 in stage II and stage III colon cancer patients was examined. KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. Subsequently, KCNQ1 protein expression was evaluated in an independent cohort of 386 stage II and stage III colon cancer patients by immunohistochemistry of tissue microarrays. Low KCNQ1 mRNA expression in stage II microsatellite stable (MSS) colon cancers was associated with poor disease-free survival (DFS) (P=0.025). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in stage II MSS (PKCNQ1 seemed an independent prognostic value in addition to other high-risk parameters like angio-invasion, nodal stage and microsatellite instability-status. We conclude that KCNQ1 is a promising biomarker for prediction of disease recurrence and may aid stratification of patients with stage II MSS colon cancer for adjuvant chemotherapy.

  17. Hypoxia Is a Critical Parameter for Chondrogenic Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells in Type I/III Collagen Sponges

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    Tangni Gómez-Leduc

    2017-09-01

    Full Text Available Umbilical cord blood (UCB is an attractive alternative to bone marrow for isolation of mesenchymal stem cells (MSCs to treat articular cartilage defects. Here, we set out to determine the growth factors (bone morphogenetic protein 2 (BMP-2 and transforming growth factor-β (TGF-β1 and oxygen tension effects during chondrogenesis of human UCB-MSCs for cartilage engineering. Chondrogenic differentiation was induced using 3D cultures in type I/III collagen sponges with chondrogenic factors in normoxia (21% O2 or hypoxia (<5% O2 for 7, 14 and 21 days. Our results show that UCB-MSCs can be committed to chondrogenesis in the presence of BMP-2+TGF-β1. Normoxia induced the highest levels of chondrocyte-specific markers. However, hypoxia exerted more benefit by decreasing collagen X and matrix metalloproteinase-13 (MMP13 expression, two chondrocyte hypertrophy markers. However, a better chondrogenesis was obtained by switching oxygen conditions, with seven days in normoxia followed by 14 days in hypoxia, since these conditions avoid hypertrophy of hUCB-MSC-derived chondrocytes while maintaining the expression of chondrocyte-specific markers observed in normoxia. Our study demonstrates that oxygen tension is a key factor for chondrogenesis and suggests that UBC-MSCs 3D-culture should begin in normoxia to obtain a more efficient chondrocyte differentiation before placing them in hypoxia for chondrocyte phenotype stabilization. UCB-MSCs are therefore a reliable source for cartilage engineering.

  18. Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition

    Directory of Open Access Journals (Sweden)

    Schlichter Rémy

    2008-05-01

    Full Text Available Abstract Background Recent evidence suggests that oxytocin (OT, secreted in the superficial spinal cord dorsal horn by descending axons of paraventricular hypothalamic nucleus (PVN neurons, produces antinociception and analgesia. The spinal mechanism of OT is, however, still unclear and requires further investigation. We have used patch clamp recording of lamina II neurons in spinal cord slices and immunocytochemistry in order to identify PVN-activated neurons in the superficial layers of the spinal cord and attempted to determine how this neuronal population may lead to OT-mediated antinociception. Results We show that OT released during PVN stimulation specifically activates a subpopulation of lamina II glutamatergic interneurons which are localized in the most superficial layers of the dorsal horn of the spinal cord (lamina I-II. This OT-specific stimulation of glutamatergic neurons allows the recruitment of all GABAergic interneurons in lamina II which produces a generalized elevation of local inhibition, a phenomenon which might explain the reduction of incoming Aδ and C primary afferent-mediated sensory messages. Conclusion Our results obtained in lamina II of the spinal cord provide the first clear evidence of a specific local neuronal network that is activated by OT release to induce antinociception. This OT-specific pathway might represent a novel and interesting therapeutic target for the management of neuropathic and inflammatory pain.

  19. Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis

    Directory of Open Access Journals (Sweden)

    Shunsuke Baba

    2016-01-01

    Full Text Available Regenerative medicine is emerging as a promising option, but the potential of autologous stem cells has not been investigated well in clinical settings of periodontal treatment. In this clinical study, we evaluated the safety and efficacy of a new regenerative therapy based on the surgical implantation of autologous mesenchymal stem cells (MSCs with a biodegradable three-dimensional (3D woven-fabric composite scaffold and platelet-rich plasma (PRP. Ten patients with periodontitis, who required a surgical procedure for intrabony defects, were enrolled in phase I/II trial. Once MSCs were implanted in each periodontal intrabony defect, the patients were monitored during 36 months for a medical exam including laboratory tests of blood and urine samples, changes in clinical attachment level, pocket depth, and linear bone growth (LBG. All three parameters improved significantly during the entire follow-up period (p<0.0001, leading to an average LBG of 4.7 mm after 36 months. Clinical mobility measured by Periotest showed a decreasing trend after the surgery. No clinical safety problems attributable to the investigational MSCs were identified. This clinical trial suggests that the stem cell therapy using MSCs-PRP/3D woven-fabric composite scaffold may constitute a novel safe and effective regenerative treatment option for periodontitis.

  20. Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer.

    Science.gov (United States)

    Khasraw, M; Pavlakis, N; McCowatt, S; Underhill, C; Begbie, S; de Souza, P; Boyce, A; Parnis, F; Lim, V; Harvie, R; Marx, G

    2010-06-01

    Docetaxel (Taxotere) improve survival and prostate-specific antigen (PSA) response rates in patients with metastatic castrate-resistant prostate cancer (CRPC). We studied the combination of PI-88, an inhibitor of angiogenesis and heparanase activity, and docetaxel in chemotherapy-naive CRPC. We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m(2) dose every three weeks Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6-99 weeks) and 1-year survival was 71%. The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile.

  1. Characterization of cellulose I/II hybrid fibers isolated from energycane bagasse during the delignification process: Morphology, crystallinity and percentage estimation.

    Science.gov (United States)

    Yue, Yiying; Han, Jingquan; Han, Guangping; Zhang, Quanguo; French, Alfred D; Wu, Qinglin

    2015-11-20

    Cellulose I, cellulose II and cellulose I/II hybrid fibers were prepared from energycane bagasse using NaOH and NaClO2 treatments. The definitive defibrillation effect with an average width of 12±5μm was observed for the fibers treated with 20wt% NaOH for 10h and NaClO2 for 2h. The ribbon shaped cellulose I fibers were converted to a swollen state with a rougher surface by 20wt% NaOH treatment for 10h. The percentage of cellulose I decreased from 100% to 5%, and the corresponding CI values increased from 58.2% to 68.8% during the conversion from cellulose I to II. After further NaClO2 treatment, the CI values were decreased because of partial destruction of hydrogen bond network. XRD, NMR and FTIR results present the same trend in the degree of crystallization for all the samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A pilot, open-label, 8-week study evaluating the efficacy, safety and tolerability of adjunctive minocycline for the treatment of bipolar I/II depression.

    Science.gov (United States)

    Soczynska, Joanna K; Kennedy, Sidney H; Alsuwaidan, Mohammad; Mansur, Rodrigo B; Li, Madeline; McAndrews, Mary Pat; Brietzke, Elisa; Woldeyohannes, Hanna O; Taylor, Valerie H; McIntyre, Roger S

    2017-05-01

    The objectives of the study were to determine if adjunctive minocycline mitigates depressive symptom severity and improves cognitive function in individuals with bipolar I/II disorder (BD). The study also aimed to determine if changes in depressive and/or cognitive symptoms over the course of treatment were associated with changes in circulating inflammatory cytokine levels. A total of 29 (intention-to-treat: n=27) adults meeting DSM-IV-TR criteria for a major depressive episode as part of bipolar I or II disorder (i.e. Hamilton Depression Rating Scale 17-item [HAMD-17] ≥20) were enrolled in an 8-week, open-label study with adjunctive minocycline (100 mg bid). The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS). The HAMD-17, Clinical Global Impression-Severity (CGI-S), cognitive test composite scores and plasma cytokines were secondary outcome measures. Plasma cytokines were measured with the 30 V-Plex Immunoassay from Meso Scale Discovery. Adjunctive minocycline was associated with a reduction in depressive symptom severity from baseline to week 8 on the MADRS (Pbipolar depression, possibly by targeting inflammatory cytokines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. La religión practicada por los militares del Ejército Romano de Hispania durante el Alto Imperio Romano (siglos I-III

    Directory of Open Access Journals (Sweden)

    Luis Sagredo San Eustaquio

    1996-01-01

    Full Text Available El estudio de !a religión practicada en las unidades del ejército romano ha sido siempre un tema que ha apasionado a los investigadores del mundo romano, disponiendo de una serie de obras generales referidas a este apartado de la vida militar durante el Imperio. Sin embargo, la religión practicada por el ejército romano acuartelado en Hispania durante el Alto imperio (siglos i-iii no ha sido, hasta el presente, analizada de una forma monográfica. La base de trabajo para poder realizar esta investigación se encuentra en los testimonios que sobre el mundo religioso proporciona la epigrafía romana de la Península, ya que son las inscripciones la fuente principal, casi única, para estudiar la religión de los militares que sirvieron en Hispania. A ellas se añaden algunos testimonios de tipo arqueológico, procedentes de las escasas e incompletas excavaciones arqueológicas de los campamentos donde estuvieron asentadas las unidades con guarnición en la Península Ibérica, fundamentalmente Petavonium (Rosinos de Vidríales, Zamora y Legio VII Gemina (León.

  4. Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study

    Directory of Open Access Journals (Sweden)

    Freihorst Joachim

    2007-08-01

    Full Text Available Abstract Background Vaccination against Pseudomonas aeruginosa is a desirable albeit challenging strategy for prevention of airway infection in patients with cystic fibrosis. We assessed the immunogenicity of a nasal vaccine based on the outer membrane proteins F and I from Pseudomonas aeruginosa in the lower airways in a phase I/II clinical trial. Methods N = 12 healthy volunteers received 2 nasal vaccinations with an OprF-OprI gel as a primary and a systemic (n = 6 or a nasal booster vaccination (n = 6. Antibodies were assessed in induced sputum (IS, bronchoalveolar lavage (BAL, and in serum. Results OprF-OprI-specific IgG and IgA antibodies were found in both BAL and IS at comparable rates, but differed in the predominant isotype. IgA antibodies in IS did not correlate to the respective serum levels. Pulmonary antibodies were detectable in all vaccinees even 1 year after the vaccination. The systemic booster group had higher IgG levels in serum. However, the nasal booster group had the better long-term response with bronchial antibodies of both isotypes. Conclusion The nasal OprF-OprI-vaccine induces a lasting antibody response at both, systemic and airway mucosal site. IS is a feasible method to non-invasively assess bronchial antibodies. A further optimization of the vaccination schedule is warranted.

  5. CD133 expression is not selective for tumor-initiating or radioresistant cell populations in the CRC cell lines HCT-116

    International Nuclear Information System (INIS)

    Dittfeld, Claudia; Dietrich, Antje; Peickert, Susann; Hering, Sandra; Baumann, Michael; Grade, Marian; Ried, Thomas; Kunz-Schughart, Leoni A.

    2009-01-01

    Background and purpose: CD133 is controversially discussed as putative (surrogate) marker for cancer stem/tumor-initiating cell populations (CSC/TIC) in epithelial tumors including colorectal carcinomas (CRCs). We studied CD133 expression in established CRC cell lines and examined in vitro behavior, radioresponse and in vivo tumor formation of CD133 +/- subpopulations of one cell line of interest. Materials and methods: Ten CRC cell lines were analyzed for CD133 expression using flow cytometry and Western blotting. CD133 + and CD133 - HCT-116 subpopulations were separated by FACS and studied in 2-D and 3-D culture and colony formation assays after irradiation. Subcutaneous xenograft formation was monitored in NMRI (nu/nu) mice. Results and conclusions: CRC cell lines could be classified into three groups: (i) CD133 - , (ii) CD133 + and (iii) those with two distinct CD133 + and CD133 - subpopulations. Isolated CD133 +/- HCT-116 subpopulations were studied relative to the original fraction. No difference was found in 2-D growth, spheroid formation or radioresponse in vitro. Also, tumor formation and growth rate did not differ for the sorted subpopulations. However, a subset of xenografts originated from CD133 - HCT-116 showed a striking enrichment in the CD133 + fraction. Our data show that CD133 expression is not selective for sphere forming, tumor-initiating or radioresistant subpopulations in the HCT-116 CRC cell lines. This implies that CD133 cannot be regarded as a CSC/TIC marker in all CRC cell lines and that functional measurements of tumor formation have to generally accompany CSC/TIC-directed mechanistic or therapeutic studies.

  6. Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin's lymphoma.

    NARCIS (Netherlands)

    Verhappen, M.H.; Poortmans, P.M.P.; Raaijmakers, E.; Raemaekers, J.M.M.

    2013-01-01

    BACKGROUND AND PURPOSE: This retrospective study investigated whether focused involved node radiation therapy (INRT) can safely replace involved field RT (IFRT) in patients with early stage aggressive NHL. PATIENTS AND METHODS: We included 258 patients with stage I/II aggressive NHL who received

  7. A structural investigation of complex I and I+III2 supercomplex from Zea mays at 11-13 angstrom resolution : Assignment of the carbonic anhydrase domain and evidence for structural heterogeneity within complex I

    NARCIS (Netherlands)

    Peters, Katrin; Dudkina, Natalya V.; Jaensch, Lothar; Braun, Hans-Peter; Boekema, Egbert J.; Jänsch, Lothar

    The projection structures of complex I and the I+III2 supercomplex from the C-4 plant Zea mays were determined by electron microscopy and single particle image analysis to a resolution of up to 11 angstrom. Maize complex I has a typical L-shape. Additionally, it has a large hydrophilic, extra-domain

  8. Erectile insufficiency as first symptom of HTLV-I/II associated myelopathy: case report Insuficiência erétil como primeiro sintoma da mielopatia associada ao HTLV I/II: relato de caso

    Directory of Open Access Journals (Sweden)

    JOSÉ TEOTONIO OLIVEIRA

    1998-03-01

    Full Text Available A case of HTLV-I/II myelopathy in which the initial complaint was erectile insufficiency (EI is reported. The only abnormalities found on the neurological exam were discrete weakness of the psoas and increased knee jerk reflexes. Diagnosis was made by demonstrating antibodies anti-HTLV I/II in the serum and cerebrospinal fluid (with the techniques of ELISA and Western blot, with confirmation by the polymerase chain reaction (PCR. EI can thus be the first symptom of HTLV-I/II infection and patients with EI of unknown etiology should be tested for HTLV-I/II in endemic areas.É relatado um caso de mielopatia associada ao HTLV I/II cuja primeira manifestação foi insuficiência erétil (IE. O exame neurológico do paciente apresentava somente discreta fraqueza dos psoas e aumento dos reflexos patelares. O diagnóstico foi feito pelo achado de anticorpos anti-HTLV I/II no soro e no líquor (com as técnicas de ELISA e Western blot e confirmado pela reação em cadeia da polimerase (PCR. Insuficiência erétil pode ser a primeira manifestação clínica de infecção pelo HTLV I/II e pacientes com IE de etiologia desconhecida devem ser testados para HTLV-I/II em áreas endêmicas.

  9. Tolko poetom hotel bõt : Rastrogannost; Dozhdlivõi den; Jaanov ogon; Setumaa I-II; Tolko poetom. Haralskije zhizneopissanija : Aire Valgus; Aare Valgus; Peeter Petrov; Vaike Metsleht; Valdur Laiapea; Hillar Aruda, ekonomist; Pärja Lumendi; Valjo Z

    Index Scriptorium Estoniae

    Traat, Mats, 1936-

    1996-01-01

    Orig.: Heldimus; Sajupäev; Jaanituli; Setumaa I-II; Ainult poeet. Harala elulood: Aire Valgus; Aare Valgus; Peeter Petrov; Vaike Metsleht; Valdur Laiapea; Hillar Aruda, ökonomist; Pärja Lumendi; Valjo Zeiger; Pavlo Moskalenko; Johannes Iva; Viljar Laanemägi; Olga Kaljusaar; Aimi Vaimets; Einard Kalm (1923-1984); Sonetid vaikimisest I; Kui

  10. The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

    International Nuclear Information System (INIS)

    Vuong, Te; Waschke, Kevin; Niazi, Tamim; Richard, Carole; Parent, Josee; Liberman, Sender; Mayrand, Serge; Loungnarath, Rasmy; Stein, Barry; Devic, Slobodan

    2011-01-01

    Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

  11. Crystal Structure of the C-terminal Region of Streptococcus mutans Antigen I/II and Characterization of Salivary Agglutinin Adherence Domains

    Energy Technology Data Exchange (ETDEWEB)

    Larson, Matthew R.; Rajashankar, Kanagalaghatta R.; Crowley, Paula J.; Kelly, Charles; Mitchell, Tim J.; Brady, L. Jeannine; Deivanayagam, Champion (King); (Cornell); (UAB); (Glasgow); (Florida)

    2012-05-29

    The Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein that adheres to salivary components and extracellular matrix molecules. Here we report the 2.5 {angstrom} resolution crystal structure of the complete C-terminal region of AgI/II. The C-terminal region is comprised of three major domains: C{sub 1}, C{sub 2}, and C{sub 3}. Each domain adopts a DE-variant IgG fold, with two {beta}-sheets whose A and F strands are linked through an intramolecular isopeptide bond. The adherence of the C-terminal AgI/II fragments to the putative tooth surface receptor salivary agglutinin (SAG), as monitored by surface plasmon resonance, indicated that the minimal region of binding was contained within the first and second DE-variant-IgG domains (C{sub 1} and C{sub 2}) of the C terminus. The minimal C-terminal region that could inhibit S. mutans adherence to SAG was also confirmed to be within the C{sub 1} and C{sub 2} domains. Competition experiments demonstrated that the C- and N-terminal regions of AgI/II adhere to distinct sites on SAG. A cleft formed at the intersection between these C{sub 1} and C{sub 2} domains bound glucose molecules from the cryo-protectant solution, revealing a putative binding site for its highly glycosylated receptor SAG. Finally, electron microscopy images confirmed the elongated structure of AgI/II and enabled building a composite tertiary model that encompasses its two distinct binding regions.

  12. A multicenter phase I/II study of obatoclax mesylate administered as a 3- or 24-hour infusion in older patients with previously untreated acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Aaron D Schimmer

    Full Text Available An open-label phase I/II study of single-agent obatoclax determined a maximum tolerated dose (MTD and schedule, safety, and efficacy in older patients (≥ 70 yr with untreated acute myeloid leukemia (AML.Phase I evaluated the safety of obatoclax infused for 3 hours on 3 consecutive days (3 h × 3 d in 2-week cycles. Initial obatoclax dose was 30 mg/day (3 h × 3 d; n = 3. Obatoclax was increased to 45 mg/day (3 h × 3 d if ≤ 1 patient had a dose-limiting toxicity (DLT and decreased to 20 mg/day (3 h × 3 d if DLT occurred in ≥ 2 patients. In the phase II study, 12 patients were randomized to receive obatoclax at the dose identified during phase I (3 h × 3 d or 60 mg/day administered by continuous infusion over 24 hours for 3 days (24 h × 3 d to determine the morphologic complete response rate.In phase I, two of three patients receiving obatoclax 30 mg/day (3 h × 3 d experienced grade 3 neurologic DLTs (confusion, ataxia, and somnolence. Obatoclax was decreased to 20 mg/day (3 h × 3 d. In phase II, no clinically relevant safety differences were observed between the 20 mg/day (3 h × 3 d; n = 7 and 60 mg/day (24 h × 3 d; n = 5 arms. Neurologic and psychiatric adverse events were most common and were generally transient and reversible. Complete response was not achieved in any patient.Obatoclax 20 mg/day was the MTD (3 h × 3 d in older patients with AML. In the schedules tested, single-agent obatoclax was not associated with an objective response. Evaluation in additional subgroups or in combination with other chemotherapy modalities may be considered for future study.ClinicalTrials.gov NCT00684918.

  13. A-Part Gel, an adhesion prophylaxis for abdominal surgery: a randomized controlled phase I-II safety study [NCT00646412].

    Science.gov (United States)

    Lang, Reinhold; Baumann, Petra; Schmoor, Claudia; Odermatt, Erich K; Wente, Moritz N; Jauch, Karl-Walter

    2015-01-01

    Intra-abdominal surgical intervention can cause the development of intra-peritoneal adhesions. To reduce this problem, different agents have been tested to minimize abdominal adhesions; however, the optimal adhesion prophylaxis has not been found so far. Therefore, the A-Part(®) Gel was developed as a barrier to diminish postsurgical adhesions; the aim of this randomized controlled study was a first evaluation of its safety and efficacy. In this prospective, controlled, randomized, patient-blinded, monocenter phase I-II study, 62 patients received either the hydrogel A-Part-Gel(®) as an anti-adhesive barrier or were untreated after primary elective median laparotomy. Primary endpoint was the occurrence of peritonitis and/or wound healing impairment 28 ± 10 days postoperatively. As secondary endpoints anastomotic leakage until 28 days after surgery, adverse events and adhesions were assessed until 3 months postoperatively. A lower rate of wound healing impairment and/or peritonitis was observed in the A-Part Gel(®) group compared to the control group: (6.5 vs. 13.8 %). The difference between the two groups was -7.3%, 90 % confidence interval [-20.1, 5.4 %]. Both treatment groups showed similar frequency of anastomotic leakage but incidence of adverse events and serious adverse events were slightly lower in the A-Part Gel(®) group compared to the control. Adhesion rates were comparable in both groups. A-Part Gel(®) is safe as an adhesion prophylaxis after abdominal wall surgery but no reduction of postoperative peritoneal adhesion could be found in comparison to the control group. This may at least in part be due to the small sample size as well as to the incomplete coverage of the incision due to the used application. NCT00646412.

  14. Revisiting dosing regimen using PK/PD modeling: the MODEL1 phase I/II trial of docetaxel plus epirubicin in metastatic breast cancer patients.

    Science.gov (United States)

    Hénin, Emilie; Meille, Christophe; Barbolosi, Dominique; You, Benoit; Guitton, Jérôme; Iliadis, Athanassios; Freyer, Gilles

    2016-04-01

    The MODEL1 trial is the first model-driven phase I/II dose-escalation study of densified docetaxel plus epirubicin administration in metastatic breast cancer patients, a regimen previously known to induce unacceptable life-threatening toxicities. The primary objective was to determine the maximum tolerated dose of this densified regimen. Study of the efficacy was a secondary objective. Her2-negative, hormone-resistant metastatic breast cancer patients were treated with escalating doses of docetaxel plus epirubicin every 2 weeks for six cycles with granulocyte colony stimulating factor support. A total of 16 patients were treated with total doses ranging from 85 to 110 mg of docetaxel plus epirubicin per cycle. Dose escalation was controlled by a non-hematological toxicity model. Dose densification was guided by a model of neutrophil kinetics, able to optimize docetaxel plus epirubicin dosing with respect to pre-defined acceptable levels of hematological toxicity while ensuring maximal efficacy. The densified treatment was safe since hematological toxicity was much lower compared to previous findings, and other adverse events were consistent with those observed with this regimen. The maximal tolerated dose was 100 mg given every 2 weeks. The response rate was 45 %; median progression-free survival was 10.4 months, whereas 54.6 months of median overall survival was achieved. The optimized docetaxel plus epirubicin dosing regimen led to fewer toxicities associated with higher efficacy as compared with standard or empirical densified dosing. This study suggests that model-driven dosage adjustment can lead to improved efficacy-toxicity balance in patients with cancer when several anticancer drugs are combined.

  15. Anti-HIV I/II activity and molecular cloning of a novel mannose/sialic acid-binding lectin from rhizome of Polygonatum cyrtonema Hua.

    Science.gov (United States)

    An, Jie; Liu, Jin-Zhi; Wu, Chuan-Fang; Li, Jian; Dai, Lei; Van Damme, Els; Balzarini, Jan; De Clercq, Erik; Chen, Fang; Bao, Jin-Ku

    2006-02-01

    The anti-human immunodeficiency virus (HIV) I/II activity of a mannose and sialic acid binding lectin isolated from rhizomes of Polygonatum cyrtonema Hua was elucidated by comparing its HIV infection inhibitory activity in MT-4 and CEM cells with that of other mannose-binding lectins (MBLs). The anti-HIV activity of Polygonatum cyrtonema Hua lectin (PCL) was 10- to 100-fold more potent than other tested MBLs, but without significant cytotoxicity towards MT-4 or CEM cells. To amplify cDNA of PCL by 3'/5'-rapid amplification of cDNA ends (RACE), the 30 amino acids of N-terminal were determined by sequencing and the degenerate oligonucleotide primers were designed. The full-length cDNA of PCL contained 693 bp with an open reading frame encoding a precursor protein of 160 amino acid residues, consisting of a 28-residue signal peptide, a 22-residue C-terminal cleavage peptide and a 110-residue mature polypeptide which contained three tandemly arranged subdomains with an obvious sequence homology to the monocot MBL. However, only one active mannose-binding site (QDNVY) was found in subdomain I of PCL, that of subdomain II and III changed to HNNVY and PDNVY, respectively. There was no intron in PCL, which was in good agreement with other monocot MBLs. Molecular modeling of PCL indicated that its three-dimensional structure resembles that of the snowdrop agglutinin. By docking, an active sialic acid-binding site was found in PCL. The instabilization of translation initiation region (TIR) in mRNA of PCL benefits its high expression in rhizomes.

  16. A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment

    International Nuclear Information System (INIS)

    Herrera, Fernanda G.; Chan, Philip; Doll, Corinne; Milosevic, Michael; Oza, Amit; Syed, Amy; Pintilie, Melania; Levin, Wilfred; Manchul, Lee; Fyles, Anthony

    2007-01-01

    Purpose: To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer. Methods and Materials: Thirty-one patients were accrued to a phase I-II trial of celecoxib 400 mg by mouth twice per day for 2 weeks before and during CRT. Tumor oxygenation (HP 5 ) and interstitial fluid pressure (IFP) were measured before and 2 weeks after celecoxib administration alone. The median follow-up time was 2.7 years (range, 1.1-4.4 years). Results: The most common acute G3/4 toxicities were hematologic (4/31, 12.9%) and gastrointestinal (5/31, 16.1%) largely attributed to chemotherapy. Late G3/4 toxicity was seen in 4 of 31 patients (13.7% actuarial risk at 2 yr), including fistulas in 3 patients (9.7%). Within the first year of follow-up, 25 of 31 patients (81%) achieved complete response (CR), of whom 20 remained in CR at last follow-up. After 2 weeks of celecoxib administration before CRT, the median IFP decreased slightly (median absolute, -4.6 mm Hg; p = 0.09; relative, -21%; p = 0.07), whereas HP 5 did not change significantly (absolute increase, 3.6%; p = 0.51; median relative increase, 11%; p = 0.27). No significant associations were seen between changes in HP 5 or IFP and response to treatment (p = 0.2, relative HP 5 change and p = 0.14, relative IFP change). Conclusions: Celecoxib in combination with definitive CRT is associated with acceptable acute toxicity, but higher than expected late complications. Celecoxib is associated with a modest reduction in the angiogenic biomarker IFP, but this does not correspond with tumor response

  17. A multicenter phase I/II study of obatoclax mesylate administered as a 3- or 24-hour infusion in older patients with previously untreated acute myeloid leukemia.

    Science.gov (United States)

    Schimmer, Aaron D; Raza, Azra; Carter, Thomas H; Claxton, David; Erba, Harry; DeAngelo, Daniel J; Tallman, Martin S; Goard, Carolyn; Borthakur, Gautam

    2014-01-01

    An open-label phase I/II study of single-agent obatoclax determined a maximum tolerated dose (MTD) and schedule, safety, and efficacy in older patients (≥ 70 yr) with untreated acute myeloid leukemia (AML). Phase I evaluated the safety of obatoclax infused for 3 hours on 3 consecutive days (3 h × 3 d) in 2-week cycles. Initial obatoclax dose was 30 mg/day (3 h × 3 d; n = 3). Obatoclax was increased to 45 mg/day (3 h × 3 d) if ≤ 1 patient had a dose-limiting toxicity (DLT) and decreased to 20 mg/day (3 h × 3 d) if DLT occurred in ≥ 2 patients. In the phase II study, 12 patients were randomized to receive obatoclax at the dose identified during phase I (3 h × 3 d) or 60 mg/day administered by continuous infusion over 24 hours for 3 days (24 h × 3 d) to determine the morphologic complete response rate. In phase I, two of three patients receiving obatoclax 30 mg/day (3 h × 3 d) experienced grade 3 neurologic DLTs (confusion, ataxia, and somnolence). Obatoclax was decreased to 20 mg/day (3 h × 3 d). In phase II, no clinically relevant safety differences were observed between the 20 mg/day (3 h × 3 d; n = 7) and 60 mg/day (24 h × 3 d; n = 5) arms. Neurologic and psychiatric adverse events were most common and were generally transient and reversible. Complete response was not achieved in any patient. Obatoclax 20 mg/day was the MTD (3 h × 3 d) in older patients with AML. In the schedules tested, single-agent obatoclax was not associated with an objective response. Evaluation in additional subgroups or in combination with other chemotherapy modalities may be considered for future study. ClinicalTrials.gov NCT00684918.

  18. Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study

    International Nuclear Information System (INIS)

    Spanos, W.J. Jr.; Wasserman, T.; Meoz, R.; Sala, J.; Kong, J.; Stetz, J.

    1987-01-01

    Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses

  19. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Directory of Open Access Journals (Sweden)

    L John Hoffer

    Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials.ClinicalTrials.gov NCT01050621.

  20. Radioimmunotherapy in medullary thyroid cancer using bispecific antibody and iodine 131-labeled bivalent hapten: preliminary results of a phase I/II clinical trial.

    Science.gov (United States)

    Kraeber-Bodéré, F; Bardet, S; Hoefnagel, C A; Vieira, M R; Vuillez, J P; Murat, A; Ferreira, T C; Bardiès, M; Ferrer, L; Resche, I; Gautherot, E; Rouvier, E; Barbet, J; Chatal, J F

    1999-10-01

    The toxicity and therapeutic efficacy of escalating doses of anti-carcinoembryonic antigen x anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid)-In bispecific monoclonal antibody (F6-734) and iodine 131-labeled bivalent hapten were determined in a Phase I/II trial. A total of 26 patients with recurrences of medullary thyroid cancer documented by imaging and a rise in serum thyrocalcitonin were enrolled. Twenty to 50 mg of F6-734 and 40-100 mCi of 131I-hapten were injected 4 days apart. Quantitative scintigraphy was performed after the second injection for dosimetry estimations in eight cases. Clinical, biological, and morphological follow-up was carried out for 1 year after treatment. The mean percentage of injected activity per gram of tumor at the time of maximum uptake was 0.08% (range, 0.003-0.26%). The tumor biological half-life ranged from 3 to 95 days, and tumor doses ranged from 2.91 to 184 cGy/mCi. The estimated tumor-to-nontumor dose ratios were 43.8 x 53.4, 29.6 x 35.3, 10.9 x 13.6, and 8.4 x 10.0 for total body, red marrow, liver, and kidney, respectively. Grade III/IV hematological toxicity was observed in seven patients, most of them with bone metastases. Among the 17 evaluable patients, 4 pain reliefs, 5 minor tumor responses, and 4 biological responses with decrease of thyrocalcitonin were observed. Nine patients developed human anti-mouse antibody. Dose-limiting toxicity was hematological, and maximum tolerated activity was 48 mCi/m2 in this group of patients, most of whom had suspected bone marrow involvement. The therapeutic responses observed in patients mainly with a small tumor burden are encouraging for the performance of a Phase II trial with minimal residual disease.

  1. Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

    International Nuclear Information System (INIS)

    Menkarios, Cathy; Fortin, Bernard; Lambert, Carole; Vigneault, Éric; Brochet, Nicolas; Nguyen, David HA; Bahary, Jean-Paul; Jolicoeur, Marjory; Beauchemin, Marie-Claude; Villeneuve, Hugo; Van Nguyen, Thu

    2011-01-01

    Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival. Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%. Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed

  2. Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Han, Ji-Youn; Lee, Soo Hyun; Lee, Geon Kook; Yun, Tak; Lee, Young Joo; Hwang, Kum Hui; Kim, Jin Young; Kim, Heung Tae

    2015-03-01

    Vorinostat has been shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated non-small cell lung cancer (NSCLC). A 3 + 3 dose-escalation design was used to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Three dose levels were tested: 250 mg/day gefitinib on days 1-28 and 200, 300 or 400 mg/day vorinostat on days 1-7, and 15-21 out of every 28 days. The primary endpoint was median progression-free survival (PFS). Fifty-two patients were enrolled and treated (43 in phase II). The median age was 59 years, 28 patients were male, 44 had adenocarcinoma, 29 had never smoked, and 36 had undergone one prior treatment. Twenty-two patients exhibited sensitive EGFR mutations. Planned dose escalation was completed without reaching the MTD. The RP2D was 250 mg gefitinib and 400 mg vorinostat. In 43 assessable patients in phase II, the median PFS was 3.2 months; the overall survival (OS) was 19.0 months. There were 16 partial responses and six cases of stable disease. In EGFR-mutant NSCLC, response rate was 77 %, median PFS was 9.1 months, and median OS was 24.1 months. The most common adverse events were anorexia and diarrhea. Treatment with 250 mg gefitinib daily with biweekly 400 mg/day vorinostat was feasible and well tolerated. In an unselected patient population, this combination dose did not improve PFS. However, this combination showed a potential for improving efficacy of gefitinib in EGFR-mutant NSCLC (NCT01027676).

  3. Manuscript title: Disrupting cytokine signaling in pancreatic cancer: A phase I/II study of Etanercept in combination with Gemcitabine in patients with advanced disease

    Science.gov (United States)

    Wu, C; Fernandez, SA; Criswell, T; Chidiac, T; Guttridge, D; Villalona-Calero, M; Bekaii-Saab, T

    2012-01-01

    Objectives Etanercept blocks tumor necrosis factor-α (TNF), a proinflammatory cytokine that plays a role in cancer-related cachexia and tumor growth. A phase I/II study was conducted to assess the tolerability and efficacy of gemcitabine and etanercept in advanced pancreatic cancer. Methods Twenty-five patients received etanercept 25mg subcutaneously twice-weekly with gemcitabine. A control cohort of 8 patients received gemcitabine alone. The primary end-point was progression-free survival (PFS) at 6 months. Blood specimens were analyzed for TNF, IL-1b, IL-6, interferon-γ, IL-10, and NF-kB activation. The trial is registered with ClinicalTrials.gov, number NCT00201838. Results Thirty-eight patients participated in this study. In the gemcitabine-etanercept cohort, grade 3/4 drug-related toxicities included leucopenia (3) and neutropenia (6). There were 3 (12%) patients with partial response and 8 (32%) patients with stable disease. The rate of PFS at 6 months was 28% (n=7; 95% CI 20–36%). Median time to progression was 2.23 months (95% CI, 1.86–4.36 months) and median overall survival was 5.43 months (95% CI, 3.30–10.23 months). Clinical benefit rate was 33% of the evaluable patients. A correlation was seen between IL-10 levels and clinical benefit. Conclusions Etanercept added to gemcitabine is safe but did not show significant enhancement of gemcitabine in patients with advanced pancreatic cancer. PMID:23429495

  4. Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

    OpenAIRE

    Murphy, Caitlin C.; Sanoff, Hanna K.; Stitzenberg, Karyn B.; Baron, John A.; Lund, Jennifer L.; Sandler, Robert S.

    2017-01-01

    Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n = 6, 862). Tumor characteristics...

  5. The catabolite repression control protein Crc plays a role in the development of antimicrobial-tolerant subpopulations in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Zhang, Lianbo; Chiang, Wen-Chi; Gao, Qingguo

    2012-01-01

    Bacteria form complex surface-attached biofilm communities in nature. Biofilm cells differentiate into subpopulations which display tolerance towards antimicrobial agents. However, the signal transduction pathways regulating subpopulation differentiation in biofilms are largely unelucidated....... In the present study, we show that the catabolite repression control protein Crc regulates the metabolic state of Pseudomonas aeruginosa cells in biofilms, and plays an important role in the development of antimicrobial-tolerant subpopulations in P. aeruginosa biofilms....

  6. Predicting Outcome and Therapy Response in mCRC Patients Using an Indirect Method for CTCs Detection by a Multigene Expression Panel: A Multicentric Prospective Validation Study

    Directory of Open Access Journals (Sweden)

    Yolanda Vidal Insua

    2017-06-01

    Full Text Available Colorectal cancer (CRC is one of the major causes of cancer-related deaths. Early detection of tumor relapse is crucial for determining the most appropriate therapeutic management. In clinical practice, computed tomography (CT is routinely used, but small tumor changes are difficult to visualize, and reliable blood-based prognostic and monitoring biomarkers are urgently needed. The aim of this study was to prospectively validate a gene expression panel (composed of GAPDH, VIL1, CLU, TIMP1, TLN1, LOXL3 and ZEB2 for detecting circulating tumor cells (CTCs as prognostic and predictive tool in blood samples from 94 metastatic CRC (mCRC patients. Patients with higher gene panel expression before treatment had a reduced progression-free survival (PFS and overall-survival (OS rates compared with patients with low expression (p = 0.003 and p ≤ 0.001, respectively. Patients with increased expression of CTCs markers during treatment presented PFS and OS times of 8.95 and 11.74 months, respectively, compared with 14.41 and 24.7 for patients presenting decreased expression (PFS; p = 0.020; OS; p ≤ 0.001. Patients classified as non-responders by CTCs with treatment, but classified as responders by CT scan, showed significantly shorter survival times (PFS: 8.53 vs. 11.70; OS: 10.37 vs. 24.13; months. In conclusion, our CTCs detection panel demonstrated efficacy for early treatment response assessment in mCRC patients, and with increased reliability compared to CT scan.

  7. Anti-wear properties of Cr-C and Ni-Co alloy coatings as substitutes for conventional nanocrystalline Cr coatings

    International Nuclear Information System (INIS)

    Zeng Zhixiang; Zhang Junyan

    2008-01-01

    Nanocrystalline Ni-Co, amorphous Cr-C alloy and nanocrystalline Cr-C coatings were electrodeposited from 'environmentally acceptable' electrolytes as potential substitutes for conventional nanocrystalline Cr coatings electrodeposited from noxious hexavalent chromium. The structure, morphology and hardness of coatings are investigated using a transmission electron microscope, a scanning electronic microscope and a Vickers hardness tester, respectively. Anti-wear properties are tested on a pin-on-plate vibrant wear tester. The correlation between the wear resistance, hardness, brittleness and the lubricated state is investigated. The results show that the wear behaviour of specimens significantly depends on their lubricated state, hardness and brittleness. Under the lubricated sliding condition, abrasive wear is the primary wear mechanism for all specimens. With respect to the abrasive wear mechanism, both the elastic and plastic deformations play important roles during the lubricated sliding process. Thus, the amorphous and nanocrystalline Cr-C alloy coatings, with both high brittleness and high hardness, exhibit a lower wear rate than the conventional Cr and Ni-Co coatings. On the other hand, under the dry sliding condition, the annealed Ni-Co coating, with an excellent compromise between high hardness and toughness, exhibits an abrasive wear mechanism and a relatively low wear rate; in contrast, the brittle Cr-matrix coatings exhibit a severe fatigue/delamination wear mechanism and high wear rate

  8. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer.

    Science.gov (United States)

    Podrazil, Michal; Horvath, Rudolf; Becht, Etienne; Rozkova, Daniela; Bilkova, Pavla; Sochorova, Klara; Hromadkova, Hana; Kayserova, Jana; Vavrova, Katerina; Lastovicka, Jan; Vrabcova, Petra; Kubackova, Katerina; Gasova, Zdenka; Jarolim, Ladislav; Babjuk, Marek; Spisek, Radek; Bartunkova, Jirina; Fucikova, Jitka

    2015-07-20

    We conducted an open-label, single-arm Phase I/II clinical trial in metastatic CRPC (mCRPC) patients eligible for docetaxel combined with treatment with autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa). The primary and secondary endpoints were safety and immune responses, respectively. Overall survival (OS), followed as a part of the safety evaluation, was compared to the predicted OS according to the Halabi and MSKCC nomograms. Twenty-five patients with progressive mCRPC were enrolled. Treatment comprised of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 107 dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis. No serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13-0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17-0.63) predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS. In patients with mCRPC, the combined chemoimmunotherapy with DCVAC/PCa and docetaxel was safe and resulted in longer than expected survival. Concomitant chemotherapy did not preclude the induction of specific anti-tumor cytotoxic T cells.

  9. Combination therapy of renal cell carcinoma or breast cancer patients with dendritic cell vaccine and IL-2: results from a phase I/II trial

    Directory of Open Access Journals (Sweden)

    Kim YongMan

    2011-10-01

    Full Text Available Abstract Background Ten cancer patients (Six renal cell carcinoma and four breast cancer patients were treated in a phase I/II study with a vaccine composed of autologous dendritic cells (DCs and IL-2 to evaluate the DC vaccine-related toxicity and antigen-specific immune alteration. Methods Cancer patients were treated twice with autologous CD34+ hematopoietic stem cell-derived, GM-CSF/IFN-γ-differentiated DCs pulsed with autologous tumor lysate and KLH, by 4-week interval. Following each subcutaneous injection of therapeutic DCs, low-dose (200 MIU IL-2 was introduced for 14 consecutive days as an immune adjuvant. To determine the DC vaccine-induced immunological alterations, the KLH-specific lymphocyte proliferation, number of IFN-γ secreting T cells (ELISPOT assay, NK activity and the cytokine modulation were measured. Results Cultured-DCs expressing HLA-DR, CD11c, CD83, and B7.1/B7.2 produced IL-12p70. After vaccination, the patients tolerated it. Clinical response was observed in one RCC patient as stable disease. However DC-vaccine related antigen-specific immune responses including peripheral blood lymphocyte proliferation and the number of IFN-r secreting cells were induced in six patients without clear correlation with clinical responses. Also NK activity was induced significantly in six patients after vaccination. DC vaccine-related decrease of TGF-β level or increase of IL-12p70 level and decline of CD4+CD25+ T cells were observed in three patients. However only in the RCC patient whose disease stabilized, combination of stimulatory as well as inhibitory immune alterations including induction of IFN-γ secreting T cell with reduction of CD4+ CD25+ T cell were correlated with clinical responses. Conclusion Data indicated that DC vaccine combined with IL-2 is well tolerated without major side effects. DC vaccine induced the specific immunity against introduced antigen. Combinatorial alterations of immunological parameters indicating antigen-specific immune induction along with reduction of inhibitory immunity were correlated with clinical responses in DC vaccine treated patients.

  10. Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

    Energy Technology Data Exchange (ETDEWEB)

    Kankaanranta, Leena [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Seppaelae, Tiina; Koivunoro, Hanna [Department of Physics, University of Helsinki, Helsinki (Finland); Boneca Corporation, Helsinki (Finland); Saarilahti, Kauko [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Atula, Timo [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Collan, Juhani [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Salli, Eero; Kortesniemi, Mika [Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Uusi-Simola, Jouni [Department of Physics, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Vaelimaeki, Petteri [Department of Physics, University of Helsinki, Helsinki (Finland); Boneca Corporation, Helsinki (Finland); Maekitie, Antti [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Seppaenen, Marko [Turku PET Centre, Turku University Hospital, Turku (Finland); Minn, Heikki [Department of Oncology, Turku University Central Hospital, Turku (Finland); Revitzer, Hannu [Aalto University School of Science and Technology, Esopo (Finland); Kouri, Mauri [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro [VTT Technical Research Centre of Finland, Espoo (Finland); Savolainen, Sauli [Department of Physics, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Joensuu, Heikki, E-mail: heikki.joensuu@hus.fi [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland)

    2012-01-01

    Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by use of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was acceptable. Further research on novel modifications of the method is warranted.

  11. Results of a phase I-II study on intraductal confocal microscopy (IDCM) in patients with common bile duct (CBD) stenosis.

    Science.gov (United States)

    Giovannini, M; Bories, E; Monges, G; Pesenti, C; Caillol, F; Delpero, J R

    2011-07-01

    Confocal endomicroscopy is an emergent technique and allows real optical biopsies in the gastrointestinal (GI) tract. The aim of this study was to evaluate a new intraductal confocal miniprobe in patients with a normal common bile duct (CBD) or with a suspicion of a malignant stenosis (cholangiocarcinoma). Thirty-seven patients (23 males) underwent endoscopic retrograde cholangiopancreatography (ERCP) for bile duct stone removal (7 cases) or bile duct stenosis (30 cases). Intraductal confocal microscopy (IDCM) was performed during the ERCP using a probe-based confocal laser endomicroscopy (pCLE) technique. IDCM was done with the CholangioFlex probe with Cellvizio (Mauna Kea Technologies, Paris, France). The depth of penetration of theCholangioFlex probe was 40-70 μm and magnification was 400×. Images were reviewed by an experienced pathologist in GI disease and compared to ERCP findings, CBD biopsies performed during ERCP or EUS, and in 15 patients to the resected specimen (Wipple resection). No complications related to the CholangioFlex insertion occurred after the ERCP. Good images were obtained in 33 patients. Final histology diagnosis was a normal CBD in 7 cases, 23 malignant stenoses (4 ampullary carcinomas, 13 cholangiocarcinomas, and 6 pancreatic cancer), and 7 inflammatory stenoses (4 chronic pancreatitis, 1 stenosis of hepaticojejunal anastomosis, 1 postcholecystectomy CBD stenosis, and 1 primary sclerosing cholangitis). IDCM of a normal CBD showed a thin black band (CBD wall, large black band (>20 μm), and an aggregate of irregular black cells (black clumps). These aspects were seen in all malignant stenoses and none were seen in benign or normal CBD. The presence of irregular vessels, large black bands, and black clumps seen with confocal laser microscopy enabled prediction of neoplasia with an accuracy rate of 86%, sensitivity of 83%, and specificity of 75%. The respective numbers for standard histopathology were 53, 65, and 53%. This phase I-II study on IDCM showed that IDCM is feasible. This new technique will open a new door for optical biopsy of the CBD.

  12. Associations of Census-Tract Poverty with Subsite-Specific Colorectal Cancer Incidence Rates and Stage of Disease at Diagnosis in the United States

    Directory of Open Access Journals (Sweden)

    Kevin A. Henry

    2014-01-01

    Full Text Available Background. It remains unclear whether neighborhood poverty contributes to differences in subsite-specific colorectal cancer (CRC incidence. We examined associations between census-tract poverty and CRC incidence and stage by anatomic subsite and race/ethnicity. Methods. CRC cases diagnosed between 2005 and 2009 from 15 states and Los Angeles County (N=278,097 were assigned to 1 of 4 groups based on census-tract poverty. Age-adjusted and stage-specific CRC incidence rates (IRs and incidence rate ratios (IRRs were calculated. Analyses were stratified by subsite (proximal, distal, and rectum, sex, race/ethnicity, and poverty. Results. Compared to the lowest poverty areas, CRC IRs were significantly higher in the most impoverished areas for men (IRR = 1.14 95% CI 1.12–1.17 and women (IRR = 1.06 95% CI 1.05–1.08. Rate differences between high and low poverty were strongest for distal colon (male IRR = 1.24 95% CI 1.20–1.28; female IRR = 1.14 95% CI 1.10–1.18 and weakest for proximal colon. These rate differences were significant for non-Hispanic whites and blacks and for Asian/Pacific Islander men. Inverse associations between poverty and IRs of all CRC and proximal colon were found for Hispanics. Late-to-early stage CRC IRRs increased monotonically with increasing poverty for all race/ethnicity groups. Conclusion. There are differences in subsite-specific CRC incidence by poverty, but associations were moderated by race/ethnicity.

  13. Comparing the effect of An's Shaobei Injection ([symbols; see text]) with Xiaozhiling Injection ([symbols; see text]) in patients with internal hemorrhoids of grade I-III: a prospective cohort study.

    Science.gov (United States)

    An, A-yue; Feng, Da-yong; Wang, Chun-hui; Shi, Yu-ying; Xiang, Jing-jing; Bai, Zhi-yong; Li, Kun-cheng; Liu, Jin-yang

    2014-07-01

    To compare the effect of An's Shaobei Injection ([symbols; see text]) with Xiaozhiling Injection ([symbols; see text]) in patients with internal hemorrhoids of grade I-III. This cohort study included 1,520 internal hemorrhoids patients with grade I-III who were scheduled for liquid injection treatment from July 2003 to July 2009. The cohort included patients who underwent either An's Shaobei Injection treatment (the treatment group, 760 cases) or Xiaozhiling Injection treatment (the control group, 760 cases). All patients were followed up regularly for 3 years; the observing indices included anal function recovery and clinical response after operation. Among the 1,520 patients, 1,508 (99.2%) completed the 3-year follow-up. The efficacy rate was 97.5% in the treatment group, significantly higher than the control group (91.8%, Peffect to Xiaozhiling Injection with fewer adverse effects.

  14. Treatment of advanced colorectal cancer (CRC) in daily practice: results of a survey in two Italian regions, Piemonte and Valle d'Aosta.

    Science.gov (United States)

    Comandone, A; Berardo, R; Faggiuolo, R; Boglione, A; Bergnolo, P; Dal Canton, O; Di Napoli, A; Oliva, C; Bumma, C

    1998-01-01

    Colorectal cancer (CRC) is one of the most important health problems in Western countries: it is the fourth cancer in terms of incidence and the second cause of cancer death. Surgery is the main therapeutic choice and there is broad consensus on the role of adjuvant chemotherapy (CT) after resection. Unfortunately, 50% of the patients will relapse and die of the disease. Palliative CT based on 5-fluorouracil (5FU) may induce a 9-48% response rate with a median survival of 11.5 months. At present there is no gold standard for CT In advanced CRC and the situation has become more complicated since the advent of new drugs (Raltitrexed, Irinotecan, Oxaliplatin). The aim of this study was the identification of the different approaches to treatment of advanced CRC among the clinicians (oncologists, radiologists, internal medicine specialists, surgeons) who practice CT. Forty-six clinicians from two Italian Regions (Piemonte and Valle d'Aosta) were interviewed by telephone. 5FU modulated with Lederfolin according to the classic Machover scheme is the main option in daily practice. More sophisticated therapies are reserved to patients with a good performance status (PS) and are prescribed only in the larger centers. The planned therapies usually consist of six courses. Restaging may be performed after three or six courses. A marked difference has been recorded in the evaluation of a situation of no change (NC): 25.5% of the clinicians evaluate stable disease as a positive result. In the event of disease progression or relapse, 35% of the clinicians do not prescribe second-line CT. In case of further treatment, the options are totally subjective. A national survey on this issue is necessary under the auspices of AIOM (Associazione Italiana Oncologia Medica) and involving oncologists, epidemiologists and statisticians, in order to define the reasons for variations in therapy in advanced CRC and determine the differences between clinicians of different age, specialization and

  15. Changes in soluble CEA and TIMP-1 levels during adjuvant chemotherapy for stage III colon cancer

    DEFF Research Database (Denmark)

    Aldulaymi, Bahir; Christensen, Ib Jarle; Sölétormos, György

    2010-01-01

    Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antige...... (CEA) levels in patients with stage III colon cancer.......Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antigen...

  16. Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages.

    Science.gov (United States)

    Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

    2014-12-28

    To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC.

  17. A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid in Advanced Sarcomas

    Directory of Open Access Journals (Sweden)

    Varun Monga

    2018-02-01

    Full Text Available Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical trials, but most of the findings have not supported its use. We hypothesized the existence of an epigenetically mediated “angiogenic switch”, and the tumor microenvironment, prevents bevacizumab from truly blocking angiogenesis. The addition of valproic acid (VPA, a weak histone deacetylase inhibitor, and bevacizumab, a monoclonal antibody against vascular endothelial growth factor, together with the cytotoxic effects of gemcitabine and docetaxel, may enhance responses and alter chemoresistance. This was designed as a phase I/II trial with primary endpoints including safety of the treatment combination and tumor response. Unresectable or metastatic sarcoma patients >18 years of age, irrespective of number of prior treatments, received VPA 40 mg/kg orally for 5 days prior to day 1, bevacizumab at 15 mg/kg IV on day 1, gemcitabine 900 mg/m2 (day 1, day 8, and docetaxel 75 mg/m2 (day 8. Cycles were of 28 day duration. Bevacizumab and VPA were continued as maintenance after 6 cycles, until disease progression. A standard 3 + 3 phase I dose de-escalation design was utilized to evaluate safety. Gain of function p53 gene mutation testing was performed on available archival tissue specimens. A total of 46 patients (30 female, 16 male with median age of 60 (range 24–81 years were enrolled; 34 (73.9% patients received prior chemotherapy, 14 (30% of which received prior gemcitabine and docetaxel. Patients received a median of 5.5 cycles (range 0–24 of treatment (min 0, one patient died prior to completing the first cycle; max: 24, one patient received 6 cycles and 18 maintenance cycles before progressing. Seventeen patients underwent dose reduction, of which VPA was reduced in 6 patients. Forty-one patients were evaluable for response. There was a confirmed complete response in 1 (epithelioid sarcoma, and a partial response (PR in 6 (1 carcinosarcoma, 2 extrauterine leiomyosarcoma (LMS, 2 undifferentiated pleomorphic sarcoma, and 1 uterine LMS patients. Stable disease (SD was seen in 21 patients for at least 2 months. One subject with prior gemcitabine and docetaxel had PR, and 7 had SD. Median progression-free survival (PFS was 5.7 months (95% CI: 2.1–8.0, and overall survival (OS was 12.9 months (95% CI: 8.3–14.5. Three patients died due to tumor progression while on the study. The combination of VPA, bevacizumab, gemcitabine, and docetaxel appears to be moderately safe and well tolerated. Given that there are very limited options for patients with relapsed refractory STS, this drug combination may be an important therapy to consider. This combination treatment deserves further investigation in epithelioid and carcinosarcoma subtypes.

  18. Stage design

    International Nuclear Information System (INIS)

    Shacter, J.

    1975-01-01

    A method is described of cycling gases through a plurality of diffusion stages comprising the steps of admitting the diffused gases from a first diffusion stage into an axial compressor, simultaneously admitting the undiffused gases from a second diffusion stage into an intermediate pressure zone of said compressor corresponding in pressure to the pressure of said undiffused gases, and then admitting the resulting compressed mixture of diffused and undiffused gases into a third diffusion stage

  19. Double immunohistochemistry enhances detection of lymphatic and venous invasion in early-stage colorectal cancer.

    Science.gov (United States)

    Ervine, A J; McBride, H A; Kelly, P J; Loughrey, M B

    2015-09-01

    Lymphatic invasion (LI) and venous invasion (VI) are regarded as important risk factors of nodal disease in early-stage colorectal cancer (CRC) but with variable reporting and poor distinction of these parameters in previous studies. This study examines the application of a double immunohistochemistry (D-IHC) method to help detect and distinguish LI and VI, in comparison with haematoxylin and eosin (H&E) staining, in a clinical series of cases of stage pT1 CRC. The aims were to demonstrate feasibility of this methodology in routine practice and compare rates of LI and VI reporting with and without D-IHC application. D-IHC utilising CAM5.2 with the endothelial marker CD34 and with the specific lymphatic endothelial marker D2-40 was performed on parallel sections from single representative paraffin tissue blocks in 28 cases of stage pT1 CRC from routine clinical practice. D-IHC significantly increased rates of both LI and VI reporting, from 14.3 to 35.7 % and from 14.3 to 28.6 %, respectively. The D-IHC methodology described is technically feasible in routine practice and potentially offers a more sensitive and robust assay for detection and distinction of LI and VI in early CRC pathology reporting. The reproducibility and clinical significance of enhanced LI and VI detection by this method and the relative importance of LI and VI in this clinical setting require further study.

  20. Prognostic significance of gene amplification of ACTN4 in stage I and II oral tongue cancer.

    Science.gov (United States)

    Kakuya, T; Mori, T; Yoshimoto, S; Watabe, Y; Miura, N; Shoji, H; Onidani, K; Shibahara, T; Honda, K

    2017-08-01

    Despite complete resection of the early stage of oral tongue cancer by partial glossectomy, late cervical lymph node metastasis is frequently observed. Gene amplification of ACTN4 (protein name: actinin-4) is closely associated with the metastatic potential of various cancers. This retrospective study was performed to demonstrate the potential usefulness of ACTN4 gene amplification as a prognostic biomarker in patients with stage I/II oral tongue cancer. Fifty-four patients with stage I/II oral tongue cancer were enrolled retrospectively, in accordance with the reporting recommendations for tumour marker prognostic studies (REMARK) guidelines. The copy number of ACTN4 and the protein expression of actinin-4 were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. The overall survival time of patients with gene amplification of ACTN4 was significantly shorter than that of patients without gene amplification (P=0.0010, log-rank test). Gene amplification of ACTN4 was a significant independent risk factor for death in patients with stage I/II oral tongue cancer (hazard ratio 6.08, 95% confidence interval 1.66-22.27). Gene amplification of ACTN4 is a potential prognostic biomarker for overall survival in oral tongue cancer. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. BRAFV600E mutation analysis in patients with metastatic colorectal cancer (mCRC in daily clinical practice: correlations with clinical characteristics, and its impact on patients' outcome.

    Directory of Open Access Journals (Sweden)

    Zacharenia Saridaki

    Full Text Available To prospectively evaluate the usefulness of the BRAFV600E mutation detection in daily clinical practice in patients with metastatic Colorectal Cancer (mCRC.504 mCRC patients treated with systemic chemotherapy ± biologics were analyzed.A statistically significant higher incidence of the BRAF mutation was observed in patients with ECOG-PS 2 (p=0.001, multiple metastatic sites (p=0.002,> 65 years old (p=0.004, primary tumors located in the colon (p<0.001, high-grade tumors (p=0.001 and in those with mucinous features (p=0.037. Patients with BRAFV600E mutated tumors had a statistically significantly reduced progression-free survival (PFS compared to wild-type (wt ones (4.1 and 11.6 months, respectively; p<0.001 and overall survival (OS (14.0 vs. 34.6 months, respectively; p<0.001. In the multivariate analysis the BRAFV600E mutation emerged as an independent factor associated with reduced PFS (HR: 4.1, 95% CI 2.7-6.2; p<0.001 and OS (HR: 5.9, 95% CI 3.7-9.5; p<0.001. Among the 273 patients treated with salvage cetuximab or panitumumab, the BRAFV600E mutation was correlated with reduced PFS (2.2 vs. 6.0 months; p<0.0001 and OS (4.3 vs. 17.4 months; p<0.0001.The presence of BRAFV600E-mutation in mCRC characterizes a subgroup of patients with distinct biologic, clinical and pathological features and is associated with very poor patients' prognosis.

  2. Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems

    Directory of Open Access Journals (Sweden)

    Rowe Krista L

    2008-11-01

    Full Text Available Abstract Background Stage at diagnosis plays a significant role in colorectal cancer (CRC survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. Methods Two distinct healthcare populations in the United States (US were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA hospitals from 2003–2007. We assessed metastatic CRC patients treated from 2003–2006 at 10 non-VA, fee-for-service (FFS practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic. Race was dichotomized (white, non-white. Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. Results 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77% reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD age 67 (11, Charlson index 2.0 (1.0, and were 63% white. FFS patients were mean age 61 (13, Charlson index 1.6 (1.0, and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR 0.76, 95% confidence interval (CI 0.58–1.00; p = 0.045; no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82–1.44; p = 0.57. In both cohorts, no association was found between stage at diagnosis and either age or race. Conclusion Higher comorbidity may lead to

  3. EFECTO DE LA ADICIÓN DE CARRAGENINA KAPPA I.II Y GOMA TARA SOBRE CARACTERÍSTICAS DE CALIDAD DEL JAMÓN DE CERDO PICADO Y COCIDO EFFECT OF THE ADDITION OF KAPPA I.II CARRAGEENAN AND TARA GUM ON QUALITY CHARACTERISTICS OF COOKED AND CHOPPED PORK HAMS

    Directory of Open Access Journals (Sweden)

    Diego Alonso Restrepo Molina

    2010-12-01

    Full Text Available Se evaluaron sinéresis, color y dureza instrumental y, sensorialmente las características de olor, sabor, color y dureza en jamones inyectados, cocidos y picados de cerdo, los cuales se habían elaborado aplicando en la salmuera de inyección una mezcla de hidrocoloides compuesta por carragenina kappa I.II y goma tara en una proporción de 79:21, en niveles del 1% y 1,2%, usando tres repeticiones para el estudio. Los jamones así elaborados se compararon contra un jamón testigo, elaborado sin el uso de estos hidrocoloides. Los valores obtenidos para los atributos, se analizaron mediante un diseño de una sola vía, con 5 repeticiones en el tiempo (0, 10, 20, 28 y 34 días, dando un arreglo factorial. Los resultados muestran que el tratamiento 2 (1,2% presentó la menor liberación de agua y la mayor dureza. No se registró diferencia entre los tratamientos y el testigo para la característica elasticidad. El testigo mostró las mejores características de color, olor y sabor sensoriales. La edad influyó en las características dureza y sinéresis en forma determinante, señalando el período desde el día 15 hasta el día 28 como aquel en que más se agudiza la sinéresis, siendo ésta más notable en el testigo que no contenía hidrocoloide.Characteristics of quality, color, texture and sineresis (instrumental and, odor, flavor, color and hardness (sensory of injected, cooked and chopped pork hams were assessed, which were manufactured using a mix of hydrocolloids in the brine of injection comprised by kappa I.II carrageenan and tara gum in a 79:21 ratio, at levels of 1% and 1.2%, using three replicates for the study; the finished hams were compared with a control ham, manufactured without the use of these hydrocolloids. The values obtained for the attributes, were analyzed through a one way design, with 5 repetitions in time (0, 10, 20, 28 and 34 days, providing a factorial arrangement. The results showed that the treatment 2 (1.2% presented the lower water release and the higher hardness. It showed no significant difference between the treatments and the control for the characteristic of elasticity. The control showed the best sensory characteristics of color, odor, and taste. The age strongly influenced in the characteristics of hardness and sineresys, defining the time from the day 15 to the 28, as the period with the highest sneresys, most noticeable in the control with no hydrocolloid addtion.

  4. Treatment-related upper-limb morbidity one year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for stage I or II breast cancer

    NARCIS (Netherlands)

    Rietman, J.S.; Dijkstra, P.U.; Geertzen, J.H.; Baas, P.; de Vries, J; Dolsma, W.; Groothoff, J.W.; Eisma, W.H.; Hoekstra, H.J.

    BACKGROUND: In a prospective study, upper limb morbidity and perceived disability/activities of daily life (ADLs) were assessed before and 1 year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). METHODS: A total of 204 patients with stage I/II breast cancer (mean

  5. Treatment-related upper limb morbidity 1 year after sentinel lymph node biopsy or axillary lymph node dissection for stage I or II breast cancer

    NARCIS (Netherlands)

    Rietman, J.S.; Dijkstra, P.U.; Geertzen, J.H.B.; Baas, P.; de Vries, J; Dolsma, W.V.; Groothoff, J.W.; Eisma, W.H.; Hoekstra, H.J

    2004-01-01

    Background: In a prospective study, upper limb morbidity and perceived disability/activities of daily life (ADLs) were assessed before and 1 year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Methods: A total of 204 patients with stage I/II breast cancer (mean

  6. Prognostic implications of occult nodal tumour cells in stage I and II colon cancer: The correlation between micrometastasis and disease recurrence

    NARCIS (Netherlands)

    Sloothaak, D. A. M.; van der Linden, R. L. A.; van de Velde, C. J. H.; Bemelman, W. A.; Lips, D. J.; van der Linden, J. C.; Doornewaard, H.; Tanis, P. J.; Bosscha, K.; van der Zaag, E. S.; Buskens, C. J.

    2017-01-01

    Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer. The objective of this retrospective multicenter study

  7. Trading stages

    DEFF Research Database (Denmark)

    Steiner, Uli; Tuljapurkar, Shripad; Coulson, Tim

    2012-01-01

    because they are hard to use and interpret, and tools for age and stage structured populations are missing. We present easily interpretable expressions for the sensitivities and elasticities of life expectancy to vital rates in age-stage models, and illustrate their application with two biological......Interest in stage-and age structured models has recently increased because they can describe quantitative traits such as size that are left out of age-only demography. Available methods for the analysis of effects of vital rates on lifespan in stage-structured models have not been widely applied...... examples. Much of our approach relies on trading of time and mortality risk in one stage for time and risk in others. Our approach contributes to the new framework of the study of age- and stage-structured biodemography....

  8. Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

    Science.gov (United States)

    Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

    2017-07-01

    Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Low folate metabolic stress reprograms DNA methylation-activated sonic hedgehog signaling to mediate cancer stem cell-like signatures and invasive tumour stage-specific malignancy of human colorectal cancers.

    Science.gov (United States)

    Feng, Hsin-Chun; Lin, Jhuan-Yu; Hsu, Shu-Han; Lan, Wen-Yu; Kuo, Chang-Sheng; Tian, Yu-Feng; Sun, Ding-Ping; Huang, Rwei-Fen Syu

    2017-12-15

    The mechanistic role of colonic low folate metabolic stress (LFMS) in colorectal cancer (CRC) malignancy development remains unknown. Folate analysis on the 99 paired human CRC tissues localized LFMS to the deep invasive T3/T4 staged tumours with hypo-methylated sonic hedgehog (Shh) promoter region and amplified expressions of Shh ligand and Gli1 effector, which coincided with deregulated expressions of the epithelial-mesenchymal transition (EMT) mediators. Colonic folate levels of CRC were inversely correlated with pluripotent expressions of the SOX2, NANOG and OCT4 markers (p cells to LFMS microenvironment significantly hypomethylated Shh promoter region, activated Shh signaling, induced transcript and protein expressions of the pluripotent markers, promoted trans-differentiation as EMT by deregulation of Snail mediator and epithelial marker E-cadherin, increased MMP2/MMP9 enzymatic digestion on matrix protein for invasion, and promoted self-renewal capability of anchorage-independent tumor-spheroid formation. LFMS-induced cancer stem cell (CSC) signature and CRC invasion is synergized with inhibition of DNA methylation by 5-Aza-2-deoxycytidine (5AZA) in rewiring EMT genotypes, which can be blockade by the Shh inhibitor (cyclopamine). The in vivo and in vitro data corroboratively identify CSC-like molecular targets specific to the LFMS-predisposed invasive CRC through reprogramming DNA methylation-activated Shh signaling. The study highlights CSC targets specific to LFMS-predisposed invasive CRC in optimizing folate co-chemotherapy to minimize tumour metastasis potential of CRC patients. © 2017 UICC.

  10. Precision and accuracy control of dose calibrator: CAPINTEC CRC 12 in laboratory for radiopharmacy of Nuclear Medicine Institute of Sucre, Bolivia

    International Nuclear Information System (INIS)

    Huanca Sardinas, E; Castro Sacci, O; Torrez Cabero, M; Vasquez Ibanez, M.R; Zambrana Zelada, AJ.

    2013-01-01

    The dose calibrator is one of the indispensable tools in radiopharmacy laboratories of a nuclear medicine department also is mandated to provide accurate readings. A very high doses produce unnecessary radiation exposure to the patient or a very low dose, prolong the acquisition time of the studies affecting the quality of the image. In the present work we did a retrospective analysis of the results of quality checks performed at precision accuracy of the Gauge CRC12 CAPINTEC dose calibrator over a period of 16 years, using sealed certified sources with low power, medium and high: Ba 133 , Cs 137 , Co 60 and Co 57 . The results showed that the lowest standard deviation value was 0.17 for Ba133, relative to Co 57 of 2.97 in the control of accuracy. Accuracy over control values were also lower standard deviation for Ba 133 1.00, relative to Co 57 10.06. Being stated that the CRC12 CAPINTEC activimeter reliability is acceptable during the reporting period and under the conditions indicated. Therefore, we continue to make these quality control procedures and the professional must feel confident that the measurements obtained with it are reliable

  11. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I-III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue.

    Science.gov (United States)

    Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

    2016-01-01

    This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t 0) and after the intervention (t 1) as well as 3 months after finishing intervention (t 2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t 0 to t 2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t 0 to t 1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t 1 and t 2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t 1 nor for t 2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase.

  12. Quality assurance of EORTC trial 22922/10925 investigating the role of internal mammary--medial supraclavicular irradiation in stage I-III breast cancer: the individual case review

    NARCIS (Netherlands)

    Poortmans, P.; Kouloulias, V. E.; Venselaar, J. L.; Struikmans, H.; Davis, J. B.; Huyskens, D.; van Tienhoven, G.; Hurkmans, C.; Mijnheer, B.; van den Bogaert, W.

    2003-01-01

    To assess consistency among participants in an European Organisation for Research and Treatment of Cancer (EORTC) phase III trial randomising between irradiation and no irradiation of the internal mammary and medial supraclavicular (IM-MS) lymph nodes, all participating institutes were invited to

  13. Efecto de la adición de carragenina kappa i.ii y goma tara sobre características de calidad del jamón de cerdo picado y cocido.

    OpenAIRE

    Restrepo Molina, Diego Alonso; Molina Cote, Fabio Alexander; Cabrera Torres, Kenneth Roy

    2011-01-01

    Se evaluaron sinéresis, color y dureza instrumental y, sensorialmente las características de olor, sabor, color y dureza en jamones inyectados, cocidos y picados de cerdo, los cuales se habían elaborado aplicando en la salmuera de inyección una mezcla de hidrocoloides compuesta por carragenina kappa I.II y goma tara en una proporción de 79:21, en niveles del 1% y 1,2%, usando tres repeticiones para el estudio. Los jamones así elaborados se compararon contra un jamón testigo, elaborado sin el ...

  14. DECOVALEX - Mathematical models of coupled T-H-M processes for nuclear waste repositories. Executive summary for Phases I,II and III

    International Nuclear Information System (INIS)

    Jing, L.; Stephansson, O.; Tsang, C.F.; Kautsky, F.

    1996-06-01

    This executive summary presents the motivation, structure, objectives, methodologies and results of the first stage of the international DECOVALEX project - DECOVALEX I (1992-1995). The acronym stands for Development of Coupled Models and their Validation against Experiment in Nuclear Waste Isolation, and the project is an international effort to develop mathematical models, numerical methods and computer codes for coupled thermo-hydro-mechanical processes in fractured rocks and buffer materials for geological isolation of spent nuclear fuel and other radioactive wastes, and validate them against laboratory and field experiments. 24 refs

  15. Interpretation of electrocardiographic, echocardiographic and biochemical findings during different stages of Canine Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Ural K

    2017-09-01

    Full Text Available Objective. The purpose of the present study was to test the hypothesis that cardiac alterations participate within different stages of CVL. Materials and methods. Twenty-eight dogs were diagnosed with CVL, were classified [based on clinical signs, rapid ELISA/IFAT, hematological and serum biochemical tests, urinary protein/creatinine ratio, ECG and ECHO]. as follows; group I (mild disease, group II (moderate disease, group III (severe disease, group IV (very severe disease and group V included healthy controls. Results. Ig G antibodies against leishmaniasis as tested by IFAT, were deemed 1/64 to 1/16000 among infected groups. There were statistical significance regarding mean values for WBC [among healthy control group (V. and other groups (p=0.049], RBC [among stage III-stage IV and other groups (p=0.001], Hb [between stage I and stage III-stage IV (p=0.008, HCT [between stage I and other groups (p = 0.001] MCHC [between stage I and stage II- stage IV (p=0.046], serum creatinine [(p=0.008 stage IV and stage I-II within group V], serum protein [(p=0.002 among stage IV and stage I-III- healthy control groups] and serum albumine [(p=0.004 among stage IV and stage I-II]. There was no alteration in CTnI concentrations,among groups. UPC analysis revealed statistical difference among control group and stage II to IV dogs (p=0.000. Moderate or severe ECG abnormalities were detected in 6/28 of diseased dogs. Regarding ECHO examination LA/ Ao value presented significant difference (p=0.003 among stage IV and other groups. Conclusions. It may be suggested that establishing Leishvet Working Group to those of dogs classified into stage I to IV, ECG [left atrial/ventricular enlargement, myocardial hypoxia] and ECHO [left atrial dilation, decrased/increased LVIDs, decrased/increased LVIDd, shortened FS and EF (systolic dysfunction] alterations must be taken into account along with hematological and serum biochemical analysis.

  16. Experiences of social harm and changes in sexual practices among volunteers who had completed a phase I/II HIV vaccine trial employing HIV-1 DNA priming and HIV-1 MVA boosting in Dar es Salaam, Tanzania.

    Science.gov (United States)

    Tarimo, Edith A M; Munseri, Patricia; Aboud, Said; Bakari, Muhammad; Mhalu, Fred; Sandstrom, Eric

    2014-01-01

    Volunteers in phase I/II HIV vaccine trials are assumed to be at low risk of acquiring HIV infection and are expected to have normal lives in the community. However, during participation in the trials, volunteers may encounter social harm and changes in their sexual behaviours. The current study aimed to study persistence of social harm and changes in sexual practices over time among phase I/II HIV vaccine immunogenicity (HIVIS03) trial volunteers in Dar es Salaam, Tanzania. A descriptive prospective cohort study was conducted among 33 out of 60 volunteers of HIVIS03 trial in Dar es Salaam, Tanzania, who had received three HIV-1 DNA injections boosted with two HIV-1 MVA doses. A structured interview was administered to collect data. Analysis was carried out using SPSS and McNemars' chi-square (χ2) was used to test the association within-subjects. Participants reported experiencing negative comments from their colleagues about the trial; but such comments were less severe during the second follow up visits (χ2 = 8.72; Pstigma (χ2 = 6.06; Ptowards the HIV vaccine trial (χ2 = 4.9; Pcounselling and support appears important to minimize risky sexual behaviour among volunteers after participation in HIV Vaccine trials.

  17. TOP1 gene copy number and TOP1/CEN-20 ratio in stage III colorectal cancer samples

    DEFF Research Database (Denmark)

    Rømer, Maria Unni Koefoed; Nygård, Sune Boris; Christensen, Ib Jarle

    AIM OF STUDY To investigate if TOP1 gene copy number and/or the TOP1/CEN-20 ratio in colorectal cancer (CRC) areassociated with prognosis. BACKGROUND TOP1, localized on chromosome 20, encodes topoisomerase I (TOP1), which is the sole molecular target of irinotecan. TOP1 immunoreactivity in formalin...... gene copy number/cell and OS exists. A continuous relationship between TOP1 gene copy number/cell and LR exists. A continuous relationship exists between TOP1/CEN-20 ratio and LR CONCLUSION Our data suggest that TOP1 and TOP1/CEN-20 ratio are associated with prognosis in colorectal cancer. Future...... analyses on 50 FFPE primary CRC tissues. When compared with results from normal colorectal mucosa, 80 % of the tumors showed increased TOP1 gene copy number and 2/3 had increased TOP1/CEN-20 ratio. MATERIALS AND METHODS FFPE samples from 154 stage III CRC patients not receiving adjuvant chemotherapy were...

  18. Staging atmospheres

    DEFF Research Database (Denmark)

    Bille, Mikkel; Bjerregaard, Peter; Sørensen, Tim Flohr

    2015-01-01

    The article introduces the special issue on staging atmospheres by surveying the philosophical, political and anthropological literature on atmosphere, and explores the relationship between atmosphere, material culture, subjectivity and affect. Atmosphere seems to occupy one of the classic...

  19. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    Science.gov (United States)

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

  20. Determination of Fe2+ and Fe3+ species by FIA-CRC-ICP-MS in Antarctic ice samples

    DEFF Research Database (Denmark)

    Spolaor, A; Vallelonga, Paul Travis; Gabrieli, J

    2012-01-01

    contexts depends strongly on its oxidation state. Solubility in water and the capacity to form complexes are just two important characteristics that are species dependent. Distinguishing between the two iron species, Fe(II) and Fe(III), is necessary to evaluate bioavailability, as Fe(II) is more soluble......Iron is an element of great interest due to its role in primary production and in oceanic carbon cycle regulation, such that past changes in iron deposition may have influenced oceanic sequestration of atmospheric CO2 on millennial time scales. The behavior of iron in biological and environmental...... and therefore more readily available for phytoplankton uptake and growth. Here, we present a novel analytical method for iron speciation analysis using Collision Reaction Cell-Inductively Coupled Plasma-Mass Spectrometry (CRC-ICP-MS) and apply it to ice core samples from Talos Dome, Antarctica. The method...

  1. Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical stage.

    Science.gov (United States)

    Canossi, Angelica; Aureli, Anna; Del Beato, Tiziana; Rossi, Piero; Franceschilli, Luana; De Sanctis, Flavio; Sileri, Pierpaolo; di Lorenzo, Nicola; Buonomo, Oreste; Lauro, Davide; Venditti, Adriano; Sconocchia, Giuseppe

    2016-08-12

    NK cell cytotoxicity is regulated by the types of the interaction between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands on target cells and the different binding affinity of the Fcγ receptor IIIA (CD16A) for IgG-coated tumor cells. Thus, it is conceivable that KIR and CD16A gene contents may contribute to the function of NK cells by modulating an immune response in the colorectal carcinoma (CRC) microenvironment. This hypothesis is supported by recent evidence suggesting that NK cells improve the clinical course of CRC patients by enhancing the anti-CRC effect of CD8 + T cells. This information provides the rationale to test the hypothesis whether the independent KIR segregation and specificity, as well as CD16A gene polymorphisms, have an impact on CRC. Using polymerase chain reaction-sequence-specific primers (PCR-SSP) and sequence-based typing (SBT), we investigated KIR/HLA-C complex and CD16A (48H/R/L,158V/F) gene polymorphisms in 52 CRC patients and 61 local healthy controls (LCTRs). The allele frequency (AF) of at least five activating KIR (aKIRs) of the B haplotype (p = 0.036, OR 0.204), KIR2DL2 (p = 0.047, OR 0.2616), and KIR2DS2 genes (5.8 vs LCTR 13.8 % and vs. Fasano's CTR 16.3 %, p = 0.05, OR 0.3145), in the absence of their cognate HLA-C1 ligands, were significantly associated with a reduced genetic risk of CRC. In contrast, CD16A-48H polymorphism was positively associated with an increased genetic risk of CRC (p = 0.05, OR 2.761). The latter was also found to be correlated with advanced stages of disease [III and IV (p = 0.03, OR 3.625)]. Our data suggest that the analysis of aKIRs and KIR2DL2 gene and CD16A-48H may be of interest for the identification of individuals at reduced and increased genetic risk of CRC, respectively.

  2. Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer

    DEFF Research Database (Denmark)

    Andersen, C L; Christensen, L L; Thorsen, K

    2009-01-01

    The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and to evaluate their relation with the recurrence of stage II CRC and overall survival. Microarray-based transcript profiles of 20 normal mucosas and 424 CRC samples were used to identify 51...... cancers we found that high SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2-6.0; P=0.01). Analyses of approximately 1000 stage I-III adenocarcinomas, by immunohistochemistry, revealed that patients with tumours displaying high levels of CBFB and SMARCC1 proteins had a significantly...

  3. Experiences of social harm and changes in sexual practices among volunteers who had completed a phase I/II HIV vaccine trial employing HIV-1 DNA priming and HIV-1 MVA boosting in Dar es Salaam, Tanzania.

    Directory of Open Access Journals (Sweden)

    Edith A M Tarimo

    Full Text Available BACKGROUND: Volunteers in phase I/II HIV vaccine trials are assumed to be at low risk of acquiring HIV infection and are expected to have normal lives in the community. However, during participation in the trials, volunteers may encounter social harm and changes in their sexual behaviours. The current study aimed to study persistence of social harm and changes in sexual practices over time among phase I/II HIV vaccine immunogenicity (HIVIS03 trial volunteers in Dar es Salaam, Tanzania. METHODS AND RESULTS: A descriptive prospective cohort study was conducted among 33 out of 60 volunteers of HIVIS03 trial in Dar es Salaam, Tanzania, who had received three HIV-1 DNA injections boosted with two HIV-1 MVA doses. A structured interview was administered to collect data. Analysis was carried out using SPSS and McNemars' chi-square (χ2 was used to test the association within-subjects. Participants reported experiencing negative comments from their colleagues about the trial; but such comments were less severe during the second follow up visits (χ2 = 8.72; P<0.001. Most of the comments were associated with discrimination (χ2 = 26.72; P<0.001, stigma (χ2 = 6.06; P<0.05, and mistrust towards the HIV vaccine trial (χ2 = 4.9; P<0.05. Having a regular sexual partner other than spouse or cohabitant declined over the two follow-up periods (χ2 = 4.45; P<0.05. CONCLUSION: Participants in the phase I/II HIV vaccine trial were likely to face negative comments from relatives and colleagues after the end of the trial, but those comments decreased over time. In this study, the inherent sexual practice of having extra sexual partners other than spouse declined over time. Therefore, prolonged counselling and support appears important to minimize risky sexual behaviour among volunteers after participation in HIV Vaccine trials.

  4. A prospective phase I/II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix - acute toxicity and biomarker response analysis

    International Nuclear Information System (INIS)

    Chan, P.; Doll, C.; Oza, A.; Pintilie, M.; Levin, W.; Manchul, L.; Fyles, A.; Milosevic, M.

    2003-01-01

    To evaluate the toxicity and biomarker response of celecoxib (C) as a biologic modifier in combination with definitive chemoradiotherapy (CRT) in women with cervix cancer. Fifteen cervix patients were entered into the first phase of this prospective study between March 2001 and January 2002. FIGO stages included IB(2), IIB(8), IIIB(4), and IVA(1), and median age was 51 years (range 26-62). Celecoxib 400mg orally was given b.i.d. 2 weeks prior to, and during the CRT. Toxicity assessments were performed weekly up to 12 weeks following treatment prior to further accrual using the NCIC-CTC. Hypoxia (HP5) and interstitial fluid pressure (IFP) assays were performed at day 0 and 14. Eleven patients completed the prescribed therapy. Only 2 of 4 patients discontinued C due to GI toxicity. In total there were 6 (40%) with grade 3/4 acute toxicity. Four were related to GI, one to skin reaction while the other was haematological. Although it was difficult to distinguish CRT toxicity from C, the proportion of patients with severe acute toxicity was similar to what we previously reported with CRT alone (8/24 (33%), Rodrigues, IJROBP 2001:Vol 51:(3): (Supp 1): 334). GI toxicity was more common in this study whereas haematologic effects were more frequent in the previous study. Evaluating the most recent measurable data set, 6 of 16 patients showed a decrease in HP5, (3.8 - 89.7%) while 10 of 14 patients had a reduction in IFP, (1.3 - 16.2mmHg). Two grade 4 late GI toxicity developed. Celecoxib is tolerated by patients receiving CRT for cervix cancer. Response of microenvironmental biomarkers to C was seen in the majority, suggesting a role as early markers of treatment outcome. Further follow-up is needed to assess the risk of late toxicity. The trial has been re-opened with C reduced to 300 mg b.i.d

  5. A phase I-II study of the histone deacetylase inhibitor vorinostat plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced breast cancer.

    Science.gov (United States)

    Tu, Yifan; Hershman, Dawn L; Bhalla, Kapil; Fiskus, Warren; Pellegrino, Christine M; Andreopoulou, Eleni; Makower, Della; Kalinsky, Kevin; Fehn, Karen; Fineberg, Susan; Negassa, Abdissa; Montgomery, Leslie L; Wiechmann, Lisa S; Alpaugh, R Katherine; Huang, Min; Sparano, Joseph A

    2014-07-01

    Histone deacetylases (HDACs) are a family of enzymes that regulate chromatin remodeling and gene transcription. Vorinostat is a panHDAC inhibitor that sensitizes breast cancer cells to taxanes and trastuzumab by suppressing HDAC6 and Hsp90 client proteins. Fifty-five patients with clinical stage IIA-IIIC breast cancer received 12 weekly doses of paclitaxel (80 mg/m(2)) plus vorinostat (200-300 mg PO BID) on days 1-3 of each paclitaxel dose plus trastuzumab (for Her2/neu positive disease only), followed by doxorubicin/cyclophosphamide (60/600 mg/m(2) every 2 weeks plus pegfilgrastim). The primary study endpoint was pathologic complete response (pCR). pCR occurred in 13 of 24 evaluable patients with Her2-positive disease (54, 95 % confidence intervals [CI] 35-72 %), which met the prespecified study endpoint. pCR occurred in 4 of 15 patients with triple negative disease (27, 95 % CI 11-52 %) and none of 12 patients with ER-positive, Her2/neu negative disease (0, 95 % CI 0-24 %), which did not meet the prespecified endpoint. ER-positive tumors exhibited lower Ki67 and higher Hsp70 expression, and HDAC6, Hsp70, p21, and p27 expression were not predictive of response. Vorinostat increased acetylation of Hsp90 and alpha tubulin, and reduced expression of Hsp90 client proteins and HDAC6 in the primary tumor. Combination of vorinostat with weekly paclitaxel plus trastuzumab followed by doxorubicin-cyclophosphamide is associated with a high pCR rate in locally advanced Her2/neu positive breast cancer. Consistent with cell line and xenograft data, vorinostat increased acetylation of Hsp90 and alpha tubulin, and decreased Hsp90 client protein and HDAC6 expression in human breast cancers in vivo.

  6. Identification of the TP53-induced glycolysis and apoptosis regulator in various stages of colorectal cancer patients

    Science.gov (United States)

    AL-KHAYAL, KHAYAL; ABDULLA, MAHA; AL-OBEED, OMAR; KATTAN, WAEL AL; ZUBAIDI, AHMAD; VAALI-MOHAMMED, MANSOOR-ALI; ALSHEIKH, ABDULMALIK; AHMAD, REHAN

    2016-01-01

    The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene known to regulate glycolysis by acting as fructose bis-phosphatase (FBPase) and modulate reactive oxygen species. TIGAR expression has been implicated in oncogenesis and progression of several human cancers. However, TIGAR expression is not known in various stages of colorectal cancer (CRC). There is an increase in the colorectal cancer incidence in Saudi Arabia. We sought to analyze TIGAR expression in this ethnic group. The aim of this study was to investigate the TIGAR expression in colorectal cancer (CRC) patients from Saudi Arabia. Tissue microarray (TMA) was constructed from 22 matched colorectal tumor tissues and adjacent normal tissues. TIGAR expression was examined in TMA slide using immunohistochemistry. TIGAR mRNA was determined in 14 matched tumor tissue and adjacent normal tissue. TIGAR protein expression was also examined in CRC tumor tissues and cell lines. Statistical analyses (t-test) were applied to evaluate the significance of TIGAR expression. TIGAR mRNA level was upregulated significantly in stage II (pcolorectal cancer. Strong TIGAR positive staining was found in 68% (15/22) of the tumor samples with nuclear localization. TIGAR staining was found to be significantly increased in early stage (stage I and II) CRC (pcolorectal cancer tissues and CRC cell lines. These findings indicate that TIGAR is highly expressed at the mRNA and protein levels in colorectal cancer with prominent nuclear localization. TIGAR expression may be used as a bio-marker for detection of colorectal cancer and can be used as a target for developing therapeutics for the treatment of colorectal cancer. PMID:26675982

  7. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

    Directory of Open Access Journals (Sweden)

    Spugnini Enrico P

    2011-12-01

    the quality of life in pets with down staged cancer and in the majority of the treated animals PPI were well tolerated. Further studies are warranted to assess the efficacy of this strategy in patients with advanced cancers in companion animals as well as in humans.

  8. Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression.

    Science.gov (United States)

    Reguart, Noemi; Rosell, Rafael; Cardenal, Felipe; Cardona, Andres F; Isla, Dolores; Palmero, Ramon; Moran, Teresa; Rolfo, Christian; Pallarès, M Cinta; Insa, Amelia; Carcereny, Enric; Majem, Margarita; De Castro, Javier; Queralt, Cristina; Molina, Miguel A; Taron, Miquel

    2014-05-01

    Vorinostat or suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with demonstrated antiproliferative effects due to drug-induced accumulation of acetylated proteins, including the heat shock protein 90. We prospectively studied the activity of vorinostat plus erlotinib in EGFR-mutated NSCLC patients with progression to tyrosine kinase inhibitors. We conducted this prospective, non-randomized, multicenter, phase I/II trial to evaluate the maximum tolerated dose, toxicity profile and efficacy of erlotinib and vorinostat. Patients with advanced NSCLC harboring EGFR mutations and progressive disease after a minimum of 12 weeks on erlotinib were included. The maximum tolerated dose of vorinostat plus erlotinib was used as recommended dose for the phase II (RDP2) to assess the efficacy of the combination. The primary end point was progression-free-survival rate at 12 weeks (PFSR12w). Pre-treatment plasma samples were required to assess T790M resistant mutation. A total of 33 patients were enrolled in the phase I-II trial. The maximum tolerated dose was erlotinib 150 mg p.o., QD, and 400mg p.o., QD, on days 1-7 and 15-21 in a 28-day cycle. Among the 25 patients treated at the RDP2, the most common toxicities included anemia, fatigue and diarrhea. No responses were observed. PFSR12w was 28% (IC 95%: 18.0-37.2); median progression-free survival (PFS) was 8 weeks (IC 95%: 7.43-8.45) and overall survival (OS) 10.3 months (95% CI: 2.4-18.1). Full dose of continuous erlotinib with vorinostat 400mg p.o., QD on alternative weeks can be safely administered. Still, the combination has no meaningful activity in EGFR-mutated NSCLC patients after TKI progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. A multi-institutional study of outcomes in stage I–III uterine carcinosarcoma

    Science.gov (United States)

    Dickson, Elizabeth L.; Vogel, Rachel Isaksson; Gehrig, Paola A.; Pierce, Stuart; Havrilesky, Laura; Secord, Angeles Alvarez; Dottino, Joseph; Fader, Amanda N.; Ricci, Stephanie; Geller, Melissa A.

    2016-01-01

    Objective To evaluate the use of adjuvant therapy after primary surgery for stage I–III uterine carcinosarcoma (CS). Methods A multi-institutional retrospective study of women with stage I–III CS was conducted. Analyses were stratified by stage (I/II and III). Patients were categorized according to adjuvant therapy: observation (OBS), radiation (RT), chemotherapy (CT) or multimodal therapy (CT + RT). Overall survival (OS) and progression-free survival (PFS) were analyzed using log-rank tests and Cox proportional hazards models. Results 303 patients were identified across four institutions: 195 with stage I/II and 108 with stage III disease. In stage I/II disease, 75 (39.9%) received OBS, 33 (17.6%) CT, 37 (19.7%) RT, and 43 (22.9%) CT + RT. OBS was associated with a fourfold increased risk of death compared to CT (adjusted hazard ratio (aHR) = 4.48, p = 0.003). Patients receiving CT + RT had significantly improved PFS compared to those receiving CT alone (aHR = 0.43, p = 0.04), but no difference in OS. In the stage III cohort, 16 (15.0%) received OBS, 34 (31.8%) CT, 20 (18.7%) RT, and 37 (34.6%) CT + RT. OBS was associated with worse OS and PFS compared to CT (OS: aHR = 2.46, p = 0.04; PFS: aHR = 2.39, p = 0.03, respectively). A potential improvement in PFS was seen for those treated with CT + RT compared to CT alone, however it was not statistically significant (aHR = 0.53, p = 0.09). Conclusions Observation after surgery was associated with poor outcomes in uterine CS compared to CT and RT alone. Multimodality therapy for women with stage I/II disease was associated with improved PFS compared to chemotherapy alone. Novel treatment options are needed to improve outcomes in this aggressive disease. PMID:26348313

  10. Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I-II trial

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnt, T.; Pigorsch, S.; Pelz, T.; Haensgen, G.; Dunst, J. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Becker, A. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Dept. of Radiotherapy, Municipial Hospital, Dessau (Germany); Bloching, M.; Passmann, M. [Dept. of Head and Neck Surgery, Martin Luther Univ., Halle (Germany); Lotterer, E. [Dept. of Internal Medicine I, Martin Luther Univ., Halle (Germany)

    2003-10-01

    We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m{sup 2} on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m{sup 2} twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 {+-} 61 cm{sup 3}. The mean follow-up was 30 months (range 4-39 months). Results: One early death (peritonitis and sepsis a t day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m{sup 2} paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m{sup 2} twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30

  11. Precision and accuracy control of dose calibrator: CAPINTEC CRC 12 in laboratory for radiopharmacy of Nuclear Medicine Institute of Sucre, Bolivia; Control de precision y exactitud del calibrador de dosis: CAPINTEC CRC 12 del Laboratorio de Radiofarmacia del Instituto de Medicina Nuclear Sucre

    Energy Technology Data Exchange (ETDEWEB)

    Huanca Sardinas, E; Castro Sacci, O; Torrez Cabero, M; Vasquez Ibanez, M.R; Zambrana Zelada, AJ., E-mail: nuclear_sre@entelnet.bo, E-mail: ehuancasardinas@hotmail.com, E-mail: marcetorrez@hotmail.com, E-mail: maritavas@yahoo.es, E-mail: alfzambrana@gmail.com [Universidad Mayor Real y Pontifica de San Francisco Xavier de Chuquisaca, Sucre (Bolivia, Plurinational State of). Radiofarmacia - Instituto de Medicina Nuclear de Sucre. Hospital Santa Barbara

    2013-11-01

    The dose calibrator is one of the indispensable tools in radiopharmacy laboratories of a nuclear medicine department also is mandated to provide accurate readings. A very high doses produce unnecessary radiation exposure to the patient or a very low dose, prolong the acquisition time of the studies affecting the quality of the image. In the present work we did a retrospective analysis of the results of quality checks performed at precision accuracy of the Gauge CRC12 CAPINTEC dose calibrator over a period of 16 years, using sealed certified sources with low power, medium and high: Ba{sup 133} , Cs{sup 137} , Co{sup 60} and Co{sup 57}. The results showed that the lowest standard deviation value was 0.17 for Ba133, relative to Co{sup 57} of 2.97 in the control of accuracy. Accuracy over control values were also lower standard deviation for Ba{sup 133} 1.00, relative to Co{sup 57} 10.06. Being stated that the CRC12 CAPINTEC activimeter reliability is acceptable during the reporting period and under the conditions indicated. Therefore, we continue to make these quality control procedures and the professional must feel confident that the measurements obtained with it are reliable.

  12. Staging Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    In recent years, the social sciences have taken a “mobilities turn.” There has been a developing realisation that mobilities do not “just happen.” Mobilities are carefully and meticulously designed, planned and staged (from above). However, they are equally importantly acted out, performed and li......, the book asks: what are the physical, social, technical, and cultural conditions to the staging of contemporary urban mobilities?...... that mobility is more than movement between point A and B. It explores how the movement of people, goods, information, and signs influences human understandings of self, other and the built environment. Moving towards a new understanding of the relationship between movement, interaction and environments...

  13. The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Min, Byung-Hoon; Kim, Kyoung-Mee; Kang, Gyeong Hoon; Bae, Jeong Mo; Lee, Eui Jin; Yu, Hong Suk; Kim, Young-Ho; Chang, Dong Kyung; Kim, Hee Cheol; Park, Cheol Keun; Lee, Suk-Hee

    2011-01-01

    Colorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear. A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status. CIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022). Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results

  14. Mechanisms of topoisomerase I (TOP1) gene copy number increase in a stage III colorectal cancer patient cohort

    DEFF Research Database (Denmark)

    Smith, David Hersi; Christensen, Ib Jarle; Jensen, Niels Frank

    2013-01-01

    Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III C...

  15. Predictive value of pretreatment lymphocyte count in stage II colorectal cancer and in high-risk patients treated with adjuvant chemotherapy.

    Science.gov (United States)

    Liang, Lei; Zhu, Ji; Jia, Huixun; Huang, Liyong; Li, Dawei; Li, Qingguo; Li, Xinxiang

    2016-01-05

    Pretreatment lymphocyte count (LC) has been associated with prognosis and chemotherapy response in several cancers. The predictive value of LC for stage II colorectal cancer (CRC) and for high-risk patients treated with adjuvant chemotherapy (AC) has not been determined. A retrospective review of prospectively collected data from 1332 consecutive stage II CRC patients who underwent curative tumor resection was conducted. A pretreatment LC value risk, 459 (62.2%) of whom received AC. Patients with low LCs had significantly worse 5-year OS (74.6% vs. 90.2%, p risk patients with low LCs had the poorest DFS (p value or combined with high-risk status were both independent prognostic factors(p risk, AC-treated patients with high LCs had significantly longer DFS than untreated patients (HR, 0.594; 95% CI, 0.364-0.970; p = 0.035). There was no difference or trend for DFS or OS in patients with low LCs, regardless of the use of AC (DFS, p = 0.692; OS, p = 0.522). Low LC was also independently associated with poorer DFS in high-risk, AC-treated patients (HR, 1.885; 95% CI, 1.112-3.196; p = 0.019). Pretreatment LC is an independent prognostic factor for survival in stage II CRC. Furthermore, pretreatment LC reliably predicts chemotherapeutic efficacy in high-risk patients with stage II CRC.

  16. Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG Study

    Directory of Open Access Journals (Sweden)

    Arie Figer, Aviram Nissan, Adi Shani, Riva Borovick, Mariana Stiener, Mario Baras, Herbert R. Freund, Aaron Sulkes, Alexander Stojadinovic, Tamar Peretz

    2011-01-01

    Full Text Available Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC. This study evaluates long-term (10-year outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV or 5-FU/Levamisole (5FU+LEV.Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months.Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02 and gastrointestinal toxicity with 5FU+LV (p=0.03. Female patients treated with 5FU+LEV had improved overall survival.Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

  17. Clinical impact of FDG-PET/CT on colorectal cancer staging and treatment strategy

    DEFF Research Database (Denmark)

    Petersen, Rasmus K; Hess, Søren; Alavi, Abass

    2014-01-01

    and patients divided as follows: (A) Patients with a change in therapy following FDG-PET/CT and (B) Patients without a change following FDG-PET/CT. Sixty-two patients had colon and five had rectal cancer. Of these, 20 (30%; CI 20.2-41.7) belonged to group A, whereas 47 (70%; CI 58.3-79.8) fell in group B......FDG-PET/CT is rarely used for initial staging of patients with colorectal cancer (CRC). Surgical resection of primary tumor and isolated metastases may result in long-term survival or presumed cure, whereas disseminated disease contraindicates operation. We analyzed a retrospective material...... to elucidate the potential value of FDG-PET/CT for staging of CRC. Data were retrieved from 67 consecutive patients (24-84 years) with histopathologically proven CRC who had undergone FDG-PET/CT in addition to conventional imaging for initial staging. Treatment plans before and after FDG-PET/CT were compared...

  18. Radiation therapy planning for early-stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Maraldo, Maja V; Dabaja, Bouthaina S; Filippi, Andrea R

    2015-01-01

    PURPOSE: Early-stage Hodgkin lymphoma (HL) is a rare disease, and the location of lymphoma varies considerably between patients. Here, we evaluate the variability of radiation therapy (RT) plans among 5 International Lymphoma Radiation Oncology Group (ILROG) centers with regard to beam arrangements......, planning parameters, and estimated doses to the critical organs at risk (OARs). METHODS: Ten patients with stage I-II classic HL with masses of different sizes and locations were selected. On the basis of the clinical information, 5 ILROG centers were asked to create RT plans to a prescribed dose of 30...... axillary disease, and 1 had disease in the neck only. The median age at diagnosis was 34 years (range, 21-74 years), and 5 patients were male. Of the resulting 50 treatment plans, 15 were planned with volumetric modulated arc therapy (1-4 arcs), 16 with intensity modulated RT (3-9 fields), and 19 with 3...

  19. Changing Therapeutic Paradigms: Predicting mCRC Lesion Response to Selective Internal Radionuclide Therapy (SIRT based on Critical Absorbed Dose Thresholds: A Case Study

    Directory of Open Access Journals (Sweden)

    Kathy W

    2017-01-01

    Full Text Available A 65 year old male with metastatic colorectal cancer (mCRC in the liver was referred for selective internal radionuclide therapy (SIRT following a history of extensive systemic chemotherapy. 90Y PET imaging was performed immediately after treatment and used to confirm lesion targeting and measure individual lesion absorbed doses. Lesion dosimetry was highly predictive of eventual response in the follow-up FDG PET performed 8 weeks after therapy. The derived radiation dose map was used to plan a second SIRT procedure aiming to protect healthy liver by keeping absorbed dose below the critical dose threshold, whilst targeting the remaining lesions that had received sub-critical dosing. Again, 90Y PET was performed immediately post-treatment and used to derive absorbed dose measures to both lesions and healthy parenchyma. Additional followup FDG PET imaging again confirmed the role of the 90Y PET dose map as an early predictor of response, and a tool for safe repeat treatment planning.

  20. Destan Geleneğinden Tarihi Romana: Tölögön Kasımbek ve Kırılan Kılıç I,II From Legend Tradition to Historical Novels: Tölögön Kasımbek and Broken Sword I,II

    Directory of Open Access Journals (Sweden)

    Canan OLPAK KOÇ

    2012-09-01

    Full Text Available Being a social entity, humanity has been searching the ways of transferring their feelings, thoughts, imaginations and impressions to next generations all the time. Before written expressions became widespread, they used to try to accomplish this aim with the help of verbal folk literature. In this sense, epic had become the most significant tool to transfer experiences not only for individuals but also for communities. After written expressions became widespread, epic gave its place to written literature genres like novel and story. However, those narrative genres have been written by individual authors and they have reflected cultures which they had grown in to their works. Kyrgyz have a considerably old past. Interaction between Turkish Literature and Kyrgyz Literature had developed pretty limited because of several reasons. Especially in period when there was no relation with Kyrgyzstan, there had been very few publications about the Kyrgyz Literature. With increasing relations after the year of 1990, Kyrgyz Literature began known. Bringing Kırılan Kılıç I (Broken Sword I and Kırılan Kılıç II (Broken Sword II novels, which are belong to Tölögön Kasımbek, in to Turkish Literature is the product of increasing interest in this period. It is important that how the man understand the story of existance and how he/she tell the existence of the public. Tölögön Kasımbek, in his novels Kırılan Kılıç I ,II (Broken Sword I,II has told the adventure of kyrgyz people and how they’d been destroyed by being defeated by the Russians. The book can be accepted as a legendary historical novel within this aspects. We, in this study, will see how close are the epic motifs of the Tölögön who wrote the history of Kyrgyz, to the reali ty which the historical novels never leaves. Toplumsal bir varlık olarak insan duygularını, düşüncelerini, hayallerini, izlenimlerini her zaman bir sonraki nesle aktarmanın yolunu aramıştır. Yazılı kültür yaygınlaşmadan önce bunu sözlü halk edebiyatı türleri ile yapmaya çalışmıştır. Bu anlamda destanlar sadece bireyin değil milletlerin deneyimlerini aktarmada en önemli araç olmuştur. Yazılı kültürün yaygınlaşması ile birlikte destanların yerini roman, hikâye gibi edebi türler almıştır. Ancak bu anlatı türleri tek bir kişi tarafından yazılmıştır. Fakat yazar içinde yetiştiği toplumun kültürünü yazdığı esere aktarmaktadır. Kırgızların oldukça eskiye dayanan bir geçmişleri vardır. Türk yazınının Kırgız Edebiyatıyla ilişkisi, çeşitli etmenlere dayalı olarak oldukça sınırlı gelişmiştir. Özellikle Kırgızistan ile ilişkilerin olmadığı dönemde Kırgız edebiyatıyla ilgili neşriyat da çok az olmuştur. 1990 yılı sonrasında artan ilişkilerle beraber Kırgız edebiyatı tanınmaya başlar. Tölögön Kasımbek’e ait Kırılan Kılıç I- Kırılan Kılıç II romanlarının Türkiye Türkçesine kazandırılması da bu dönemde artan ilginin bir ürünüdür. İnsanın var oluş öyküsünü nasıl anladığı ve toplumun varlığını nasıl anlattığı önemlidir. Bu çerçeve de Tölögön Kasımbek, destansı özellikler çerçevesinde ve tarihi roman bağlamında değerlendirilecek olan Kırılan Kılıç I ve II romanında Kırgız halkının var oluş serüvenini ve Ruslar karşısında nasıl yenilgiye uğrayıp yıkıldığını anlatmıştır. Tarihi roman henüz kesin olarak tanımı yapılamasa da tarihsel bir bilginin edebi duyarlılıklar eşliğinde romana dönüştürülmesidir diyebiliriz. Biz bu çalışmamızda Kırgızlarının tarihini yazıya döken Tölögön’ün destana ait motifleri tarihi romanın elden bırakmadığı gerçekliğe ne kadar yaklaştırdığını göreceğiz.

  1. Number of Lymph Node Metastases May Indicate the Regimen for Adjuvant Chemotherapy in Patients with Stage III Colorectal Cancer.

    Science.gov (United States)

    Ando, Koji; Oki, Eiji; Saeki, Hiroshi; Kasagi, Yuta; Tsuda, Yasuo; Zaitsu, Yoko; Nakashima, Yuichiro; Imamura, Y U; Ohgaki, Kippei; Maehara, Yoshihiko

    2015-11-01

    Adjuvant chemotherapy (ACT) may prevent recurrence in patients with stage III colorectal cancer (CRC). However, only 10% of patients benefit from ACT and no effective indicators exist to predict which patients are likely to benefit. The present study validated metastatic lymph node (MLN) number as a new indicator for ACT. We retrospectively reviewed 173 patients with stage III CRC, who were classified by Union for International Cancer Control (UICC) stage or N category, and analyzed their overall survival (OS) and disease-free survival (DFS) according to stage, number of MLNs and ACT use. Among 173 patients, we found 65 with only one MLN (N1a). For N1a patients treated with ACT, the 5-year OS rate was 100%; the 3-year DFS rate was 92.7% for those treated with oral ACT. The number of MLNs is a simple indicator for ACT in patients with stage III CRC. For patients with only one MLN, oral chemotherapy is a good option. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer.

    Science.gov (United States)

    Mohan, H M; Ryan, E; Balasubramanian, I; Kennelly, R; Geraghty, R; Sclafani, F; Fennelly, D; McDermott, R; Ryan, E J; O'Donoghue, D; Hyland, J M P; Martin, S T; O'Connell, P R; Gibbons, D; Winter, Des; Sheahan, K

    2016-11-01

    Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes. Copyright © 2016. Published by Elsevier Ltd.

  3. The prognostic value of lymph node yield in the earliest stage of colorectal cancer: a multicenter cohort study.

    Science.gov (United States)

    Backes, Yara; Elias, Sjoerd G; Bhoelan, Bibie S; Groen, John N; van Bergeijk, Jeroen; Seerden, Tom C J; Pullens, Hendrikus J M; Spanier, Bernhard W M; Geesing, Joost M J; Kessels, Koen; Kerkhof, Marjon; Siersema, Peter D; de Vos Tot Nederveen Cappel, Wouter H; van Lelyveld, Niels; Wolfhagen, Frank H J; Ter Borg, Frank; Offerhaus, G Johan A; Lacle, Miangela M; Moons, Leon M G

    2017-07-14

    In patients with stage II colorectal cancer (CRC) the number of surgically retrieved lymph nodes (LNs) is associated with prognosis, resulting in a minimum of 10-12 retrieved LNs being recommended for this stage. Current guidelines do not provide a recommendation regarding LN yield in T1 CRC. Studies evaluating LN yield in T1 CRC suggest that such high LN yields are not feasible in this early stage, and a lower LN yield might be appropriate. We aimed to validate the cut-off of 10 retrieved LNs on risk for recurrent cancer and detection of LN metastasis (LNM) in T1 CRC, and explored whether this number is feasible in clinical practice. Patients diagnosed with T1 CRC and treated with surgical resection between 2000 and 2014 in thirteen participating hospitals were selected from the Netherlands Cancer Registry. Medical records were reviewed to collect additional information. The association between LN yield and recurrence and LNM respectively were analyzed using 10 LNs as cut-off. Propensity score analysis using inverse probability weighting (IPW) was performed to adjust for clinical and histological confounding factors (i.e., age, sex, tumor location, size and morphology, presence of LNM, lymphovascular invasion, depth of submucosal invasion, and grade of differentiation). In total, 1017 patients with a median follow-up time of 49.0 months (IQR 19.6-81.5) were included. Four-hundred five patients (39.8%) had a LN yield ≥ 10. Forty-one patients (4.0%) developed recurrence. LN yield ≥ 10 was independently associated with a decreased risk for recurrence (IPW-adjusted HR 0.20; 95% CI 0.06-0.67; P = 0.009). LNM were detected in 84 patients (8.3%). LN yield ≥ 10 was independently associated with increased detection of LNM (IPW-adjusted OR 2.27; 95% CI 1.39-3.69; P = 0.001). In this retrospective observational study, retrieving < 10 LNs was associated with an increased risk of CRC recurrence, advocating the importance to perform an appropriate

  4. A Randomized Phase I/II Trial to Compare Weekly Usage with Triple Weekly Usage of Paclitaxel in Concurrent Radiochemotherapy for Patients with Locally Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Anhui SHI

    2011-03-01

    Full Text Available Background and objective Although the guidelines of the National Comprehensive Cancer Network of USA recommend that the standard therapy for locally advanced non-small cell lung cancer (LANSCLC is concurrent chemoradiotherapy. There is ongoing controversy about the treatment regimen which combines chemotherapy concurrently with radiotherapy. The aim of this study is to compare weekly usage with triple weekly usage of paclitaxel in concurrent radiochemotherapy for patients with LANSCLC, and to obtain the best paclitaxel regimen in the concurrent radiochemotherapy. Methods From April 2006 to April 2009, some LANSCLC patients in multicenter were randomly divided into weekly usage (45 mg/m2, 1 times/week, a total of 270 mg/m2 in six weeks and triple weekly usage (15 mg/m2, 3 times/week, a total of 270 mg/m2 in six weeks group of paclitaxel by a random number table. All patients were treated with 3D radiotherapy, and 95% planning target volume (PTV received a prescription dose of (60-70 Gy/(30-35times/(6-7weeks, (1.8-2.0 Gy/fraction. Then the side effects, response and overall survival rate were compared between two groups of patients. Results Thirty-eight LANSCLC patients were enrolled. Weekly usage and triple weekly usage group were 20 and 18 patients, respectively. In the triple weekly usage group, the side effects were 12 patients had radiation esophagitis of I-II degree, 1 patient had radiation esophagitis of III degree, 2 patients had radiation pneumonitis of I degree, 1 patient had radiation pneumonitis of II degree, 1 patient had radiation pneumonitis of III degree and died of respiratory failure, 2 patients developed weight loss of I degree. In the weekly usage group, the side effects were 11 patients had radiation esophagitis of I-III degree, 6 patients had radiation pneumonitis of II-III degree, 2 patients developed weight loss of I degree, 6 patients developed leucopenia of III-IV degree. The response rate of two groups was 88.8% and 50

  5. IIIST1\\NTI-i\\III.

    African Journals Online (AJOL)

    The similarity of these reports to the UFO reports of our own times is striking. But it is suggested that this piece of the jigsaw puzzle does fit. It certainly would explain why itwas necessary to develop the anti-aircraft guns and to demon- strate one of them in public in the presence of such distinguished guests in September ...

  6. Luuleekspordi transpordiprobleeme I-II / Ilmar Laaban

    Index Scriptorium Estoniae

    Laaban, Ilmar, 1921-2000

    1997-01-01

    Varem ilm. Välis-Eesti, 1983, 29. aug. ja 12. okt. Rets. rmt.: Våra sånger fick vi med oss : [Oma laulud tõime endaga kaasa : eesti luule antoloogia] / koost. ja tlk. Silvia Airik-Priuhka. Stockholm : Välis-Eesti ; EMP, 1983

  7. Thrillerens kunst: Forbrydelsen I-III

    DEFF Research Database (Denmark)

    Agger, Gunhild

    2012-01-01

    Dansk tv-drama har i 2011 og 2012 været genstand for en international reception af omfattende dimensioner. Denne interesse begyndte med Forbrydelsen. Den har især fokuseret på den danske produktionsmodel og det fænomen, der er blevet døbt ’Nordic Noir’. I denne artikel vil nogle af de spørgsmål...

  8. IIIST1\\NTI-i\\III.

    African Journals Online (AJOL)

    guests in September 1914. (1) Major-General Sir Lothian Nicholson. KCB, CMG, and Major H 1. MacMullen, MC, History of the East Lancashire Regiment in the Great. War 1914-1918, Littlebury. Bros, Ltd. Liverpool,. 1936. p 114. Ti\\.~TI(~S-1\\ IIIST ••III. ~SI Til VI~V. I..•f :01 i\\. f~•• 10III.SOIl ~IIII~ 1~lt. The study of military tactics ...

  9. Revised Editor's Note pp.i-iii

    African Journals Online (AJOL)

    Jimmy Gitonga

    Third, there is the need for African scholars to adopt innovative approaches to research in the social sciences. In this regard, James Njihia outlines critical realism, a relatively new philosophy of science, in an attempt to increase awareness of it amongst African researchers. Critical realism is a radical challenge to Western.

  10. Fibre intake and incident colorectal cancer depending on fibre source, sex, tumour location and Tumour, Node, Metastasis stage.

    Science.gov (United States)

    Vulcan, Alexandra; Brändstedt, Jenny; Manjer, Jonas; Jirström, Karin; Ohlsson, Bodil; Ericson, Ulrika

    2015-09-28

    Studies on fibre intake and incident colorectal cancer (CRC) indicate inverse associations. Differences by tumour stage have not been examined. We examined associations between fibre intake and its sources, and incidental CRC. Separate analyses were carried out on the basis of sex, tumour location and the Tumour, Node, Metastasis (TNM) classification. The Malmö Diet and Cancer Study is a population-based cohort study, including individuals aged 45-74 years. Dietary data were collected through a modified diet history method. The TNM classification was obtained from pathology/clinical records and re-evaluated. Among 27 931 individuals (60% women), we found 728 incident CRC cases during 428 924 person-years of follow-up. Fibre intake was inversely associated with CRC risk (P(trend) = 0.026). Concerning colon cancer, we observed borderline interaction between fibre intake and sex (P = 0.052) and significant protective association restricted to women (P(trend) = 0.013). Intake of fruits and berries was inversely associated with colon cancer in women (P(trend) = 0.022). We also observed significant interactions between intakes of fibre (P = 0.048) and vegetables (P = 0.039) and sex on rectal cancer, but no significant associations were seen between intake of fibre, or its sources, in either of the sexes. Except for inverse associations between intake of fibre-rich cereal products and N0- and M0-tumours, we did not observe significant associations with different TNM stages. Our findings suggest different associations between fibre intake and CRC depending on sex, tumour site and fibre source. High fibre intake, especially from fruits and berries, may, above all, prevent tumour development in the colon in women. No clear differences by TNM classification were detected.

  11. A randomized Phase I/II Trial of HQK-1001, an oral fetal globin gene inducer, in β–thalassaemia intermedia and HbE/β–thalassaemia

    Science.gov (United States)

    Fucharoen, Suthat; Inati, Adlette; Siritanaratku, Noppadol; Thein, Swee Lay; Wargin, William C.; Koussa, Suzanne; Taher, Ali; Chaneim, Nattawara; Boosalis, Michael; Berenson, Ronald; Perrine, Susan P.

    2014-01-01

    β–thalassemia intermedia syndromes (BTI) cause hemolytic anemia, ineffective erythropoiesis, and widespread complications. Higher fetal globin expression within genotypes reduces globin imbalance and ameliorates anemia. Sodium 2,2 dimethylbutyrate (HQK-1001), an orally bioavailable short-chain fatty acid derivative, induces γ-globin expression experimentally and is well-tolerated in normal subjects. Accordingly, a randomized, blinded, placebo-controlled, Phase I/II trial was performed in 21 adult BTI patients (14 with HbE/β0 thalassemia and 7 with β+/β0 thalassemia intermedia, to determine effective doses for fetal globin induction, safety, and tolerability. HQK-1001 or placebo were administered once daily for 8 weeks at four dose levels (10, 20, 30, or 40 mg/kg/day), and subjects were monitored for laboratory and clinical events. Pharmacokinetic profiles demonstrated a t1/2 of 10–12 hours. Adverse events with HQK-1001 treatment were not significantly different from placebo treatment. Median HbF increased with the 20 mg/kg treatment doses above baseline levels by 6.6% and 0.44 g/dL (p <0.01) in 8/9 subjects; total hemoglobin (Hgb) increased by a mean of 1.1 gm/dL in 4/9 subjects. These findings identify a safe oral therapeutic which induces fetal globin in BTI. Further investigation of HQK-1001 with longer dosing to definitively evaluate its hematologic potential appears warranted. PMID:23530969

  12. MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy

    International Nuclear Information System (INIS)

    Bos, Willemien van den; Bruin, D.M. de; Randen, A. van; Engelbrecht, M.R.W.; Postema, A.W.; Muller, B.G.; Zondervan, P.J.; Laguna Pes, M.P.; Reijke, T.M. de; Rosette, J.J.M.C.H. de la; Varkarakis, I.M.; Skolarikos, A.; Savci-Heijink, C.D.; Jurhill, R.R.; Wijkstra, H.

    2016-01-01

    Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H and E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. (orig.)

  13. A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma

    International Nuclear Information System (INIS)

    Roeder, Falk; Hensley, Frank W; Buechler, Markus W; Debus, Juergen; Koch, Moritz; Weitz, Juergen; Bischof, Marc; Schulz-Ertner, Daniela; Nikoghosyan, Anna V; Huber, Peter E; Edler, Lutz; Habl, Gregor; Krempien, Robert; Oertel, Susanne; Saleh-Ebrahimi, Ladan

    2012-01-01

    Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT) are considered. The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy) followed by surgery and IORT (10–12 Gy) in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. NCT01566123

  14. Clinical phase I/II trial to investigate neoadjuvant intensity-modulated short term radiation therapy (5 × 5 gy) and intraoperative radiation therapy (15 gy) in patients with primarily resectable pancreatic cancer - NEOPANC

    International Nuclear Information System (INIS)

    Roeder, Falk; Debus, Juergen; Huber, Peter E; Werner, Jens; Timke, Carmen; Saleh-Ebrahimi, Ladan; Schneider, Lutz; Hackert, Thilo; Hartwig, Werner; Kopp-Schneider, Annette; Hensley, Frank W; Buechler, Markus W

    2012-01-01

    The current standard treatment, at least in Europe, for patients with primarily resectable tumors, consists of surgery followed by adjuvant chemotherapy. But even in this prognostic favourable group, long term survival is disappointing because of high local and distant failure rates. Postoperative chemoradiation has shown improved local control and overalls survival compared to surgery alone but the value of additional radiation has been questioned in case of adjuvant chemotherapy. However, there remains a strong rationale for the addition of radiation therapy considering the high rates of microscopically incomplete resections after surgery. As postoperative administration of radiation therapy has some general disadvantages, neoadjuvant and intraoperative approaches theoretically offer benefits in terms of dose escalation, reduction of toxicity and patients comfort especially if hypofractionated regimens with highly conformal techniques like intensity-modulated radiation therapy are considered. The NEOPANC trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant short course intensity-modulated radiation therapy (5 × 5 Gy) in combination with surgery and intraoperative radiation therapy (15 Gy), followed by adjuvant chemotherapy according to the german treatment guidelines, in patients with primarily resectable pancreatic cancer. The aim of accrual is 46 patients. The primary objectives of the NEOPANC trial are to evaluate the general feasibility of this approach and the local recurrence rate after one year. Secondary endpoints are progression-free survival, overall survival, acute and late toxicity, postoperative morbidity and mortality and quality of life. http://www.clinicaltrials.gov/ct2/show/NCT01372735

  15. A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT and intraoperative radiation therapy (IORT in patients with retroperitoneal soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Roeder Falk

    2012-07-01

    Full Text Available Abstract Background Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT are considered. Methods/design The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy followed by surgery and IORT (10–12 Gy in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. Discussion The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. Trial registration NCT01566123

  16. Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer.

    Science.gov (United States)

    Fucikova, Jitka; Podrazil, Michal; Jarolim, Ladislav; Bilkova, Pavla; Hensler, Michal; Becht, Etienne; Gasova, Zdenka; Klouckova, Jana; Kayserova, Jana; Horvath, Rudolf; Fialova, Anna; Vavrova, Katerina; Sochorova, Klara; Rozkova, Daniela; Spisek, Radek; Bartunkova, Jirina

    2018-01-01

    Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population. The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively. No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment. Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

  17. Fluosol and oxygen breathing as an adjuvant to radiation therapy in the treatment of locally advanced non-small cell carcinoma of the lung: Results of a phase I/II study

    International Nuclear Information System (INIS)

    Lustig, R.; Lowe, N.; Prosnitz, L.; Spaulding, M.; Cohen, M.; Stitt, J.; Brannon, R.

    1990-01-01

    Fluosol, a perflourcarbon emulsion, has the ability to carry oxygen in solution. In conjunction with oxygen breathing and radiation, fluosol has been shown in animal models to enhance local tumor control. In September 1985, a Phase I/II Study was instituted to evaluate the effect of this adjuvant therapy with radiation in non-small cell carcinomas of the lung. Of the 49 patients administered Fluosol, 34 mild moderate adverse reactions were noted in 22 patients to either the test dose/infusion or post infusion. Flushing, dyspnea and hypertension and chills and/or fever were the typical symptoms. Transient elevation of blood chemistries were noted in some patients. Six patients had transient depression of WBC counts and two patients had transient depression of platelets. None of these altered treatment. Forty-five patients received Fluosol of which 34 completed the planned therapy. Six patients were diagnosed with metastatic disease during therapy and three patients died of their disease during treatment. Radiation therapy was administered at a daily fraction of 165 to 200 cGy per fraction to a total dose of 5940 to 6800 cGy

  18. Expression and immunogenicity of NY-ESO-1 in colorectal cancer.

    Science.gov (United States)

    Li, Ya; Song, Ruifeng; Li, Xinqiang; Xu, Feng

    2017-06-01

    Serum assays of NY-ESO-1 antibodies provide a guide to discriminate between patients who suffer from different types of cancer. In the present study, the expression of NY-ESO-1 was detected with the aim to identify a novel tumor antigen in colorectal cancer (CRC). Sera were obtained from 89 healthy individuals and 236 patients with CRC with stage I, II, III and IV tumors. The NY-ESO-1 autoantibody levels were determined using an enzyme-linked immunosorbent assay. The mRNA and protein expression levels of NY-ESO-1 were detected using reverse transcription-polymerase chain reaction and immunohistochemistry, respectively, in 60 CRC and paired adjacent non-tumor tissues. NY-ESO-1 antibody was detected in 40 of the 236 (16.9%) patients with CRC. The NY-ESO-1 antibody combined with carcinoembryonic antigen enhanced the sensitivity, from 52.1 to 62.7%, of the diagnosis of CRC. The frequency of antibody positivity increased with the TNM cancer stage (8.8 vs. 28.3% in stages I+II and III+IV, respectively). The mRNA and protein expression levels of NY-ESO-1 were significantly higher in CRC tissue than in adjacent non-tumor tissue. In conclusion, NY-ESO-1 is frequently expressed in CRC with the capacity of inducing a humoral immune response in CRC patients, exhibiting the potential to be a promising biomarker for CRC.

  19. EFECTO DEL CONTENIDO DE CARBONO SOBRE LA RESISTENCIA AL DESGASTE ABRASIVO DE RECUBRIMIENTOS DE CrC DEPOSITADOS POR PULVERIZACIÓN CATÓDICA MAGNETRÓN EFEITO DO CONTEÚDO DE CARBONO SOBRE A RESISTÊNCIA AO DESGASTE ABRASIVO DE RECOBRIMENTOS DE CrC DEPOSITADOS POR PULVERIZAÇÃO CATÓDICA MAGNETRÃO EFFECT OF THE CARBON CONTENT IN ABRASIVE WEAR RESISTANCE OF CrC COATINGS DEPOSITED BY MAGNETRON SPUTTERING

    Directory of Open Access Journals (Sweden)

    Maryory Astrid Gómez

    2012-12-01

    Full Text Available Los recubrimientos de carburo de cromo sobre acero son un buen candidato para aplicaciones de conformado y moldes de inyección. La alta resistencia mecánica, resistencia química y estabilidad a alta temperatura de la fase Cr3C2 pueden ser compatibles con el intenso desgaste abrasivo y la corrosión en tales operaciones de fabricación. En este trabajo se depositaron recubrimientos de CrC por pulverización catódica magnetrón RF, los cuales mostraron contenidos de carbono entre el 25 % y el 58 % por análisis EDS. Los valores de dureza de estos recubrimientos fueron entre 15 y 24 GPa; los más duros de las muestras tuvieron contenido de carbono en el rango de 39-53 %. El desgaste abrasivo de los recubrimientos se evaluó utilizando un equipo de disco abrasivo con polvo de diamante. El volumen de las huellas de abrasión se midió con las imágenes obtenidas en el microscopio interferométrico y además se corroboró con el cálculo del volumen geométrico basado en secciones medidas con el perfilómetro. El comportamiento al desgaste abrasivo mostró una marcada dependencia con el contenido de carbono. El desgaste abrasivo más bajo se obtuvo para los recubrimientos con el más alto contenido de carbono.Os recobrimentos de carburo de cromo sobre aço são um bom candidato para aplicações de conformado e moldes de injeção. A alta resistência mecânica, resistência química e estabilidade em alta temperatura da fase Cr3C2 podem ser compatíveis com o intenso desgaste abrasivo e a corrosão em tais operações de fabricação. Neste trabalho depositaram-se recobrimentos de CrC por pulverização catódica magnetrão RF, os quais mostraram conteúdos de carbono entre 25 % e 58 % por análise EDS. Os valores de dureza destes recobrimentos foram entre 15 e 24 GPa; os mais duros das mostras tiveram conteúdo de carbono na faixa de 39-53 %. O desgaste abrasivo dos recobrimentos avaliou-se utilizando uma equipe de disco abrasivo com pó de

  20. Prognostic value of baseline metabolic tumor volume in early stage Hodgkin's lymphoma in the standard arm of H10 trial

    DEFF Research Database (Denmark)

    Cottereau, Anne Ségolène; Versari, Annibale; Loft, Annika

    2018-01-01

    We tested baseline PET/CT as a measure of total tumor burden in order to better identify high risk patients in early-stage Hodgkin's lymphoma (HL). Stage I-II HL patients enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and inte......We tested baseline PET/CT as a measure of total tumor burden in order to better identify high risk patients in early-stage Hodgkin's lymphoma (HL). Stage I-II HL patients enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET...... and compared to baseline characteristics, staging classifications and iPET2. A total of 258 patients were eligible, 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 PFS and 12 OS events. TMTV was prognosticator of PFS (p... respectively. The 5y-PFS and OS were 71% and 83% in the high TMTV (>147cm3) group (n=46) vs. 92% and 98% in the low TMTV group (≤147cm3). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared to the current staging systems proposed by EORTC/GELA, GHSG, or NCCN groups...

  1. Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality

    DEFF Research Database (Denmark)

    Strömberg, Ulf; Peterson, Stefan; Holmberg, Erik

    2016-01-01

    -specific incidence of CMM. The incidence of stage I-II tumors was higher in the western health care region, whereas the incidence of stage III-IV CMMs was higher in the southern region. The divergent incidence patterns per stage at diagnosis were consistent across population strata based on educational level......Background Preventive measures are needed to counteract the increasing burden of cutaneous malignant melanoma (CMM). As a basis for rational melanoma prevention, we investigated geographic differences and impact from socioeconomic factors related to incidence, clinical stage at diagnosis...... and outcome. Material and methods All patients with primary invasive CMM diagnosed in 2004-2013 in the southern and the western Swedish health care regions with a population of 2.9 million adults were eligible for the study. Population-based data were obtained from the national Cancer Register...

  2. Elevated tumor-to-liver uptake ratio (TLR) from 18F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

    International Nuclear Information System (INIS)

    Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin; Duan, Yinghua; Zhang, Zhanwen; Hu, Ping; Wang, Xiaoyan

    2017-01-01

    The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from 18 F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent 18 F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative 18 F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with elevated TLR. Cox

  3. Elevated tumor-to-liver uptake ratio (TLR) from {sup 18}F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin [6th Affiliated Hospital, Sun Yat-sen University, Department of Colorectal Surgery, Guangzhou, Guangdong (China); Duan, Yinghua [1st Affiliated Hospital, Sun Yat-sen University, Department of Traditional Chinese Medicine, Guangzhou (China); Zhang, Zhanwen; Hu, Ping [6th Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China); Wang, Xiaoyan [1st Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China)

    2017-11-15

    The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from {sup 18}F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent {sup 18}F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative {sup 18}F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with

  4. Clinical phase I/II trial to investigate neoadjuvant intensity-modulated short term radiation therapy (5 × 5 gy and intraoperative radiation therapy (15 gy in patients with primarily resectable pancreatic cancer - NEOPANC

    Directory of Open Access Journals (Sweden)

    Roeder Falk

    2012-03-01

    Full Text Available Abstract Background The current standard treatment, at least in Europe, for patients with primarily resectable tumors, consists of surgery followed by adjuvant chemotherapy. But even in this prognostic favourable group, long term survival is disappointing because of high local and distant failure rates. Postoperative chemoradiation has shown improved local control and overalls survival compared to surgery alone but the value of additional radiation has been questioned in case of adjuvant chemotherapy. However, there remains a strong rationale for the addition of radiation therapy considering the high rates of microscopically incomplete resections after surgery. As postoperative administration of radiation therapy has some general disadvantages, neoadjuvant and intraoperative approaches theoretically offer benefits in terms of dose escalation, reduction of toxicity and patients comfort especially if hypofractionated regimens with highly conformal techniques like intensity-modulated radiation therapy are considered. Methods/Design The NEOPANC trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant short course intensity-modulated radiation therapy (5 × 5 Gy in combination with surgery and intraoperative radiation therapy (15 Gy, followed by adjuvant chemotherapy according to the german treatment guidelines, in patients with primarily resectable pancreatic cancer. The aim of accrual is 46 patients. Discussion The primary objectives of the NEOPANC trial are to evaluate the general feasibility of this approach and the local recurrence rate after one year. Secondary endpoints are progression-free survival, overall survival, acute and late toxicity, postoperative morbidity and mortality and quality of life. Trial registration NCT01372735.

  5. Fatigue crack growth in mixed mode I+III+III non proportional loading conditions in a 316 stainless steel, experimental analysis and modelization of the effects of crack tip plasticity

    International Nuclear Information System (INIS)

    Fremy, F.

    2012-01-01

    This thesis deals with fatigue crack growth in non-proportional variable amplitude mixed mode I + II + III loading conditions and analyses the effects of internal stresses stemming from the confinement of the plastic zone in small scale yielding conditions. The tests showed that there are antagonistic long-distance and short-distance effects of the loading history on fatigue crack growth. The shape of loading path, and not only the maximum and minimum values in this path, is crucial and, by comparison, the effects of contact and friction are of lesser importance. Internal stresses play a major role on the fatigue crack growth rate and on the crack path. An approach was developed to analyze the elastic-plastic behavior of a representative section of the crack front using the FEA. A model reduction technic is used to extract the relevant information from the FE results. To do so, the velocity field is partitioned into mode I, II, III elastic and plastic components, each component being characterized by an intensity factor and a fixed spatial distribution. The calculations were used to select seven loading paths in I + II and I + II + III mixed mode conditions, which all have the same amplitudes for each mode, the same maximum, minimum and average values. These paths are supposed to be equivalent in the sense of common failure criteria, but differ significantly when the elastic-plastic behavior of the material is accounted for. The results of finite element simulations and of simulations using a simplified model proposed in this thesis are both in agreement with experimental results. The approach was also used to discuss the role of mode III loading steps. Since the material behavior is nonlinear, the nominal loading direction does not coincide with the plastic flow direction. Adding a mode III loading step in a mode I+II fatigue cycle, may, in some cases, significantly modify the behaviour of the crack (crack growth rate, crack path and plastic flow). (author)

  6. Phase I-II study of two consecutive courses of high-dose epipodophyllotoxin, ifosfamide, and carboplatin with autologous bone marrow transplantation for treatment of adult patients with solid tumors.

    Science.gov (United States)

    Lotz, J P; Machover, D; Malassagne, B; Hingh, B; Donsimoni, R; Gumus, Y; Gerota, J; Lam, Y; Tulliez, M; Marsiglia, H

    1991-10-01

    We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8+, 27+, and 37+ months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy.

  7. Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety.

    Science.gov (United States)

    Ido, Akio; Moriuchi, Akihiro; Numata, Masatsugu; Murayama, Toshinori; Teramukai, Satoshi; Marusawa, Hiroyuki; Yamaji, Naohisa; Setoyama, Hitoshi; Kim, Il-Deok; Chiba, Tsutomu; Higuchi, Shuji; Yokode, Masayuki; Fukushima, Masanori; Shimizu, Akira; Tsubouchi, Hirohito

    2011-05-08

    Hepatocyte growth factor (HGF) stimulates hepatocyte proliferation, and also acts as an anti-apoptotic factor. Therefore, HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF (rh-HGF), including a phase I/II study of patients with fulminant hepatitis (FH) or late-onset hepatic failure (LOHF), in order to examine the safety, pharmacokinetics, and clinical efficacy of this molecule. Potential adverse effects identified through preclinical safety tests with rh-HGF include a decrease in blood pressure (BP) and an increase in urinary excretion of albumin. Therefore, we further investigated the effect of rh-HGF on circulatory status and renal toxicity in preclinical animal studies. In a clinical trial, 20 patients with FH or LOHF were evaluated for participation in this clinical trial, and four patients were enrolled. Subjects received rh-HGF (0.6 mg/m2/day) intravenously for 12 to 14 days. We established an infusion method to avoid rapid BP reduction in miniature swine, and confirmed reversibility of renal toxicity in rats. Although administration of rh-HGF moderately decreased BP in the participating subjects, this BP reduction did not require cessation of rh-HGF or any vasopressor therapy; BP returned to resting levels after the completion of rh-HGF infusion. Repeated doses of rh-HGF did not induce renal toxicity, and severe adverse events were not observed. Two patients survived, however, there was no evidence that rh-HGF was effective for the treatment of FH or LOHF. Intravenous rh-HGF at a dose of 0.6 mg/m2 was well tolerated in patients with FH or LOHF; therefore, it is desirable to conduct further investigations to determine the efficacy of rh-HGF at an increased dose.

  8. Safety and immunogenicity of an inactivated cell culture-derived H7N9 influenza vaccine in healthy adults: A phase I/II, prospective, randomized, open-label trial.

    Science.gov (United States)

    Wu, Un-In; Hsieh, Szu-Min; Lee, Wen-Sen; Wang, Ning-Chi; Kung, Hsiang-Chi; Ou, Tsong-Yih; Chen, Fu-Lun; Lin, Te-Yu; Chen, Yee-Chun; Chang, Shan-Chwen

    2017-07-24

    We conducted a phase I/II clinical trial to evaluate the safety and immunogenicity of a Madin-Darby canine kidney (MDCK) cell-grown inactivated H7N9 influenza vaccine for pandemic preparedness purposes. Between April 7, 2015 and May 27, 2016, healthy adults aged 20-60years were enrolled sequentially in phase I (n=40) and phase II (n=160) from three hospitals in Taiwan and randomized to receive 2 doses of whole-virus H7N9 vaccine (15 or 30μg hemagglutinin antigen (HA) with or without an aluminum hydroxide adjuvant) at 21-day intervals. Safety up to 180days and changes in hemagglutinin inhibition (HI) titers at 21days after each vaccination were determined. Of the 200 randomized subjects, 193 (96.5%) received 2 doses of the study vaccine and were included in the intention-to-treat analysis for safety, and 190 (95%) were included in the per-protocol analysis for immunogenicity. Most adverse events were mild and transient; no death or vaccine-related serious adverse events were reported. Overall, higher immune responses were observed in the groups administered with 30μgHA formulation than in the other two groups administered with 15μgHA formulation. The highest immune response was observed in subjects who received 2 doses of the adjuvanted vaccine containing 30μgHA with HI titer, seroprotection rate, seroconversion rate, and seroconversion factor of 36.2, 64.6%, 64.6% and 5.7, respectively. Our study demonstrated that the H7N9 influenza vaccine containing 30µgHA with aluminum hydroxide adjuvant was immunogenic and safe in adults aged 20-60years. CLINICALTRIALS.GOV identifier: NCT02436928. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

    Directory of Open Access Journals (Sweden)

    Weis Christine

    2010-07-01

    Full Text Available Abstract Background Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed. Methods/Design This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part® Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10 days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10 days and 3 months (±14 days after surgery. Discussion This trial aims to assess, whether the intra-peritoneal application of A-Part® Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls. Trial registration NCT00646412

  10. Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety

    Directory of Open Access Journals (Sweden)

    Setoyama Hitoshi

    2011-05-01

    Full Text Available Abstract Background Hepatocyte growth factor (HGF stimulates hepatocyte proliferation, and also acts as an anti-apoptotic factor. Therefore, HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF (rh-HGF, including a phase I/II study of patients with fulminant hepatitis (FH or late-onset hepatic failure (LOHF, in order to examine the safety, pharmacokinetics, and clinical efficacy of this molecule. Methods Potential adverse effects identified through preclinical safety tests with rh-HGF include a decrease in blood pressure (BP and an increase in urinary excretion of albumin. Therefore, we further investigated the effect of rh-HGF on circulatory status and renal toxicity in preclinical animal studies. In a clinical trial, 20 patients with FH or LOHF were evaluated for participation in this clinical trial, and four patients were enrolled. Subjects received rh-HGF (0.6 mg/m2/day intravenously for 12 to 14 days. Results We established an infusion method to avoid rapid BP reduction in miniature swine, and confirmed reversibility of renal toxicity in rats. Although administration of rh-HGF moderately decreased BP in the participating subjects, this BP reduction did not require cessation of rh-HGF or any vasopressor therapy; BP returned to resting levels after the completion of rh-HGF infusion. Repeated doses of rh-HGF did not induce renal toxicity, and severe adverse events were not observed. Two patients survived, however, there was no evidence that rh-HGF was effective for the treatment of FH or LOHF. Conclusions Intravenous rh-HGF at a dose of 0.6 mg/m2 was well tolerated in patients with FH or LOHF; therefore, it is desirable to conduct further investigations to determine the efficacy of rh-HGF at an increased dose.

  11. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II).

    Science.gov (United States)

    Lamo-Espinosa, José M; Mora, Gonzalo; Blanco, Juan F; Granero-Moltó, Froilán; Nuñez-Córdoba, Jorge M; Sánchez-Echenique, Carmen; Bondía, José M; Aquerreta, Jesús Dámaso; Andreu, Enrique J; Ornilla, Enrique; Villarón, Eva M; Valentí-Azcárate, Andrés; Sánchez-Guijo, Fermín; Del Cañizo, María Consuelo; Valentí-Nin, Juan Ramón; Prósper, Felipe

    2016-08-26

    Mesenchymal stromal cells are a promising option to treat knee osteoarthritis. Their safety and usefulness must be confirmed and the optimal dose established. We tested increasing doses of bone marrow mesenchymal stromal cells (BM-MSCs) in combination with hyaluronic acid in a randomized clinical trial. A phase I/II multicenter randomized clinical trial with active control was conducted. Thirty patients diagnosed with knee OA were randomly assigned to intraarticularly administered hyaluronic acid alone (control), or together with 10 × 10(6) or 100 × 10(6) cultured autologous BM-MSCs, and followed up for 12 months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. No adverse effects were reported after BM-MSC administration or during follow-up. BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value (IQR) for control, low-dose and high-dose groups change from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 4 (3, 5), 2 (1, 3) and 2 (0,4) respectively at 12 months (low-dose vs control group p = 0.005 and high-dose vs control group p injection of in vitro expanded autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when 100 × 10(6) cells are administered. These results pave the way for a future phase III clinical trial. gov identifier NCT02123368. Nº EudraCT: 2009-017624-72.

  12. Safety, pharmacokinetics and efficacy of factor VIIa formulated with PEGylated liposomes in haemophilia A patients with inhibitors to factor VIII--an open label, exploratory, cross-over, phase I/II study.

    Science.gov (United States)

    Spira, J; Plyushch, O; Zozulya, N; Yatuv, R; Dayan, I; Bleicher, A; Robinson, M; Baru, M

    2010-11-01

      Recombinant activated factor VIIa (FVIIa) is a bypassing agent used to treat bleeding episodes in haemophilia patients with inhibitors to factor VIII (FVIII) and factor IX. The pharmacological effect of FVIIa is short-lived and therefore with the recommended dose of 90 μg kg(-1), a bleeding episode is treated with multiple injections. A long-acting form of FVIIa that can ensure adequate haemostasis with a single infusion, without increasing the thrombotic risk, would therefore be beneficial. PEGylated liposomes (PEGLip) have been shown to bind FVIIa and to improve haemostatic efficacy in preclinical experiments. In the present phase I/II clinical trial, we assessed the safety and efficacy of PEGLip-formulated FVIIa in severe haemophilia A patients (FVIII≤1%) with inhibitors to FVIII. Each patient received one prophylactic infusion of standard FVIIa and one prophylactic infusion of PEGLip-formulated FVIIa. The order of the infusions was randomized and the two infusions were separated by a ten-day washout period. Efficacy assessed by thromboelastography revealed that PEGLip-FVIIa induced significantly shorter clotting times and produced higher clot firmnesses than standard FVIIa. Thrombin generation assays showed that PEGLip-FVIIa induced faster thrombin generation and higher peak levels of thrombin than standard FVIIa. These effects lasted up to 5 h postinfusion. Measurements of D-dimer, prothrombin fragment 1+2 and fibrinogen showed no significant differences between the PEGLip-FVIIa and standard FVIIa treatments. PEGLip-FVIIa therefore showed improved haemostatic efficacy without increased risk of thrombosis and may be further developed for the treatment for bleeding episodes in haemophilia patients with inhibitors. © 2010 Blackwell Publishing Ltd.

  13. Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

    Science.gov (United States)

    Fayad, Luis; Offner, Fritz; Smith, Mitchell R.; Verhoef, Gregor; Johnson, Peter; Kaufman, Jonathan L.; Rohatiner, Ama; Advani, Anjali; Foran, James; Hess, Georg; Coiffier, Bertrand; Czuczman, Myron; Giné, Eva; Durrant, Simon; Kneissl, Michelle; Luu, Kenneth T.; Hua, Steven Y.; Boni, Joseph; Vandendries, Erik; Dang, Nam H.

    2013-01-01

    Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. Results In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. Conclusion R-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20+/CD22+ B-cell NHL. PMID:23295790

  14. Regional nodal relapse in surgically staged Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Hoeller, Ulrike; Mueller, Thomas; Schubert, Tina; Budach, Volker; Ghadjar, Pirus; Brenner, Winfried; Kiecker, Felix; Schicke, Bernd; Haase, Oliver

    2015-01-01

    The nodal relapse pattern of surgically staged Merkel cell carcinoma (MCC) with/without elective nodal radiotherapy (RT) was studied in a single institution. A total of 51 patients with MCC, 33 % UICC stage I, 14 % II, 53 % III (4 lymph node metastases of unknown primary) were eligible. All patients had surgical staging: 23 patients sentinel node biopsy (SNB), 22 patients SNB followed by lymphadenectomy (LAD) and 6 patients LAD. In all, 94 % of the primary tumors (PT) were completely resected; 57 % of patients received RT, 51 % of known PT sites, 33 % (8/24 patients) regional RT to snN0 nodes and 68 % (17/27 patients) to pN+ nodes, mean reference dose 51.5 and 50 Gy, respectively. Mean follow-up was 6 years (range 2-14 years). A total of 22 % (11/51) patients developed regional relapses (RR); the 5-year RR rate was 27 %. In snN0 sites (stage I/II), relapse occurred in 5 of 14 nonirradiated vs. none of 8 irradiated sites (p = 0.054), resulting in a 5-year RR rate of 33 % versus 0 % (p = 0.16). The crude RR rate was lower in stage I (12 %, 2/17 patients) than for stage II (43 %, 3/7 patients). In stage III (pN+), RR appeared to be less frequent in irradiated sites (18 %, 3/14 patients) compared with nonirradiated sites (33 %, 3/10 patients, p = 0.45) with 5-year RR rates of 23 % vs. 34 %, respectively. Our data suggest that adjuvant nodal RT plays a major role even if the sentinel nodes were negative. Adjuvant RT of the lymph nodes in patients with stage IIa tumors and RT after LAD in stage III tumors is proposed and should be evaluated prospectively. (orig.) [de

  15. Efficacy and Safety of Regorafenib With 2/1 Schedule for Patients ≥ 75 Years With Metastatic Colorectal Cancer (mCRC) After Failure of 2 Lines of Chemotherapy.

    Science.gov (United States)

    Petrioli, Roberto; Chirra, Martina; Messuti, Luciana; Fiaschi, Anna Ida; Savelli, Vinno; Martellucci, Ignazio; Francini, Edoardo

    2018-02-21

    In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC. Patients ≥ 75 years with mCRC who progressed after oxaliplatin- and irinotecan-based chemotherapy received regorafenib on a 2/1 schedule. Potentially frail subjects were identified by G8 screening tool and excluded. The 2-month disease-control rate was the primary endpoint, and the secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and objective response rate. Between February 2014 and May 2017, 23 patients with mCRC were recruited at our institution. No partial or complete responses were observed, and the stable disease and disease-control rate were 52.2%. The median PFS was 4.8 months (95% confidence interval, 3.8-6.3 months), and the median OS was 8.9 months (95% confidence interval, 6.9-10.6 months). Adverse events were uncommon, and the most frequent grade 3 toxicity adverse events were hand-foot skin reaction (9%) and fatigue (9%). Toxicity-related dose reductions and discontinuations occurred in 5 and 2 patients, respectively. Regorafenib administered with a modified 2/1 schedule to patients who were aged ≥ 75 years and non-frail with treatment-refractory mCRC seems to be tolerable and achieve encouraging results in terms of PFS and OS. Copyright © 2018. Published by Elsevier Inc.

  16. Understanding cancer staging

    Science.gov (United States)

    ... detailed information about the cancer stage. TNM Staging System The most common system for staging cancer in the form of solid tumor is the TNM system. Most providers and cancer centers use it to stage ...

  17. Clinical significance of Fusobacterium nucleatum, epithelial–mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Yan X

    2017-10-01

    Full Text Available Xuebing Yan,1,* Liguo Liu,2,* Hao Li,1,* Huanlong Qin,1 Zhenliang Sun1,3 1Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 2Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 3Central Laboratory, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, South Campus, Shanghai, China *These authors contributed equally to this work Abstract: Colorectal cancer (CRC is a common digestive malignancy and emerging studies have closely linked its initiation and development with gut microbiota changes. Fusobacterium nucleatum (Fn has been recently identified as a pathogenic bacteria for CRC; however, its prognostic significance for patients is poorly investigated and is less for patients within late stage. Therefore, in this study, we made efforts to analyze its level and prognostic significance in a retrospective cohort of 280 stage III/IV CRC patients. We found that the Fn level was abnormally high in tumor tissues and correlated with tumor invasion, lymph node metastasis status, and distant metastasis. We also identified it as an independent adverse prognostic factor for cancer-specific survival (CSS and disease-free survival (DFS. The following subgroup analysis indicated that Fn level could stratify CSS and DFS in stage IIIB/C and IV patients but failed in stage IIIA patients. In addition, stage III/IV patients with low Fn level were found to benefit more from adjuvant chemotherapy than those with high Fn level, in terms of DFS. Finally, we analyzed the expression and clinical significance of epithelial-to-mesenchymal transition (EMT markers (E-cadherin and N-cadherin and cancer stem cell (CSC markers (Nanog, Oct-4, and Sox-2 in CRC tissues. The results indicated that N-cadherin, Nanog, Oct-4, and Sox-2 were adverse prognostic factors in these patients, while the opposite was true for E-cadherin. More importantly, expression of E

  18. Fluorouracil combined with the pure (6S)-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma: a phase I-II study.

    Science.gov (United States)

    Machover, D; Grison, X; Goldschmidt, E; Zittoun, J; Lotz, J P; Metzger, G; Richaud, J; Hannoun, L; Marquet, J; Guillot, T

    1992-03-04

    Potentiation of the antitumor activity of fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase, fluorodeoxyuridine monophosphate, and methylene tetrahydrofolate, which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C-6 carbon of the pteridine ring. Only the levorotatory (6S)-stereoisomer of folinic acid is transformed into active folate cofactors. However, the (6R)-stereoisomer of folinic acid is not inert; it was shown to interfere with the (6S) form at the cellular level. The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out a phase I-II study of 5-FU combined with the (6S)-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. We also determined the plasma pharmacokinetics of folates after intravenous (IV) injection of (6S)-folinic acid at the dose used in this study. Treatment consisted of 5-FU (350-550 mg/m2 per day by IV infusion for 2 hours) and (6S)-folinic acid (100 mg/m2 per day by IV bolus injection) given for 5 consecutive days; the treatment was repeated every 21 days. Twenty-five patients with advanced colorectal carcinoma, who had had no prior chemotherapy, were evaluated for antitumor activity. The quantity of folates in plasma was measured using a microbiological assay. The median follow-up time was 9 months (range, 3.5-15.2 months). The response rate was 52% (complete response, 12%; partial response, 40%). The median time to disease progression for responding patients was 9.2 months (range, 5.9-15+ months). The estimated probability of survival at 12 months was 73%. Palliative improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects were grade 3 diarrhea, dermatitis, and oral mucositis. Grade 4 toxicity did not occur. Myeloid toxicity was minor. After IV injection, (6S)-folinic acid was rapidly cleared from plasma (mean half-lives: alpha = 7.2 minutes and beta = 126 minutes). The mean concentration of the unchanged compound 2 hours after injection was 5.8 mumol/L. The (6S)-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. Our results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines.

  19. Comparison of neurological and functional outcomes after administration of granulocyte-colony-stimulating factor in motor-complete versus motor-incomplete postrehabilitated, chronic spinal cord injuries: a phase I/II study.

    Science.gov (United States)

    Saberi, Hooshang; Derakhshanrad, Nazi; Yekaninejad, Mir Saeed

    2014-01-01

    Granulocyte-colony-stimulating factor (G-CSF) is a major growth factor in the activation and differentiation of granulocytes. This cytokine has been widely and safely employed in different disease conditions over many years. The administration of the growth factors in spinal cord injury (SCI) has been reported elsewhere; here we have tried to see the effect of SCI severity on the neurological outcomes after neuroprotective treatment for SCI with G-CSF. Seventy-four consecutive patients with SCI of at least 6 months' duration, with stable neurological status in the last 3 months, having informed consent for the treatment were included in the study. All the patients had undergone at least 3 months of standard rehabilitation. Patients were assessed by the American Spinal Injury Association (ASIA) scale, Spinal Cord Independence Measure (SCIM) III, and International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) just before intervention and periodically until 6 months after subcutaneous administration of 5 µg/kg per day of G-CSF for 7 consecutive days. Multiple linear regression models were performed for statistical evaluation of lesion completeness and level of injury on changes in ASIA motor, light touch, pinprick, IANR-SCIFRS, and SCIM III scores, as a phase I/II comparative study. The study consisted of 52 motor-complete and 22 motor-incomplete SCI patients. There was no significant difference regarding age and sex, chronicity, and level of SCI between the two groups. Motor-incomplete patients had significantly more improvement in ASIA motor score compared to the motor-complete patients (7.68 scores, p scores, p = 0.003) and pinprick sensory scores (4.89 scores, p = 0.011). Therefore, G-CSF administration in motor-incomplete SCIs is associated with significantly higher motor improvement, and also the higher the initial ASIA Impairment Scale (AIS) grade, the less would be the final AIS change, and incomplete cases are more welcome into the future studies. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

  20. Daidzein plus isolase associated with zinc improves clinical symptoms and quality of life in patients with LUTS due to benign prostatic hyperplasia: Results from a phase I-II study

    Directory of Open Access Journals (Sweden)

    Daniele Tiscione

    2017-03-01

    Full Text Available Objective: In the last years there is a growing interest in nutraceutical substances that seems able to improve clinical symptoms in patients with lower urinary tract symptoms (LUTS due to benign prostatic hyperplasia (BPH. In this paper, we evaluated both efficacy and safety of a combination of daidzein with isolase and zinc in patients with LUTS due to BPH. Materials and methods: In a phase I-II study clinical trial we enrolled patients with clinical and instrumental diagnosis of LUTS associated to BPH that received a six-month treatment with a combination of daidzein with isolase and zinc (1 tablet/day. Clinical, laboratory and instrumental analyses were carried out at the time of admission (T0 and 6 months after the ending of the treatment (T1. The Italian version of International Prostatic Symptom Score (IPSS, International Index of Erectile Function (IIEF-5 and Quality of Well-Being (QoL questionnaires were used. The development of adverse drug reactions (ADRs and drug interactions (DDIs were recorded using the Naranjo scale and drug interaction probability scale. Student’s t test and Anova test were used for statistical analysis, and the threshold of statistical significance was set at P < 0.05. Results: We enrolled 71 patients, 62 (87.3% completed the follow-up and we documented a significant differences between T0 and T1 in terms of IPSS [21.5 ± 1.2 vs 16.2 ± 1.5; (-4.8; p < 0.001], Cmax [9.7 ± 3.7 vs 15.3 ± 2.5; (+5.6; p < 0.001] and QoL [0.56 ± 0.15 vs 0.84 ± 0.19; (+0.28; p < 0.001]. In contrast, no significant difference were recorded in terms of IIEF-5 [p = 0.50] and PSA [p = 0.67]. Finally, we did not record any significant ADRs or DDIs during the study. Conclusions: In this study, we documented that a combination of daidzein with isolase and zinc, reduces the clinical symptoms of LUTS and improves the quality of life in patients with BPH, without the development of ADRs or DDIs.

  1. Radioimmunotherapy of small cell lung carcinoma with the two-step method using a bispecific anti-carcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid (DTPA) antibody and iodine-131 Di-DTPA hapten: results of a phase I/II trial.

    Science.gov (United States)

    Vuillez, J P; Kraeber-Bodéré, F; Moro, D; Bardiès, M; Douillard, J Y; Gautherot, E; Rouvier, E; Barbet, J; Garban, F; Moreau, P; Chatal, J F

    1999-10-01

    As small cell lung carcinoma (SCLC) is frequently a widespread disease at diagnosis, highly radiosensitive and often only partially responsive to chemotherapy, radioimmunotherapy (RIT) would appear to be a promising technique for treatment. We report the preliminary results of a Phase I/II trial of RIT in SCLC using a two-step method and a myeloablative protocol with circulating stem cells transplantation. Fourteen patients with proved SCLC relapse after chemotherapy were treated with RIT. They were first injected i.v. with a bispecific (anti-carcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid) monoclonal antibody (20-80 mg in 100 ml of saline solution) and then 4 days later with di-(In-diethylenetriaminepentaacetic acid)-tyrosyl-lysine hapten labeled with 1.48-6.66 GBq (40-180 mCi) of I-131 and diluted in 100 ml of saline solution. In patients receiving 150 mCi or more, circulating stem cells were harvested before treatment and reinfused 10-15 days later. Treatment response was evaluated by CT and biochemical data during the month before and 1, 3, 6, and 12 months after treatment. All patients received the scheduled dose without immediate adverse reactions to bispecific antibody or 1-131 hapten. Toxicity was mainly hematological, with two cases of grade 2 leukopenia and three cases of grade 3 or 4 thrombopenia. Body scanning 8 days after injection of the radiolabeled hapten generally showed good uptake at the tumor sites. Estimated tumor dose was 2.6-32.2 cGy/mCi. Among the 12 patients evaluated to date, we have observed 9 progressions, 2 partial responses (one almost complete for 3 months), and 1 stabilization of more than 24 months. Efficiency and toxicity were dose-related. The maximal tolerable dose without hematological rescue was 150 mCi. These preliminary results are encouraging, and dose escalation is currently continuing to reach 300 mCi. RIT should prove to be an interesting therapeutic method for SCLC, although repeated injections and hematological rescue will probably be required, as well as combination with other treatment modalities.

  2. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

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    Chongsheng Qian

    2017-05-01

    Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT, the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB. Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9% or a third party haploidentical donor (57.1%. One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%. Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered.

  3. Phase I/II trials of {sup 186}Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival

    Energy Technology Data Exchange (ETDEWEB)

    Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Divoli, Antigoni; Flux, Glenn D. [The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, Joint Department of Physics, London (United Kingdom); Dearnaley, David P.; Johnson, Bernadette [The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, Division of Radiotherapy and Imaging, London (United Kingdom); O' Sullivan, Joe M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom); McCready, V.R. [Brighton and Sussex University Hospitals NHS Trust, Department of Nuclear Medicine, Brighton (United Kingdom); Du, Yong [The Royal Marsden Hospital NHS Foundation Trust, Department of Nuclear Medicine and PET/CT, London (United Kingdom)

    2017-04-15

    To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit. Clinical data from 57 patients who received 2.5-5.1 GBq of {sup 186}Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed. Whole-body and SPECT-based absorbed doses to the whole body and bone lesions were calculated for 22 patients receiving 5 GBq. The patient mean absorbed dose was defined as the mean of all bone lesion-absorbed doses in any given patient. Kaplan-Meier curves, log-rank tests, Cox's proportional hazards model and Pearson's correlation coefficients were used for overall survival (OS) and correlation analyses. A statistically significantly longer OS was associated with administered activities above 3.5 GBq in the 57 patients (20.1 vs 7.1 months, hazard ratio: 0.39, 95 % CI: 0.10-0.58, P = 0.002). A total of 379 bone lesions were identified in 22 patients. The mean of the patient mean absorbed dose was 19 (±6) Gy and the mean of the whole-body absorbed dose was 0.33 (±0.11) Gy for the 22 patients. The patient mean absorbed dose (r = 0.65, P = 0.001) and the whole-body absorbed dose (r = 0.63, P = 0.002) showed a positive correlation with disease volume. Significant differences in OS were observed for the univariate group analyses according to disease volume as measured from SPECT imaging of {sup 186}Re-HEDP (P = 0.03) and patient mean absorbed dose (P = 0.01), whilst only the disease volume remained significant in a multivariable analysis (P = 0.004). This study demonstrated that higher administered activities led to prolonged survival and that for a fixed administered activity, the whole-body and patient mean absorbed doses correlated with the extent of disease, which, in turn, correlated with survival. This study shows the importance of patient stratification to establish absorbed dose-response correlations and indicates the potential to individualise treatment of bone metastases with radiopharmaceuticals according to patient-specific imaging and dosimetry. (orig.)

  4. Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

    Science.gov (United States)

    Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

    2017-11-17

    Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

  5. Soluble HLA-G is a differential prognostic marker in sequential colorectal cancer disease stages.

    Science.gov (United States)

    Kirana, Chandra; Ruszkiewicz, Andrew; Stubbs, Richard S; Hardingham, Jennifer E; Hewett, Peter J; Maddern, Guy J; Hauben, Ehud

    2017-06-01

    The expression of HLA-G by tumour cells is an established mechanism to escape recognition and immune mediated destruction, allowing tumour survival, growth and metastasis. However, the prognostic value of soluble HLA-G (sHLA-G) remains unknown. Mucinous carcinoma (MC) is a distinct form of colorectal cancer (CRC) found in 10 to 15% of patients, which has long been associated with poor response to treatment. To investigate the prognostic value of plasma sHLA-G levels in CRC patients, preoperative plasma sHLA-G levels were determined by ELISA in CRC patients (n = 133). In addition, the local expression of HLA-G in tumour biopsies was assessed using tissue microarray analysis (n = 255). Within the high 33rd percentile of sHLA-G levels (265-890 U/mL; n = 44) we observed higher frequency of MC patients (p = 0.012; Chi-square), and higher sHLA-G levels in patients with vascular invasion (p = 0.035; two-tailed t-test). Moreover, MC patients had significantly higher sHLA-G levels compared to those with adenocarcinoma not otherwise specified (p = 0.036; two-tailed t-test). Surprisingly, while stage II patients showed negative correlation between sHLA-G levels and liver metastasis free survival (LMFS) (p = 0.041; R = -0.321), in stage III patients high sHLA-G levels were associated with significantly longer LMFS (p = 0.002), and sHLA-G levels displayed positive correlation with LMFS (p = 0.006; R = 0.409). High HLA-G expression in tumours was associated with poor cancer specific overall survival in stage II to III (p = 0.01), and with shorter LMFS in stage II patients (p = 0.004). Our findings reveal that sHLA-G levels are associated with distinct progression patterns in consecutive disease stages, indicating a potential value as surrogate marker in the differential prognosis of CRC. © 2017 UICC.

  6. Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation: indicators of tumor staging and metastasis in adenocarcinomatous sporadic colorectal cancer in Indian population.

    Directory of Open Access Journals (Sweden)

    Rupal Sinha

    Full Text Available Colorectal cancer (CRC development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease.One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed.Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12 and MGMT methylation (p-value <0.049. Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044 and methylated RASSF1A (p-values 0.034, 0.044, FHIT (p-values 0.001, 0.047 and MGMT (p-values 0.018, 0.044 genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025. Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes.Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.

  7. Determinants of morbidity and survival after elective non-curative resection of stage IV colon and rectal cancer.

    Science.gov (United States)

    Kleespies, Axel; Füessl, Kathrin E; Seeliger, Hendrik; Eichhorn, Martin E; Müller, Mario H; Rentsch, Markus; Thasler, Wolfgang E; Angele, Martin K; Kreis, Martin E; Jauch, Karl-Walter

    2009-09-01

    The benefit of elective primary tumor resection for non-curable stage IV colorectal cancer (CRC) remains largely undefined. We wanted to identify risk factors for postoperative complications and short survival. Using a prospective database, we analyzed potential risk factors in 233 patients, who were electively operated for non-curable stage IV CRC between 1996 and 2002. Patients with recurrent tumors, resectable metastases, emergency operations, and non-resective surgery were excluded. Risk factors for increased postoperative morbidity and limited postoperative survival were identified by multivariate analyses. Patients with colon cancer (CC = 156) and rectal cancer (RC = 77) were comparable with regard to age, sex, comorbidity, American Society of Anesthesiologists score, carcinoembryonic antigen levels, hepatic spread, tumor grade, resection margins, 30-day mortality (CC 5.1%, RC 3.9%) and postoperative chemotherapy. pT4 tumors, carcinomatosis, and non-anatomical resections were more common in colon cancer patients, whereas enterostomies (CC 1.3%, RC 67.5%, p 50%, and comorbidity >1 organ. Prognostic factors for limited postoperative survival were hepatic tumor load >50%, pT4 tumors, lymphatic spread, R1-2 resection, and lack of chemotherapy. Palliative resection is associated with a particularly unfavorable outcome in rectal cancer patients presenting with a locally advanced tumor (pT4, expected R2 resection) or an extensive comorbidity, and in all CRC patients who show a hepatic tumor load >50%. For such patients, surgery might be contraindicated unless the tumor is immediately life-threatening.

  8. Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced-stage colorectal cancer.

    Science.gov (United States)

    Wang, Lisha; Liu, Zebing; Fisher, Kurt W; Ren, Fei; Lv, Jiaojie; Davidson, Darrell D; Baldridge, Lee A; Du, Xiang; Cheng, Liang

    2018-01-01

    Current prognostic indicators are ineffective for identifying advanced-stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P=.001) and higher Ki-67 labeling index (LI) (P=.031). The tumor Ki-67 LI was high (≥20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P=.031), positive p53 expression (P=.031), and negative PD-L1 expression (P=.003). The 5-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P<.001). In univariate analysis, negative p53 (P=.001), low Ki-67 LI (P=.006), low PD-L1 expression (P=.044), low TNM stage (P<.001), rectosigmoid location (P=.026), and small size (P=.013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34-4.59, P=.004), high Ki-67 LI (HR, 2.62; 95% CI, 1.12-6.14, P=.027) and high TNM stage (HR, 2.598; 95% CI, 1.55-4.37, P<.001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score ≥35 and Ki-67 LI ≥20% identifies patients with poor clinical outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Prostate cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000397.htm Prostate cancer staging To use the sharing features on this ... trials you may be able to join How Prostate Cancer Staging is Done Initial staging is based on ...

  10. Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease.

    Science.gov (United States)

    Murphy, Caitlin C; Sanoff, Hanna K; Stitzenberg, Karyn B; Baron, John A; Lund, Jennifer L; Sandler, Robert S

    2017-01-01

    Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 ( n = 6, 862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age age 50-69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50-69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years.

  11. Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

    Directory of Open Access Journals (Sweden)

    Caitlin C. Murphy

    2017-01-01

    Full Text Available Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC in younger (age < 50 populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute’s Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n=6,862. Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50 and older (age 50–69, age ≥ 70 CRC patients. Results. Younger patients were more likely to be black (13% and Hispanic (15% than patients aged 50–69 years (11% and 10%, resp. and ≥70 years (7% each. A larger proportion of young white (41% and Hispanic (33% patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%. The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%. Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years.

  12. Validation of the ICON-S staging for HPV-associated oropharyngeal carcinoma using a pre-defined treatment policy.

    Science.gov (United States)

    Porceddu, Sandro V; Milne, Rob; Brown, Elizabeth; Bernard, Anne; Rahbari, Reza; Cartmill, Bena; Foote, Matthew; McGrath, Margaret; Coward, Jermaine; Panizza, Benedict

    2017-03-01

    To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) for HPV associated oropharyngeal carcinoma (HPV+OPC) is a better discriminator of overall survival (OS), compared with the 7th edition (7th Ed) AJCC/UICC TNM staging following curative radiotherapy (RT). The 5-year OS for all patients with non-metastatic (M0) p16-confirmed OPC treated between 2005 and 2015 was determined and grouped based on the 7th Ed AJCC/UICC TNM and ICON-S staging. A total of 279 patients met the inclusion criteria. The 5-year OS with the 7th Ed TNM classification were Stage I/II 88.9% (95% CI; 70.6-100%), Stage III 93.8% (95% CI; 85.9-100%), Stage IVa 86.4% (95% CI; 81.6-91.5%) and Stage IVb 62.3% (95% CI; 46.8-82.8%). On multivariate Cox regression analysis there was no statistically significant OS difference when comparing Stage I/II with, Stage III (p=0.98, HR=0.97, 95% CI; 0.11-8.64), IVa (p=0.67, HR=1.56, 95% CI; 0.2-11.94) and IVb (p=0.11, HR=5.54, 95% CI; 0.69-44.52), respectively. The 5-year OS with ICON-S staging were Stage I 93.6% (95% CI; 89.4-98.0%), Stage II 81.9% (95% CI; 73.7-91.1%) and Stage III 69.1% (95%; 57.9-82.6%). There was a consistent decrease of OS with increasing stage. On multivariate Cox regression analysis, when compared to Stage I, OS was significantly lower for stage II (p=0.007, HR=2.84, 95% CI; 1.33-6.05) and stage III (p<0.001, HR=3.78, 95% CI; 1.81-7.92), respectively. The ICON-S staging provides better OS stratification for HPV+OPC following RT compared with the 7th Ed TNM staging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Has PET/CT a role in the characterization of indeterminate lung lesions on staging CT in colorectal cancer? A prospective study

    DEFF Research Database (Denmark)

    Jess, P.; Seiersen, M.; Ovesen, H.

    2014-01-01

    Purpose CT has been found superior to chest x-ray to detect lung malignances. However, indeterminate lung lesions (ILL) are found in 4-42% by using CT in staging colorectal cancer (CRC) patients. Our aim was to examine the frequency of ILL on staging CT and the rate of the ILL being malignant.......12). Conclusions Even though a relative low number of ILL turn out to be malignant it seems advisable to use PET/CT scan in the follow-up to detect lung metastases as early as possible to better the prognosis. For the same reason all CRC patients should have chest CT included in their follow-up 6-12 months...

  14. 5-Fluorouracil combined with the [6S]-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma. A phase I-II study of two consecutive regimens.

    Science.gov (United States)

    Machover, D; Grison, X; Goldschmidt, E; Zittoun, J; Metzger, G; Richaud, J; Lotz, J P; André, T; Hannoun, L; Marquet, J

    1993-01-01

    Potentiation of the antitumor activity of 5-fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase (TS), fluorodeoxyuridylate (FdUMP), and methylene tetrahydrofolate (5,10-CH2-FH4), which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C6 carbon of the pteridine ring. Only the levorotatory [6S]-folinic acid is transformed into active folate cofactors. However, the [6R]-stereoisomer is not inert; it was shown to interfere with the [6S] form at the cellular level. The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out 2 consecutive phase I-II studies of 5-FU combined with the [6S]-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. Treatment comprised 5-FU by i.v. infusion for 2 hours (the initial dose was 350 mg/m2/d; it was incremented by 25 mg/m2/d until a maximal dose of 550 mg/m2/d) and [6S]-folinic acid (100 mg/m2/d by rapid i.v. injection in Regimen 1, and 100 mg/m2 by rapid i.v. injection followed by a 2-hour infusion of 250 mg/m2 in Regimen 2) for 5 days, every 21 days. Twenty-five pts and 27 pts were assessed in Regimen 1 and in Regimen 2, respectively. They had had no prior chemotherapy. The median follow-up time was 9 months and 15.5 months for patients treated with Regimen 1 and Regimen 2, respectively. For pts treated with Regimen 1, the response rate was 52% (CR, 12%; PR, 40%). The median time to disease progression was 9.2 months. The probability of survival at 12 months was 73%. For pts treated with Regimen 2, the response rate was 37% (CR, 7%; PR, 30%). The median time to disease progression was 8.9 months. The probability of survival at 12 months was 67%. Improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects (WHO grades > or = 3) were diarrhea, dermatitis, and mucositis. One single episode of grade 4 diarrhea occurred. After injection according to the schema in Regimen 1, [6S]-folinic acid was rapidly cleared from plasma (mean t 1/2 alpha and t 1/2 beta of 7.2 and 126 minutes, respectively). The mean concentration of the [6S]-stereoisomer two hours after injection was 5.8 mmol/L. After a rapid i.v. injection of 100 mg/m2 followed by a 2-hour infusion of 250 mg/m2, the mean concentration of [6S]-folinic acid two hours after the injection was 57.5 mmol/L. Pharmacokinetic data suggests saturation of the metabolic conversion of [6S]-folinic acid when large doses are administered. The [6S]-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. However, increase of the daily dose of the folate did not result in a therapeutic improvement. The present results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines.

  15. Clinical impact of FDG-PET/CT on colorectal cancer staging and treatment strategy

    DEFF Research Database (Denmark)

    Petersen, Rasmus K; Hess, Søren; Alavi, Abass

    2014-01-01

    and patients divided as follows: (A) Patients with a change in therapy following FDG-PET/CT and (B) Patients without a change following FDG-PET/CT. Sixty-two patients had colon and five had rectal cancer. Of these, 20 (30%; CI 20.2-41.7) belonged to group A, whereas 47 (70%; CI 58.3-79.8) fell in group B......FDG-PET/CT is rarely used for initial staging of patients with colorectal cancer (CRC). Surgical resection of primary tumor and isolated metastases may result in long-term survival or presumed cure, whereas disseminated disease contraindicates operation. We analyzed a retrospective material...

  16. Sidedness and TP53 mutations impact OS in anti-EGFR but not anti-VEGF treated mCRC - an analysis of the KRAS registry of the AGMT (Arbeitsgemeinschaft Medikamentöse Tumortherapie).

    Science.gov (United States)

    Huemer, Florian; Thaler, Josef; Piringer, Gudrun; Hackl, Hubert; Pleyer, Lisa; Hufnagl, Clemens; Weiss, Lukas; Greil, Richard

    2018-01-03

    In metastatic colorectal cancer (mCRC), the localization of the primary tumour has been shown to be of prognostic as well as predictive relevance. With the aim to investigate clinical and molecular disease characteristics with respect to sidedness in a real-world cohort, we analyzed 161 mCRC patients included in the KRAS Registry of the Arbeitsgemeinschaft Medikamentöse Tumortherapie (AGMT) between January 2006 and October 2013. Right-sided mCRC displayed a worse median overall survival (OS) in comparison to left-sided disease (18.1 months [95%-CI: 14.3-40.7] versus 32.3 months [95%-CI: 25.5-38.6]; HR: 1.63 [95%-CI: 1.13-2.84]; p = 0.013). The choice of the biological agent in front-line therapy had a statistically significant impact on median OS in patients with right-sided tumours (anti-epidermal growth factor receptor (EGFR): 10.6 months [95%-CI: 5.2-NA]; anti-vascular endothelial growth factor (VEGF): 26.2 months [95%-CI: 17.9-NA]; HR: 2.69 [95%-CI: 1.30-12.28]; p = 0.015) but not in patients with left-sided tumours (anti-EGFR: 37.0 months [95%-CI: 20.2-56.6]; anti-VEGF: 32.3 months [95%-CI: 23.6-41.1]; HR: 0.97 [95%-CI: 0.56-1.66]; p = 0.905). When evaluating molecular characteristics of tumour samples, we found a clinically meaningful trend towards an inferior OS in TP53 mutant mCRC treated with anti-EGFR based therapy compared to anti-VEGF based therapy (17.1 months [95%-CI: 8.7-NA] versus 38.3 months [95%-CI: 23.6-48.0], HR = 1.95 [95%-CI: 0.95-5.88]; p = 0.066), which was not significantly dependent on sidedness. This was not the case in patients with TP53 wild-type tumours. Therefore we evaluated the combined impact of sidedness and TP53 mutation status in the anti-EGFR treated cohort and patients with left-sided/TP53 wild-type mCRC showed the longest median OS (38.9 months) of all groups (right-sided/TP53 mutant: 12.1 months; right-sided/TP53 wild-type: 8.9 months; left-sided/TP53 mutant: 18.4 months; p = 0.020). TP53

  17. Between Stage and Screen

    NARCIS (Netherlands)

    Tornqvist, Egil

    1996-01-01

    Ingmar Bergman is worldwide known as a film and stage director. Yet no-one has attempted to compare his stage and screen activities. In Between stage and screen Egil Tornqvist examines formal and thematical correspondences and differences between a number of Bergman's stage, screen, and radio

  18. A modified TNM staging system for non-metastatic colorectal cancer based on nomogram analysis of SEER database.

    Science.gov (United States)

    Kong, Xiangxing; Li, Jun; Cai, Yibo; Tian, Yu; Chi, Shengqiang; Tong, Danyang; Hu, Yeting; Yang, Qi; Li, Jingsong; Poston, Graeme; Yuan, Ying; Ding, Kefeng

    2018-01-08

    To revise the American Joint Committee on Cancer TNM staging system for colorectal cancer (CRC) based on a nomogram analysis of Surveillance, Epidemiology, and End Results (SEER) database, and to prove the rationality of enhancing T stage's weighting in our previously proposed T-plus staging system. Total 115,377 non-metastatic CRC patients from SEER were randomly grouped as training and testing set by ratio 1:1. The Nomo-staging system was established via three nomograms based on 1-year, 2-year and 3-year disease specific survival (DSS) Logistic regression analysis of the training set. The predictive value of Nomo-staging system for the testing set was evaluated by concordance index (c-index), likelihood ratio (L.R.) and Akaike information criteria (AIC) for 1-year, 2-year, 3-year overall survival (OS) and DSS. Kaplan-Meier survival curve was used to valuate discrimination and gradient monotonicity. And an external validation was performed on database from the Second Affiliated Hospital of Zhejiang University (SAHZU). Patients with T1-2 N1 and T1N2a were classified into stage II while T4 N0 patients were classified into stage III in Nomo-staging system. Kaplan-Meier survival curves of OS and DSS in testing set showed Nomo-staging system performed better in discrimination and gradient monotonicity, and the external validation in SAHZU database also showed distinctly better discrimination. The Nomo-staging system showed higher value in L.R. and c-index, and lower value in AIC when predicting OS and DSS in testing set. The Nomo-staging system showed better performance in prognosis prediction and the weight of lymph nodes status in prognosis prediction should be cautiously reconsidered.

  19. Regional nodal relapse in surgically staged Merkel cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoeller, Ulrike; Mueller, Thomas; Schubert, Tina; Budach, Volker; Ghadjar, Pirus [Charite Universitaetsmedizin Berlin, Department of Radiation Oncology, Berlin (Germany); Brenner, Winfried [Charite Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Kiecker, Felix [Charite Universitaetsmedizin Berlin, Department of Dermatology, Berlin (Germany); Schicke, Bernd [Tumor Center Berlin, Berlin (Germany); Haase, Oliver [Charite Universitaetsmedizin Berlin, Department of Surgery, Berlin (Germany)

    2014-10-08

    The nodal relapse pattern of surgically staged Merkel cell carcinoma (MCC) with/without elective nodal radiotherapy (RT) was studied in a single institution. A total of 51 patients with MCC, 33 % UICC stage I, 14 % II, 53 % III (4 lymph node metastases of unknown primary) were eligible. All patients had surgical staging: 23 patients sentinel node biopsy (SNB), 22 patients SNB followed by lymphadenectomy (LAD) and 6 patients LAD. In all, 94 % of the primary tumors (PT) were completely resected; 57 % of patients received RT, 51 % of known PT sites, 33 % (8/24 patients) regional RT to snN0 nodes and 68 % (17/27 patients) to pN+ nodes, mean reference dose 51.5 and 50 Gy, respectively. Mean follow-up was 6 years (range 2-14 years). A total of 22 % (11/51) patients developed regional relapses (RR); the 5-year RR rate was 27 %. In snN0 sites (stage I/II), relapse occurred in 5 of 14 nonirradiated vs. none of 8 irradiated sites (p = 0.054), resulting in a 5-year RR rate of 33 % versus 0 % (p = 0.16). The crude RR rate was lower in stage I (12 %, 2/17 patients) than for stage II (43 %, 3/7 patients). In stage III (pN+), RR appeared to be less frequent in irradiated sites (18 %, 3/14 patients) compared with nonirradiated sites (33 %, 3/10 patients, p = 0.45) with 5-year RR rates of 23 % vs. 34 %, respectively. Our data suggest that adjuvant nodal RT plays a major role even if the sentinel nodes were negative. Adjuvant RT of the lymph nodes in patients with stage IIa tumors and RT after LAD in stage III tumors is proposed and should be evaluated prospectively. (orig.) [German] Untersucht wurde das regionaere Rezidivmuster des Merkelzell-Karzinoms (MCC) nach chirurgischem Staging und stadienadaptierter Therapie. Eingeschlossen wurden 51 Patienten mit lokalisiertem MCC: 33 % hatten UICC-Stadium-I-, 14 % -II-, 53 % -III-Tumoren (davon 4 Lymphknotenmetastasen eines unbekannten Primaertumors). Alle Patienten erhielten ein chirurgisches Staging: 23 Waechterlymphknotenbiopsien (SNB

  20. ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study

    Directory of Open Access Journals (Sweden)

    Lee Su-Chen

    2008-02-01

    Full Text Available Abstract Background Early relapse in colorectal cancer (CRC patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes. Methods Six gene polymorphisms functional in drug-metabolism – GSTP1 Ile105Val, ABCB1 Ile1145Ile, MTHFR Ala222Val, TYMS double (2R or triple (3R tandem repeat – and DNA-repair genes – ERCC2 Lys751Gln and XRCC1 Arg399Gln – were assessed in 201 CRC patients using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP technique and DNA sequencing. Patients were diagnosed as either high-risk stage II (T2 and 3 N0 M0 or III (any T N1 and 2 M0 and were administered adjuvant chemotherapy regimens that included 5-fluorouracil (5FU and leucovorin (LV. The correlations between genetic polymorphisms and patient clinicopathological features and relapses were investigated. Results In this study, the distributions of GSTP1 (P = 0.003, ABCB1 (P = 0.001, TYMS (P ERCC2 (P XRCC1 (P = 0.006 genotypes in the Asian population, with the exception of MTHFR (P = 0.081, differed significantly from their distributions in a Caucasian population. However, the unfavorable genotype ERCC2 2251A>C (P = 0.006, tumor invasion depth (P = 0.025, lymph node metastasis (P = 0

  1. Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer

    International Nuclear Information System (INIS)

    Takahashi, Hidenori; Ishikawa, Toshiaki; Ishiguro, Megumi; Okazaki, Satoshi; Mogushi, Kaoru; Kobayashi, Hirotoshi; Iida, Satoru; Mizushima, Hiroshi; Tanaka, Hiroshi; Uetake, Hiroyuki; Sugihara, Kenichi

    2015-01-01

    The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified seventeen candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients. The online version of this article (doi:10.1186/s12885-015-1783-y) contains supplementary material, which is available to authorized users

  2. The management of patients with limited-stage classical Hodgkin lymphoma.

    Science.gov (United States)

    Gospodarowicz, Mary K; Meyer, Ralph M

    2006-01-01

    The term limited-stage Hodgkin lymphoma refers to those patients with stage I-II disease and an absence of bulky disease. Among those patients with classical Hodgkin lymphoma, approximately one-third of patients will fall into this category. As long-term disease control can now be anticipated in more than 90% of these patients, management strategies must increasingly address the need to reduce the long-term treatment-related risks. Current treatment options include use of combined modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation or treatment with chemotherapy, currently consisting of ABVD, as a single modality. The choice of treatment between these two options involves specific trade-offs that must balance issues of disease control against long-term risk of late effects.

  3. Feasibility of thoracoscopic thymectomy for treatment of early-stage thymoma.

    Science.gov (United States)

    Odaka, Makoto; Shibasaki, Takamasa; Asano, Hisatoshi; Marushima, Hideki; Yamashita, Makoto; Morikawa, Toshiaki

    2015-11-01

    The objective of this study was to evaluate the feasibility of thoracoscopic thymectomy (TT) for treatment of early-stage thymoma and to compare the outcomes with those after open thymectomy (OT). A retrospective review of 98 patients who underwent TT or OT of Masaoka stage I-II thymoma without thymic cancer between 1996 and 2013 was performed. Thoracoscopic thymectomy was performed in 67 patients, and OT was performed in 31 patients. The intraoperative blood loss amounts differed significantly between the TT group and OT group (100 vs 185 mL, P = 0.0070). The postoperative hospital stay was significantly shorter in the TT group than in the OT group (4 vs 12 days, P thymoma. © 2015 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

  4. Colorectal cancers detected through screening are associated with lower stages and improved survival

    DEFF Research Database (Denmark)

    Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus Hedebo

    2014-01-01

    in the feasibility study cohort were reviewed with respect to the effect of screening participation on stages and survival. MATERIAL AND METHODS: All cases of CRC in a feasibility study cohort diagnosed from the beginning of the study until two years after the study ended were identified. Differences...... in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through χ(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time. RESULTS: Colon cancers...... detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior...

  5. Gender, anthropometric factors and risk of colorectal cancer with particular reference to tumour location and TNM stage: a cohort study

    Directory of Open Access Journals (Sweden)

    Brändstedt Jenny

    2012-10-01

    Full Text Available Abstract Background It remains unclear whether the increased risk of colorectal cancer (CRC associated with obesity differs by gender, distribution of fat, tumour location and clinical (TNM stage. The primary aim of this study was to examine these associations in 584 incident colorectal cancer cases from a Swedish prospective population-based cohort including 28098 men and women. Methods Seven anthropometric factors; height, weight, bodyfat percentage, hip circumference, waist circumference, BMI and waist-hip ratio (WHR were categorized into quartiles of baseline anthropometric measurements. Relative risks of CRC, total risk as well as risk of different TNM stages, and risk of tumours located to the colon or rectum, were calculated for all cases, women and men, respectively, using multivariate Cox regression models. Results Obesity, as defined by all anthropometric variables, was significantly associated with an overall increased risk of CRC in both women and men. While none of the anthropometric measures was significantly associated with risk of tumour (T-stage 1 and 2 tumours, all anthropometric variables were significantly associated with an increased risk of T-stage 3 and 4, in particular in men. In men, increasing quartiles of weight, hip, waist, BMI and WHR were significantly associated with an increased risk of lymph node positive (N1 and N2 disease, and risk of both non-metastatic (M0 and metastatic (M1 disease. In women, there were no or weak associations between obesity and risk of node-positive disease, but statistically significant associations between increased weight, bodyfat percentage, hip, BMI and M0 disease. Interestingly, there was an increased risk of colon but not rectal cancer in men, and rectal but not colon cancer in women, by increased measures of weight, hip-, waist circumference and bodyfat percentage. Conclusions This study is the first to show a relationship between obesity, measured as several different

  6. Geographic and Demographic Disparities in Late-stage Breast and Colorectal Cancer Diagnoses Across the US

    Directory of Open Access Journals (Sweden)

    Lee R Mobley

    2015-08-01

    Full Text Available Problem: In 2009, breast cancer was the most common cancer in women, and colorectal cancer was the third most common cancer in both men and women. Currently, the majority of colorectal and almost 1/3 of breast cancers are diagnosed at an advanced stage in the US, which results in higher morbidity and mortality than would obtain with earlier detection. The incidence of late-stage cancer diagnoses varies considerably across the US, and few analyses have examined the entire US.Purpose: Using the newly available US Cancer Statistics database representing 98% of the US population, we perform multilevel analysis of the incidence of late-stage cancer diagnoses and translate the findings via bivariate mapping, answering questions related to both Why and Where demographic and geographic disparities in these diagnoses are observed.Methods: To answer questions related to Why disparities are observed, we utilize a three-level, random-intercepts model including person-, local area-, and region- specific levels of influence. To answer questions related to Where disparities are observed, we generate county level robust predictions of late-stage cancer diagnosis rates and map them, contrasting counties ranked in the upper and lower quantiles of all county predicted rates. Bivariate maps are used to spatially translate the geographic variation among US counties in the distribution of both BC and CRC late-stage diagnoses.Conclusions: Empirical modeling results show demographic disparities, while the spatial translation of empirical results shows geographic disparities that may be quite useful for state cancer control planning. Late stage BC and CRC diagnosis rates are not spatially random, manifesting as place-specific patterns that compare counties in individual states to counties across all states. Providing a relative comparison that enables assessment of how results in one state compare with others, this paper is to be disseminated to all state cancer control

  7. Prognostic Value of E-cadherin-, CD44-, and MSH2-associated Nomograms in Patients With Stage II and III Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jinmiao Qu

    2017-04-01

    Full Text Available BACKGROUND: To evaluate the prognostic value of E-cadherin, CD44, and MSH2 expression for colorectal cancer (CRC and construct nomograms that can predict prognosis. METHODS: We retrospectively analyzed the expression of E-cadherin, CD44, and MSH2 in 223 paraffin-embedded stage II and III CRC specimens using immunohistochemistry in the training cohort. Their prognostic values were assessed using Kaplan–Meier curves and univariate and multivariate COX regression models. Moreover, a number of risk factors were used to form nomograms to evaluate survival, and Harrell's concordance index (C-index was used to evaluate the predictive accuracy. Further validation of the nomograms was performed in an independent cohort of 115 cases. RESULTS: Low E-cadherin expression and low CD44 expression were significantly associated with diminished overall survival (OS and disease-free survival (DFS in stage II and III CRC patients and patients with negative MSH2 expression had better clinical outcomes. Moreover, the multivariate COX analysis identified E-cadherin, CD44 and MSH2 expression as independent prognostic factors for DFS and OS. Using these three markers and three clinicopathological risk variables, two nomograms were constructed and externally validated for predicting OS and DFS (C-index: training cohort, 0.779 (95% CI 0.722–0.835 and 0.771 (0.720–0.822, respectively; validation cohort, 0.773 (0.709–0.837 and 0.670 (0.594–0.747, respectively. CONCLUSION: The expression levels of E-cadherin, CD44 and MSH2 were independent prognostic factors for stage II and III CRC patients. By incorporating clinicopathological features and these biomarkers, we have established two nomograms that could be used to make individualized predictions for OS and DFS.

  8. Breast cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  9. Seven Stages of Alzheimer's

    Science.gov (United States)

    ... Dementias . Learn more: Daily Care and Behaviors Severe Alzheimer's disease (late-stage) Get support Late-stage care decisions can be some of the hardest families face. Connect with other caregivers who have been through the process on our ...

  10. Stages of Adolescence

    Science.gov (United States)

    ... Español Text Size Email Print Share Stages of Adolescence Page Content Article Body Adolescence, these years from puberty to adulthood, may be roughly divided into three stages: early adolescence, generally ages eleven to fourteen; middle adolescence, ages ...

  11. Beyond Erikson's Eight Stages.

    Science.gov (United States)

    Whitney, Ruth

    1979-01-01

    Erik Erikson has described eight stages of the healthy personality. This essay offers a revised version of the eight stages. Although most individuals develop through the eight stages, each is personally unique because patterns of fluctuation between safety and growth differ from one individual to another. (Author)

  12. Cervical Cancer Stage IIIA

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IIIA Add to My Pictures View /Download : ... 1275x1275 View Download Large: 2550x2550 View Download Title: Cervical Cancer Stage IIIA Description: Stage IIIA cervical cancer; drawing ...

  13. Cervical Cancer Stage IVA

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IVA Add to My Pictures View /Download : ... 1575x1200 View Download Large: 3150x2400 View Download Title: Cervical Cancer Stage IVA Description: Stage IVA cervical cancer; drawing ...

  14. Cervical Cancer Stage IVB

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IVB Add to My Pictures View /Download : ... 1200x1305 View Download Large: 2400x2610 View Download Title: Cervical Cancer Stage IVB Description: Stage IVB cervical cancer; drawing ...

  15. Cervical Cancer Stage IIIB

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IIIB Add to My Pictures View /Download : ... 1425x1326 View Download Large: 2850x2651 View Download Title: Cervical Cancer Stage IIIB Description: Stage IIIB cervical cancer; drawing ...

  16. Cervical Cancer Stage IB

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IB Add to My Pictures View /Download : ... 1613x1200 View Download Large: 3225x2400 View Download Title: Cervical Cancer Stage IB Description: Stage IB1 and IB2 cervical ...

  17. Cervical Cancer Stage IA

    Science.gov (United States)

    ... historical Searches are case-insensitive Cervical Cancer Stage IA Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Cervical Cancer Stage IA Description: Stage IA1 and IA2 cervical cancer; drawing ...

  18. Combination of adjuvant chemotherapy and radiotherapy is associated with improved survival at early stage type II endometrial cancer and carcinosarcoma.

    Science.gov (United States)

    Sozen, Hamdullah; Çiftçi, Rumeysa; Vatansever, Dogan; Topuz, Samet; Iyibozkurt, Ahmet Cem; Bozbey, Hamza Ugur; Yaşa, Cenk; Çali, Halime; Yavuz, Ekrem; Kucucuk, Seden; Aydiner, Adnan; Salihoglu, Yavuz

    2016-04-01

    The aim of this study was to describe the impact of postoperative adjuvant treatment modalities and identify risk factors associated with recurrence and survival rates in women diagnosed with early stage type II endometrial cancer and carcinosarcoma. In this retrospective study, patients diagnosed with early stage (stages I-II) carcinosarcoma and type II endometrial cancer were reviewed. All women underwent comprehensive surgical staging. Postoperative treatment options of chemotherapy (CT), radiotherapy (RT), observation (OBS) and chemotherapy-radiotherapy (CT-RT) combination were compared in terms of recurrence and survival outcome. In CT-RT treatment arm, recurrence rate was found as 12.5% and this result is significantly lower than the other treatment approaches (P = 0.01 CT alone: 33.3%, RT alone: 26.7%, OBS: 62.5%). Three-year disease free survival(DFS) rate and overall survival (OS) rate were statistically higher for the group of women treated with combination of CT-RT (92-95%) compared to the women treated with RT alone (65-72%), treated with CT alone (67-74%) and women who received no adjuvant therapy (38-45%). The multivariate analysis revealed that carcinosarcoma histology was associated with shortened DFS and OS (P = 0.001, P = 0.002). On the other hand, being at stage Ia (P = 0.01, P = 0.04) and receiving adjuvant treatment of CT-RT combination (P = 0.005, P = 0.002) appeared to lead to increased DFS and OS rates. We identified that a combination treatment of chemotherapy and radiotherapy is superior compared to other postoperative adjuvant treatment approaches concerning PFS, OS and recurrence rates in stages I-II of type II endometrial cancers and uterine carcinosarcoma. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  19. Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma

    International Nuclear Information System (INIS)

    Hamilton, Chad A.; Liou, W.-S.; Osann, Kathryn; Berman, Michael L.; Husain, Amreen; Teng, Nelson N.; Kapp, Daniel S.; Chan, John K.

    2005-01-01

    Purpose: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. Methods and Materials: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. Results: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. Conclusion: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma

  20. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    Science.gov (United States)

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  1. Vaginal brachytherapy for early-stage carcinosarcoma of the uterus.

    Science.gov (United States)

    Brown, Lindsay C; Petersen, Ivy A; Haddock, Michael G; Bakkum-Gamez, Jamie N; Lee, Larissa J; Cimbak, Nicole C; Berkowitz, Ross S; Viswanathan, Akila N

    2015-01-01

    Uterine carcinosarcoma (CS) is an aggressive malignancy and the optimal adjuvant treatment is not well-established. We report outcomes with vaginal brachytherapy (VB) for women with early-stage CS. A multi-institutional retrospective study of Stage I-II CS treated with hysterectomy, surgical staging, and adjuvant high-dose-rate VB without external-beam pelvic radiotherapy was performed. Rates of vaginal control, pelvic control, locoregional control, disease-free survival, and overall survival were determined using the Kaplan-Meier method. 33 patients were identified. Prescribed VB dose was 21 Gy in three fractions (n = 15 [45%]) or 24 Gy in six fractions (n = 18 [55%]). Eighteen patients (55%) received chemotherapy. Median followup was 2.0 years. Twenty-seven patients (82%) underwent pelvic lymphadenectomy, 5 (15%) had nodal sampling, and 1 (3%) had no lymph node assessment. Relapse occurred in 11 patients (33%), all of whom had lymph node evaluation. Locoregional relapse was a component of failure in 6 patients (18%), of whom 3 (9%) failed in the pelvis alone. Three patients (9%) had simultaneous distant and locoregional relapse (two vaginal, one pelvic). Five additional patients (15%) had distant relapse. Six of the 11 patients (55%) with disease recurrence received chemotherapy. Two-year vaginal control and pelvic control were 94% and 87%. Two-year locoregional control, disease-free survival, and overall survival were 81%, 66%, and 79%. Despite having early-stage disease and treatment with VB, patients in this series had relatively high rates of local and distant relapse. Patients who undergo lymphadenectomy and VB remain at risk for relapse. Novel treatment strategies are needed. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  2. Hepatosplenic volumetric assessment at MDCT for staging liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Pickhardt, Perry J.; Malecki, Kyle; Hunt, Oliver F.; Beaumont, Claire; Kloke, John; Ziemlewicz, Timothy J.; Lubner, Meghan G. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

    2017-07-15

    To investigate hepatosplenic volumetry at MDCT for non-invasive prediction of hepatic fibrosis. Hepatosplenic volume analysis in 624 patients (mean age, 48.8 years; 311 M/313 F) at MDCT was performed using dedicated software and compared against pathological fibrosis stage (F0 = 374; F1 = 48; F2 = 40; F3 = 65; F4 = 97). The liver segmental volume ratio (LSVR) was defined by Couinaud segments I-III over segments IV-VIII. All pre-cirrhotic fibrosis stages (METAVIR F1-F3) were based on liver biopsy within 1 year of MDCT. LSVR and total splenic volumes increased with stage of fibrosis, with mean(±SD) values of: F0: 0.26 ± 0.06 and 215.1 ± 88.5 mm{sup 3}; F1: 0.25 ± 0.08 and 294.8 ± 153.4 mm{sup 3}; F2: 0.331 ± 0.12 and 291.6 ± 197.1 mm{sup 3}; F3: 0.39 ± 0.15 and 509.6 ± 402.6 mm{sup 3}; F4: 0.56 ± 0.30 and 790.7 ± 450.3 mm{sup 3}, respectively. Total hepatic volumes showed poor discrimination (F0: 1674 ± 320 mm{sup 3}; F4: 1631 ± 691 mm{sup 3}). For discriminating advanced fibrosis (≥F3), the ROC AUC values for LSVR, total liver volume, splenic volume and LSVR/spleen combined were 0.863, 0.506, 0.890 and 0.947, respectively. Relative changes in segmental liver volumes and total splenic volume allow for non-invasive staging of hepatic fibrosis, whereas total liver volume is a poor predictor. Unlike liver biopsy or elastography, these CT volumetric biomarkers can be obtained retrospectively on routine scans obtained for other indications. (orig.)

  3. Esophageal dysfunction in different stages of Parkinson's disease.

    Science.gov (United States)

    Suttrup, I; Suttrup, J; Suntrup-Krueger, S; Siemer, M-L; Bauer, J; Hamacher, C; Oelenberg, S; Domagk, D; Dziewas, R; Warnecke, T

    2017-01-01

    Dysphagia is a clinically relevant symptom in patients with Parkinson's disease (PD) leading to pronounced reduction in quality of life and other severe complications. Parkinson's disease-related dysphagia may affect the oral and pharyngeal, as well as the esophageal phase of swallowing. To examine the nature and extend of esophageal dysphagia in different stages of PD and their relation to oropharyngeal dysfunction, we examined 65 PD patients (mean age 66.3±9.7 years, mean disease duration 7.9±5.8 years, mean Hoehn & Yahr [H&Y] stage 2.89±0.91) and divided into three groups (early [H&Y I+II; n=21], intermediate [H&Y III; n=25], and advanced stadium [H&Y IV+V; n=19]), using esophageal high-resolution manometry (HRM) to detect esophageal motor disorders. Oropharyngeal impairment was assessed using fiberoptic endoscopic evaluation of swallowing. Major esophageal motor disorders were detected in nearly one third of the PD patients. Minor impairment of the esophageal body was present in 95% of participants and throughout all disease stages with pathological findings especially in peristalsis and intrabolus pressure (IBP). The IBP was found to significantly increase in the advanced stadium. Although dysfunction of the upper and lower esophageal sphincters was observed in individual patients, alterations in these esophageal segments revealed no statistical significance compared with normative data. No clear association was found between the occurrence of oropharyngeal dysphagia and esophageal impairment. Esophageal body impairment in PD is a frequent phenomenon during all disease stages, which possibly reflects α-synucleinopathy in the enteric nervous system. © 2016 John Wiley & Sons Ltd.

  4. Fluxos informacionais para o monitoramento da Convenção dos Direitos da Criança: a atuação da rede NGO Group for CRCInformation follow and the monitoring process of the convention on the rights of child by NGO Group for CRC network

    Directory of Open Access Journals (Sweden)

    Maria Guiomar da Cunha Frota

    2010-05-01

    Full Text Available O presente artigo apresenta os resultados de uma pesquisa que investiga uma rede social internacional denominada NGO Group for CRC. A rede é composta por cerca de noventa organizações não governamentais e foi criada para monitorar a implementação da Convenção dos Direitos da Criança (CRC. A CRC é o principal documento jurídico relativo aos direitos da criança, tendo sido aprovada pela totalidade dos países pertencentes à ONU, com exceção dos EUA. Pretende-se especificamente analisar o fluxo informacional que se estabelece em meio à rede, seus membros e as organizações que a ela se associam. As questões investigadas são as seguintes: 1 Em que medida o fluxo informacional torna-se parte intrínseca da estrutura em rede? 2 Como os fluxos informacionais se configuram e de que modo são apropriados e veiculados pela rede NGO Group for CRC no curso do monitoramento da implementação da Convenção dos Direitos da Criança?This paper presents the research results about the social network NGO Group for CRC which is an articulation of non governmental organizations related to children's rights. This paper analyzes the information flow inside the network, among its members and among the network organizations. The Convention on the Rights of the Child (CRC was approved in 1989 by the General Assembly of the United Nations, being ratified in its totality by the countries members, with the exception of the United States of America. The investigated questions are: 1 How is the role of the information flow in the network structure? 2 How is the information flow configured to support the implementation monitoring process of the Convention on the Rights of the Child?

  5. Multiple stage railgun

    International Nuclear Information System (INIS)

    Aaland, K.; Hawke, R.S.; Scudder, J.K.

    1982-01-01

    A multiple stage magnetic railgun accelerator for accelerating a projectile by movement of a plasma arc along the rails. The railgun is divided into a plurality of successive rail stages which are sequentially energized by separate energy sources as the projectile moves through the bore of the railgun. Propagation of energy from an energized rail stage back towards the breech end of the railgun can be prevented by connection of the energy sources to the rails through isolation diodes. Propagation of energy from an energized rail stage back towards the breech end of the railgun can also be prevented by dividing the rails into electrically isolated rail sections. In such case means are used to extinguish the arc at the end of each energized stage and a fuse or laser device is used to initiate a new plasma arc in the next energized rail stage

  6. Efecto de la presión de C2H2 sobre las propiedades tribológicas y mecánicas de recubrimientos de CrC depositados por evaporación por arco catódico (EAC)

    OpenAIRE

    Maryory Astrid Gómez Botero; Arturo Lousa; Joan Esteve Pujo

    2010-01-01

    Se obtuvieron recubrimientos monocapa de CrC por evaporación por arco catódico (EAC). Se investigaron las propiedades tribológicas de los recubrimientos mediante pruebas de deslizamiento en seco usando un tribómetro de bola sobre disco. Las propiedades mecánicas se estudiaron por nanoindentación dinámica. Los valores de los coeficientes de fricción de los recubrimientos monocapa de CrC mostraron buena correlación con el contenido de carbono de estos recubrimientos, presentando el más bajo coe...

  7. Turbine stage model

    International Nuclear Information System (INIS)

    Kazantsev, A.A.

    2009-01-01

    A model of turbine stage for calculations of NPP turbine department dynamics in real time was developed. The simulation results were compared with manufacturer calculations for NPP low-speed and fast turbines. The comparison results have shown that the model is valid for real time simulation of all modes of turbines operation. The model allows calculating turbine stage parameters with 1% accuracy. It was shown that the developed turbine stage model meets the accuracy requirements if the data of turbine blades setting angles for all turbine stages are available [ru

  8. Colorectal cancers detected through screening are associated with lower stages and improved survival

    DEFF Research Database (Denmark)

    Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus Hedebo

    2014-01-01

    INTRODUCTION: Population screening for colorectal cancer (CRC) using faecal occult blood test (FOBT) will be introduced in Denmark in 2014. Prior to the implementation of the screening programme, a feasibility study was performed in 2005-2006. In this paper, occurrences of colorectal cancer...... in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through χ(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time. RESULTS: Colon cancers...... detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior...

  9. Serum biomarker profiles of interleukin-6, tumor necrosis factor alpha, matrix-metalloproteinase-2, and vascular endothelial growth factor in endometriosis staging

    Directory of Open Access Journals (Sweden)

    Wachyu Hadisaputra

    2013-05-01

    Full Text Available Background: The focus of this study was to compare serum biomarkers: interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, matrix-metalloproteinase-2 (MMP-2 and vascular endothelial growth factor (VEGF in endometriosis stage I-II and stage III-IV. Methods: This is a cross-sectional study. Forty endometriosis patients were diagnosed using laparoscopy procedure. Serum sample was taken before the surgery. The serum biomarkers (IL-6, TNF-α, MMP-2, and VEGF were analyzed with ELISA method at the end of research. Mean of serum biomarkers in endometrosis stage I-II and stage III-IV were compared using unpaired t-test. Variables that show significant mean difference were tested using ROC measurement and the optimal cut-off point was determined. Results: There was no significant difference in mean serum biomarkers level of IL-6, TNF-α, and MMP-2 between endometriosis stage I-II and stage III-IV (1.58 ± 0.78 vs 1.55 ± 0.98 pg/mL, 1.5 ± 0.47 vs 1.49 ± 0.29 pg/mL, and 152.04 ± 27.32 vs 140.98 ± 28.08 ng/mL, respectively. On the other hand, the comparison of VEGF level in endometriosis stage I-II and stage III-IV demonstrated significant difference (289.76 ± 188.13 vs 581.29 ± 512.85 pg/mL (p < 0.05. Mean difference of VEGF had AUC of 74.5%. Optimal cut-off point for VEGF was ≥ 314.75 pg/mL with sensitivity 78.6% and specificity 69.2%. Conclusion: This study showed that serum biomarkers of VEGF level (but not IL-6, TNF-α, and MMP-2 can be used to measure the degree of severity in endometriosis. VEGF level of 314.75 pg/mL represents the cut-off point between lower and higher stage of severity. (Med J Indones. 2013;22:76-82Keywords: Endometriosis, interleukin-6, matrix-metalloproteinase-2, TNF-α, vascular endhothelial growth factor

  10. [Increased oxidized LDL cholesterol levels in peritoneal fluid of women with advanced-stage endometriosis].

    Science.gov (United States)

    Polak, Grzegorz; Mazurek, Diana; Rogala, Ewelina; Nowicka, Aldona; Derewianka-Polak, Magdalena; Kotarski, Jan

    2011-03-01

    Proinflammatory and prooxidative environment in the peritoneal cavity may be involved in the pathogenesis of endometriosis. Imbalance between reactive oxygen species levels and the antioxidant capacity leads to oxidation of low-density lipoproteins (LDL). The importance of oxidized LDL (Ox-LDL) in the development of atherosclerosis is well recognized. The aim of our study was to evaluate for the presence of ox-LDL in the peritoneal fluid (PF) of women with and without endometriosis. A total of 60 women who underwent laparoscopy were divided into groups: endometriosis sufferers with minimal to mild (n 20) and moderate to severe (n 20) stages, and the reference group (n 20) with functional follicle ovarian cysts. Oxidized LDL levels were determined in the PF using enzyme immunoassay Oxidized LDL levels were detectable in all peritoneal fluid samples. Significantly increased levels of ox-LDL were observed in PF of women with stage III/IV endometriosis compared to the reference group (p = 0.03). However peritoneal fluid ox-LDL concentrations did not differ significantly between patients with minimal/mild and women with moderate/severe stage of the disease (p = 0.2). No significant difference in the PF ox-LDL concentrations was also found between women with stage I/II endometriosis and patients with follicle cysts (p = 0.3). Increased peritoneal fluid ox-LDL levels observed in women with advanced-stage endometriosis suggest the important role of oxidative stress in the pathogenesis of the disease.

  11. Freqüência das infecções pelo HIV-1, rubéola, sífilis, toxoplasmose, citomegalovírus, herpes simples, hepatite B, hepatite C, doença de Chagas e HTLV I/II em gestantes, do Estado de Mato Grosso do Sul Frequency of HIV-1, rubella, syphilis, toxoplasmosis, cytomegalovirus, simple herpes virus, hepatitis B, hepatitis C, Chagas’ disease and HTLV I/II infection in pregnant women of State of Mato Grosso do Sul

    Directory of Open Access Journals (Sweden)

    Ernesto Antonio Figueiró-Filho

    2007-04-01

    Full Text Available Objetivou-se avaliar a freqüência das infecções por sífilis, rubéola, hepatite B, hepatite C, toxoplasmose, doença de Chagas, HTLV I/II, herpes simples, HIV-1 e citomegalovírus em gestantes e relacionar a faixa etária das pacientes com a freqüência das infecções. Estudo transversal de 32.512 gestantes submetidas à triagem pré-natal no período de novembro de 2002 a outubro de 2003. As freqüências encontradas foram de 0,2% para infecção pelo vírus HIV-1, 0,03% para rubéola, 0,8% para sífilis, 0,4% para toxoplasmose, 0,05% para infecção aguda pelo citomegalovírus, 0,02% pelo vírus herpes simples, 0,3% para hepatite B (HBsAg, 0,1% para hepatite C, 0,1% para HTLV I/II e 0,1% para doença de Chagas. Houve associação significativa entre faixa etária e infecções por rubéola, citomegalovírus, doença de Chagas e herpes vírus. As freqüências de rubéola, sífilis, toxoplasmose, doença de Chagas e citomegalovírus nas gestantes encontram-se abaixo dos valores descritos na literatura.It was aimed to estimate the frequency of syphilis, rubella, hepatitis B, hepatitis C, toxoplasmosis, Chagas’ disease, HTLV I/II, simple herpes virus, HIV-1 and cytomegalovirus in pregnant women and to evaluate the relationship between age and the frequency of the infections studied. A transversal study of 32,512 pregnant women submitted to pre-natal sreening in the period of November 2002 to October 2003. The frequency of the tried infections among the pregnant women were 0.2% of HIV-1, 0.03% of rubella, 0.8% of syphilis, 0.4% of toxoplasmosis, 0.05% of cytomegalovirus, 0.02% of simple herpes virus, 0.3% of HBsAg, 0.1% of hepatitis C, 0.1% of HTLV and 0.1% of Chagas’ disease. There was significative statistical association between age and prenatal infection of rubella, cytomegalovirus, Chagas’ disease and herpes virus. The rates of frequency of rubella, syphilis, toxoplasmosis, Chagas’ disease and cytomegalovirus in pregnant women studied were lower than the compared rates.

  12. Staging of cutaneous melanoma

    NARCIS (Netherlands)

    P. Mohr (P.); A.M.M. Eggermont (Alexander); A. Hauschild (Axel); A. Buzaid (A.)

    2009-01-01

    textabstractThe American Joint Committee on Cancer (AJCC) staging of cutaneous melanoma is a continuously evolving system. The identification of increasingly more accurate prognostic factors has led to major changes in melanoma staging over the years, and the current system described in this review

  13. The association between fatalistic beliefs and late stage at diagnosis of lung and colorectal cancer

    Science.gov (United States)

    Lyratzopoulos, Georgios; Liu, Michael Pang-Hsiang; Abel, Gary A.; Wardle, Jane; Keating, Nancy L.

    2015-01-01

    Background Fatalistic beliefs may be implicated in longer help-seeking intervals, and consequently, greater risk of advanced stage at cancer diagnosis. Methods We examined associations between fatalism and stage at diagnosis in a population-based cohort of 4,319 U.S. patients with newly-diagnosed lung or colorectal cancer participating in the Cancer Care Outcomes and Research Surveillance (CanCORS) study. Fatalistic beliefs were assessed with an established measure. A fatalism score (range 4-16) was created by summing Likert-scale responses to four items. Cancer stage at diagnosis was abstracted from medical records by trained staff. Logistic regression was used to assess the association between fatalism score and advanced stage at diagnosis (IV vs I-III), adjusting for socio-demographic and clinical characteristics. Results Overall, 917 (21%) patients had stage IV cancers (lung: 28%, colorectal: 16%). The mean fatalism score was 10.7 (median=11, inter-quartile range 9-12). In adjusted analyses, a higher fatalism score was associated with greater odds of stage IV diagnosis (odds ratio per unit increase in fatalism=1.05, 95% confidence interval 1.02-1.08, p=0.003). Patients with the highest fatalism score had an adjusted 8.9% higher frequency of stage IV diagnosis compared with patients with the lowest score (25.4% vs. 16.5%). Discussion In this large and socioeconomically, geographically and ethnically diverse population of patients with lung and colorectal cancer, fatalistic beliefs were associated with higher risk of advanced stage at diagnosis. Longitudinal studies are needed to confirm causation. Impact These findings support the value of incorporating information about the curability of early-stage cancers in public education campaigns. PMID:25650183

  14. 1981 CRC Octane Number Requirement Survey.

    Science.gov (United States)

    1982-08-01

    The physical inspections of the 1981 fuels were similar to those of the 1980 fuels, although the 70 percent and 90 percent distillation temperatures...in Appendix C, Table C-IV. There were significant differences between the 1981 and 1980 fuels in terms of API gravity, distillation temperatures, and...0 11 0 1 47 33 Total 80 JI -26- Ln C4qr fl. C"U& Ln qt-l 0%knO w O omw en n Y fin wo 0=0 =oo 00 0=0 00 -000000 0 in444 44414441+1 +1+ 4444 41 444 4 1

  15. CRC Handbook of Medical Physics, vol. 3

    International Nuclear Information System (INIS)

    Waggener, R.G.; Kereiakes, J.G.; Shalek, R.J.

    1984-01-01

    In this work, the care and testing of measurement and diagnostic instruments are described in detail. Difficulties encountered with therapeutic and diagnostic calibrations are explored and solutions are suggested. VOLUME III Physics Teaching for Radiologic Technologists, Physics Teaching for Diagnostic Radiology Residents, Physics Teaching for Nuclear Medicine Residents, Physics Teaching for Radiotherapy Residents, Degree Programs in Medical Physics, Radiobiology Teaching, Non-Degree Medical Physics Training and American Board of Radiology Certifications, Radioactivity and Production of Medical Isotopes, Practical Medical Physics Consulting, Radiologic Terminology, Nuclear Medicine Imaging Techniques, Description of Radiotherapy Procedures, Medical Applications of Ultrasonography and Thermography, Glossary of Medical and Anatomical Terms Used in Medical Physics, Equipment List for Medical Physics and Acquisition Priority. Bibliography of Reference Materials. Index

  16. Phase I/II study of preoperative chemo-radiotherapy (CT-RT) using twice daily radiation as concomitant boost during two cycles of taxol (T), cisplatin (C), 5-FU (F) in esophageal cancer: normal tissue tolerance and early results

    International Nuclear Information System (INIS)

    Choi, Noah; Lynch, Thomas; Mathisen, Douglas; Wain, John; Wright, Cameron; Carey, Robert; Grossbard, Michael; Grillo, Hermes

    1997-01-01

    Purpose/Objective: Even though preoperative CT has failed to show survival benefit over surgery alone, preoperative CT-RT may provide such survival advantage. The goal of this study was to evaluate an intensified radiotherapy (RT) schedule in preoperative concurrent CT-RT for toxicities, resection rate, tumor downstaging, pathologic complete remission (CR) and treatment outcome. Materials and Methods: Eligibility included biopsy proven squamous or adenocarcinoma, T2-4N0-1M0 lesions, performance status ≤ 2 of ECOG scale, creatinine ≤ 2.0 mg/dl, WBC ≥ 2,500/μl, and platelets ≥ 75,000//μl. CT consisted of cisplatin (P) 20 mg/m 2 /day (d) x 5 d, 5-FU (F) 800 mg/m 2 /d continuous infusion x 5 d and Taxol (T) 75-125 mg/m 2 (3 hour infusion) on d1 of each cycle. RT delivered 58.5 Gy/34 fractions (F) /5 weeks (wks) to the gross tumor volume by a combination of 45 Gy/25 F/5 wks to a large target volume (6 cm proximal and distal, and 3 cm radial margins beyond the gross tumor) and a boost dose of 13.5 Gy/9 F (1.5 Gy/F x 5 d with the first cycle [wk 1] and 1.5 Gy/F x 4 d with the second cycle [wk 5] of CT) with an interval of ≥ 5 hours between RT to the gross tumor (am) and large target volume (pm) as a means of concomitant boost. Staging work up included barium swallow, chest and head computed tomography, bone scan, esophagoscopy, and endoscopic ultrasound study (EUS). Results: Between April 1995 and February 1997, 38 patients (pts) with locoregional esophageal cancer have been entered into this study. Patient characteristics were as follows: Age 33-84 (median 63), male: female 30 : 8, adenocarcinoma: squamous cell carcinoma 31 : 7. Tumor stages by EUS included T2N0 11 (29%), T2N1 3 (8%), T3N0 14 (37%), T3N1 8 (21%) and T4N0 2 (5%). Taxol dose was escalated from 75 mg/m 2 (7 pts) to 125 mg/m 2 (5 pts) at which dose limiting toxicities were observed in (3(5)) pts (myocardial infarction, pneumonia, grade 4 neutropenia). The remaining 26 pts have been treated with T

  17. Control judicial de la regulación económica en clave de los actos administrativos proferidos por la Comisión de Regulación de Comunicaciones (CRC

    Directory of Open Access Journals (Sweden)

    Camilo Perdomo Villamil

    2014-12-01

    Full Text Available En el contexto de los procesos de liberalización y los nuevos regímenes económicos a nivel constitucional, la regulación económica se posicionó como una de las principales actividades de intervención estatal sobre la economía. Esta se concibe como un instrumento técnico, neutral e independiente, diseñado para resolver las fallas del mercado y armonizar objetivos económicos y no económicos, generalmente contrapuestos. Por tanto, la cabida del control judicial es muy cuestionada, evidenciándose choques entre la garantía de acceso a la justicia de los particulares y la competencia técnica de los reguladores. Así, se efectúa un análisis material de los actos proferidos por las autoridades de regulación en clave de la extensión del principio de legalidad, y basado en las funciones asignadas a la CRC según la Ley 1341 de 2009, con el propósito de determinar los marcos, límites y alcances del control judicial.

  18. Final results of a phase I/II pilot study of capecitabine with or without vinorelbine after sequential dose-dense epirubicin and paclitaxel in high-risk early breast cancer

    Directory of Open Access Journals (Sweden)

    Müller Volkmar

    2010-08-01

    Full Text Available Abstract Background The integration of the non-cross-resistant chemotherapeutic agents capecitabine and vinorelbine into an intensified dose-dense sequential anthracycline- and taxane-containing regimen in high-risk early breast cancer (EBC could improve efficacy, but this combination was not examined in this context so far. Methods Patients with stage II/IIIA EBC (four or more positive lymph nodes received post-operative intensified dose-dense sequential epirubicin (150 mg/m² every 2 weeks and paclitaxel (225 mg/m² every 2 weeks with filgrastim and darbepoetin alfa, followed by capecitabine alone (dose levels 1 and 3 or with vinorelbine (dose levels 2 and 4. Capecitabine was given on days 1-14 every 21 days at 1000 or 1250 mg/m2 twice daily (dose levels 1/2 and 3/4, respectively. Vinorelbine 25 mg/m2 was given on days 1 and 8 of each 21-day course (dose levels 2 and 4. Results Fifty-one patients were treated. There was one dose-limiting toxicity (DLT at dose level 1. At dose level 2 (capecitabine and vinorelbine, five of 10 patients experienced DLTs. Therefore evaluation of vinorelbine was abandoned and dose level 3 (capecitabine monotherapy was expanded. Hand-foot syndrome and diarrhoea were dose limiting with capecitabine 1250 mg/m2 twice daily. At 35.2 months' median follow-up, the estimated 3-year relapse-free and overall survival rates were 82% and 91%, respectively. Conclusions Administration of capecitabine monotherapy after sequential dose-dense epirubicin and paclitaxel is feasible in node-positive EBC, while the combination of capecitabine and vinorelbine as used here caused more DLTs. Trial registration Current Controlled Trials ISRCTN38983527.

  19. Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2 in patients with metastatic malignant melanoma

    Directory of Open Access Journals (Sweden)

    Gillies Stephen D

    2009-07-01

    Full Text Available Abstract Background To explore the biological activity of EMD 273063 (hu14.18-IL2, a humanized anti-GD2 monoclonal antibody fused to interleukin-2 (IL2, in patients with unresectable, stage IV cutaneous melanoma as measured by induction of immune activation at the tumor site and in peripheral blood. Methods Nine patients were treated with 4 mg/m2 per day of EMD 273063 given as a 4-h intravenous infusion on days 1, 2, and 3 every four weeks (one cycle. Peripheral blood was analyzed for T cell and natural killer cell phenotype and frequency, as well as levels of soluble IL2 receptor (sIL2R, IL10, IL6, tumor necrosis factor alpha and neopterin. Biopsies of tumor metastasis were performed prior to therapy and at day 10 of the first 2 cycles to study lymphocyte accumulation by immunohistochemistry. Results Treatment was generally well tolerated and there were no study drug-related grade 4 adverse events. Grade 3 events were mainly those associated with IL2, most commonly rigors (3 patients and pyrexia (2 patients. Best response on therapy was stable disease in 2 patients. There were no objective tumor regressions by standard response criteria. Systemic immune activation was demonstrated by increases in serum levels of sIL2R, IL10, and neopterin. There was evidence of increased tumor infiltration by T cells, but not NK cells, in most post-dosing biopsies, suggesting recruitment of immune cells to the tumor site. Conclusion EMD 273063 demonstrated biologic activity with increased immune-related cytokines and intratumoral changes in some patients consistent with the suspected mechanism of action of this immunocytokine.

  20. Staging for vulvar cancer.

    Science.gov (United States)

    Hacker, Neville F; Barlow, Ellen L

    2015-08-01

    Vulvar cancer has been staged by the International Federation of Gynaecology and Obstetrics (FIGO) since 1969, and the original staging system was based on clinical findings only. This system provided a very good spread of prognostic groupings. Because vulvar cancer is virtually always treated surgically, the status of the lymph nodes is the most important prognostic factor and this can only be determined with certainty by histological examination of resected lymph nodes, FIGO introduced a surgical staging system in 1988. This was modified in 1994 to include a category of microinvasive vulvar cancer (stage IA), because such patients have virtually no risk of lymph node metastases. This system did not give a reasonably even spread of prognostic groupings. In addition, patients with stage III disease were shown to be a heterogeneous group prognostically, and the number of positive nodes and the morphology of those nodes were not taken into account. A new surgical staging system for vulvar cancer was introduced by FIGO in 2009. Initial retrospective analyses have suggested that this new staging system has overcome the major deficiencies in the 1994 system. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  1. Staging for vaginal cancer.

    Science.gov (United States)

    Rajaram, Shalini; Maheshwari, Amita; Srivastava, Astha

    2015-08-01

    Vaginal cancer is a rare cancer comprising about 3% of all gynecologic cancers. Primary vaginal cancer should be carefully assigned as spread from cervix, vulva, and other metastatic tumors to vagina can occur. Although vaginal cancer traditionally occurs in older postmenopausal women, the incidence of high-risk human papillomavirus (HPV)-induced cancers is increasing in younger women. Squamous cell carcinoma is still the most common histopathologic type followed by adenocarcinoma. With decreasing use of diethylstilbestrol in pregnancy, non-diethylstilbestrol-associated cancers are described. The Federation Internationale de Gynecologie et d'Obstetrique (FIGO) staging of vaginal cancer (2009) follows the same rules as cervical cancer; it is clinically staged and allows the use of routine investigative modalities for staging. Although FIGO encourages the use of advanced imaging modalities, such as computed tomography, magnetic resonance imaging (MRI), and positron emission tomography (PET), to guide therapy, the imaging findings may not be used to change or reassign the stage. TNM staging is the pathologic staging system proposed by the American Joint Committee on Cancer, and information available from examination of the resected specimen, including pelvic and inguinal lymph nodes, may be used for staging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Early-Stage Classic Hodgkin Lymphoma: The Utilization of Radiation Therapy and Its Impact on Overall Survival

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Rahul R., E-mail: rparikh@chpnet.org [Department of Radiation Oncology, Mount Sinai Beth Israel Medical Center and Mount Sinai St. Luke' s-Roosevelt Hospitals, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, New York (United States); Grossbard, Michael L. [Division of Hematology-Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York (United States); Harrison, Louis B. [Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Yahalom, Joachim [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2015-11-01

    Purpose: To examine the association between radiation therapy (RT) utilization and overall survival (OS) for patients with early-stage Hodgkin lymphoma (HL). Methods and Materials: Using the National Cancer Database, we evaluated clinical features and survival outcomes among patients diagnosed with stage I/II HL from 1998 to 2011. The association between RT use, covariables, and outcome was assessed in a Cox proportional hazards regression model. Propensity score matching was performed to balance observed confounding factors. Survival was estimated using the Kaplan-Meier method. Results: Among the 41,943 patients in the National Cancer Database with stage I/II HL, 29,752 patients were analyzed for this study. Radiation therapy use was associated with younger age (≤40 years), favorable insured status, higher socioeconomic status (income, education), and treatment at comprehensive community cancer centers (all P<.05). Five-year OS for patients receiving RT was 94.5%, versus 88.9% for those not receiving RT (P<.01). Radiation therapy use was a significant predictor of OS in the “As-Treated” cohort (hazard ratio 0.53, 95% confidence interval 0.49-0.58, P<.01) and intention-to-treat analysis (P<.01). After propensity score matching based on clinicopathologic characteristics, RT use remained associated with improved OS (hazard ratio 0.46, 95% confidence interval 0.38-0.56, P<.01). Over the study period, RT utilization for this cohort decreased from 55% to 44%, most commonly because it was not part of the planned initial treatment strategy. Conclusions: Consolidation RT was associated with improved OS for patients with early-stage classic HL. We also have identified patient-specific variations in the use of RT that may be targeted to improve patient access to care.

  3. Staged bilateral carotid endarterectomy

    DEFF Research Database (Denmark)

    Schroeder, T; Sillesen, H; Engell, Hans Christian

    1986-01-01

    In a series of 56 staged bilateral carotid endarterectomies, new neurologic symptoms developed in 5% and 20% following the first and second procedure, respectively. All complications were transient or minor. The incidence of postendarterectomy hypertension was significantly higher following...... the second procedure, when operations were staged less than 3 weeks apart. A correlation between these hypertensive episodes and the occurrence of new neurologic symptoms could not be shown. However, as this correlation has been proved in several other reports, bilateral carotid endarterectomy is advised...... to be staged at least 3 weeks apart. In addition, a conservative attitude towards contralateral asymptomatic lesions is proposed....

  4. Staging of lung cancer.

    Science.gov (United States)

    de Groot, Patricia M; Carter, Brett W; Betancourt Cuellar, Sonia L; Erasmus, Jeremy J

    2015-06-01

    Primary lung cancer is the leading cause of cancer mortality in the world. Thorough clinical staging of patients with lung cancer is important, because therapeutic options and management are to a considerable degree dependent on stage at presentation. Radiologic imaging is an essential component of clinical staging, including chest radiography in some cases, computed tomography, MRI, and PET. Multiplanar imaging modalities allow assessment of features that are important for surgical, oncologic, and radiation therapy planning, including size of the primary tumor, location and relationship to normal anatomic structures in the thorax, and existence of nodal and/or metastatic disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Staging Mobilities / Designing Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    2015-01-01

    In recent years, urban research has taken a ‘mobilities turn’. There has been a developing realisation that mobilities do not ‘just happen.’ Mobilities are carefully and meticulously designed, planned and staged (from above). However, they are equally importantly acted out, performed and lived...... asks: what are the physical, social, technical, and cultural conditions to the staging of contemporary urban mobilities? The theoretical framing in the Staging mobilities book is applied to four in-depth cases in the accompanying volume Designing mobilities.This book explore how places, sites...

  6. Stages of Colon Cancer

    Science.gov (United States)

    ... types of surgery : Local excision or simple polypectomy . Resection and anastomosis . This is done when the tumor is too ... stage I colon cancer usually includes the following: Resection and anastomosis . Use our clinical trial search to find NCI- ...

  7. Stages of Labor

    Science.gov (United States)

    ... Moms Need Blog News & Media News Videos Mission stories Ambassadors Spotlights Tools & Resources Frequently asked media questions ... can be born. This stage can last as short as 20 minutes or as long as several ...

  8. Multiple Stages 2

    DEFF Research Database (Denmark)

    Andreasen, John

    Multiple stages 2: theatrical futures, set design, community plays, cultural capitals, democracy & drama, WWII dramas, performance on adoption, promenade about emigration, qualities in political theatre, performance analysis, dramaturgical education, Toulmin Variations...

  9. Stages of Esophageal Cancer

    Science.gov (United States)

    ... the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds , ... stage of the cancer being treated. External and internal radiation therapy are used to treat esophageal cancer. A plastic ...

  10. Stages of Anal Cancer

    Science.gov (United States)

    ... the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds , ... stage of the cancer being treated. External and internal radiation therapy are used to treat anal cancer. Chemotherapy Chemotherapy ...

  11. Stages of Penile Cancer

    Science.gov (United States)

    ... the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds , ... stage of the cancer being treated. External and internal radiation therapy are used to treat penile cancer. Chemotherapy Chemotherapy ...

  12. Staging interrail mobilities

    DEFF Research Database (Denmark)

    Jensen, Martin Trandberg; Gyimóthy, Szilvia; Jensen, Ole B.

    2016-01-01

    This article applies the multiscalar ‘staging mobilities’ framework from the emergent subfield of mobilities design to analyse an enduring European rail travel phenomenon, interrail. This discussion extends and contributes to tourism mobilities research. Second, the article enriches previous...

  13. Stages of ores formation

    International Nuclear Information System (INIS)

    Khasanov, A.Kh.

    1988-01-01

    Deposit formation (especially endogenous) is the complicated, multi-stage and long process. Establishment of deposit formation succession, age-specific correlations of minerals and aggregates have a high importance at solving genetic questions. Studying of minerals correlations and mineral aggregates, succession of their crystallization and other observations let restore the history of deposit formation, pick up in it different on duration and physical and chemical conditions stages

  14. Colorectal cancer and the 7th revision of the TNM staging system: review of changes and suggestions for uniform pathologic reporting.

    Science.gov (United States)

    Obrocea, F L; Sajin, Maria; Marinescu, Elena Cristina; Stoica, D

    2011-01-01

    Colorectal cancer (CRC) is a neoplastic disease with a continuously growing incidence in Romania and throughout the world. Although the surgery remains the first line treatment for most of the cases, newly discovered targeted molecular therapies - effective for some patients, but with various side effects and significant financial burden for the national health systems - requires not only stratification of patients in prognostic groups but also evaluation of some non-anatomic factors with major impact on the prognosis and therapeutic strategy. The AJCC/UICC TNM staging system, in his 7th revision, effective for cases diagnosed on or after January 1, 2010, responds to these needs. On the other hand, the role of the pathologist is increasing in terms of workload and amount of information to be included in the pathology report in order to deliver a personalized diagnosis. There are concerns worldwide regarding relevance, validity and completeness of pathologic reporting of CRC in the absence of a uniform reporting format. Therefore, suggestions for a standardized pathology report of CRC are made, based on TNM 7 and recent, up-to-date conclusive published data.

  15. CCDC22 gene polymorphism is associated with advanced stages of endometriosis in a sample of Brazilian women.

    Science.gov (United States)

    de Oliveira Francisco, Daniela; de Paula Andres, Marina; Gueuvoghlanian-Silva, Bárbara Yasmim; Podgaec, Sergio; Fridman, Cintia

    2017-07-01

    Based on the assumption that genetic factors are involved in the etiology of endometriosis, this study aimed to investigate the possibility of rs498679 (TLR4 gene), rs1799964 (TNF-α gene), rs3024496 (IL-10 gene), and rs2294021 (CCDC22 gene) polymorphisms being associated with the occurrence of this disease in a sample of Brazilian women. We conducted a case-control study with 100 women with histological confirmation of endometriosis (endometriosis group) and 100 women submitted to laparoscopy for benign disorders, in which the absence of endometriosis was confirmed (control group). All samples were genotyped by real-time PCR technique for rs498679, rs1799964, rs3024496, and rs2294021 polymorphisms. No significant difference was observed in genotypic or allelic frequencies between control and endometriosis groups for rs498679 (TLR4 gene), rs1799964 (TNF-α gene), rs3024496 (IL-10 gene), neither when comparing endometriosis subgroups (I-II versus III-IV). On the other hand, significant difference between stages I-II and III-IV of the disease was found in genotypic and allelic frequencies for the rs2294021 (CCDC22 gene) SNP (p = 0.048 and p = 0.017, respectively). Our results suggest that the rs2294021 (CCDC22 gene) polymorphism could be associated with increased susceptibility to endometriosis in Brazilian women when the allele C is present. In order to clarify this result, further studies should be conducted on a larger population.

  16. Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

    Science.gov (United States)

    2017-05-03

    Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  17. REVIEW OF THE NEGOTIATION OF THE MODEL PROTOCOL ADDITIONAL TO THE AGREEMENT(S) BETWEEN STATE(S) AND THE INTERNATIONAL ATOMIC ENERGY AGENCY FOR THE APPLICATION OF SAFEGUARDS,INFCIRC/540 (Corrected) VOLUME I/III SETTING THE STAGE: 1991-1996.

    Energy Technology Data Exchange (ETDEWEB)

    Rosenthal, M.D.; Saum-Manning, L.; Houck, F.; Anzelon, G.

    2010-01-01

    Events in Iraq at the beginning of the 1990s demonstrated that the safeguards system of the International Atomic Energy Agency (IAEA) needed to be improved. It had failed, after all, to detect Iraq's clandestine nuclear weapon program even though some of Iraq's's activities had been pursued at inspected facilities in buildings adjacent to ones being inspected by the IAEA. Although there were aspects of the implementation of safeguards where the IAEA needed to improve, the primary limitations were considered to be part of the safeguards system itself. That system was based on the Nuclear Nonproliferation Treaty of 1970, to which Iraq was a party, and implemented on the basis of a model NPT safeguards agreement, published by the IAEA 1972 as INFCIRC/153 (corrected). The agreement calls for states to accept and for the IAEA to apply safeguards to all nuclear material in the state. Iraq was a party to such an agreement, but it violated the agreement by concealing nuclear material and other nuclear activities from the IAEA. Although the IAEA was inspecting in Iraq, it was hindered by aspects of the agreement that essentially limited its access to points in declared facilities and provided the IAEA with little information about nuclear activities anywhere else in Iraq. As a result, a major review of the NPT safeguards system was initiated by its Director General and Member States with the objective of finding the best means to enable the IAEA to detect both diversions from declared stocks and any undeclared nuclear material or activities in the state. Significant improvements that could be made within existing legal authority were taken quickly, most importantly a change in 1992 in how and when and what design information would be reported to the IAEA. During 1991-1996, the IAEA pursued intensive study, legal and technical analysis, and field trials and held numerous consultations with Member States. The Board of Governors discussed the issue of strengthening safeguards at almost all of its meeting.

  18. Incorporating Tumor Characteristics to the American Joint Committee on Cancer Breast Cancer Staging System.

    Science.gov (United States)

    Chavez-MacGregor, Mariana; Mittendorf, Elizabeth A; Clarke, Christina A; Lichtensztajn, Daphne Y; Hunt, Kelly K; Giordano, Sharon H

    2017-11-01

    The American Joint Committee on Cancer (AJCC) breast cancer staging system provides important prognostic information. The recently published eighth edition incorporates biological markers and recommends the use of a complex "prognostic stage." In this study, we assessed the relationship between stage, breast cancer subtype, grade, and outcome in a large population-based cohort and evaluated a risk score system incorporating tumor characteristic to the AJCC anatomic staging system. Patients diagnosed with primary breast cancer stage I-IV between 2005-2008 were identified in the California Cancer Registry. For patients with stage I-III disease, pathologic stage was recorded. For patients with stage IV disease, clinical stage was utilized. Five-year breast cancer specific survival (BCSS) and overall survival (OS) rates were determined for each potential tumor size-node involvement-metastases (TNM) combination according to breast cancer subtype. A risk score point-based system using grade, estrogen receptor, and human epidermal growth factor receptor 2 (HER2) status was designed to complement the anatomic AJCC staging system. Survival probabilities between groups were compared using log-rank test. Cox proportional hazards models were used. Among 43,938 patients, we observed differences in 5-year BCSS and OS for each TNM combination according to breast cancer subtype. The most favorable outcomes were seen for hormone receptor-positive tumors followed closely by HER2-positive tumors, with the worst outcomes observed for triple negative breast cancer. Our risk score system separated patients into four risk groups within each stage category (all p  system incorporates biological factors into the AJCC anatomic staging system, providing accurate prognostic information. This study demonstrates that stage, but also breast cancer subtype and grade, define prognosis in a large population of breast cancer patients. It shows that a point-based risk score system that incorporates

  19. Staging of extrahepatic cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yong Eun; Choi, Jin-Young [Yonsei University College of Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science, Seoul (Korea); Kim, Myeong-Jin [Yonsei University College of Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science, Seoul (Korea); Yonsei University College of Medicine, Institute of Gastroenterology, Yonsei (Korea); Yonsei University Health System, Department of Diagnostic Radiology, Seoul (Korea); Park, Young Nyun [Yonsei University College of Medicine, Institute of Gastroenterology, Yonsei (Korea); Yonsei University College of Medicine, Department of Pathology, Yonsei (Korea); Lee, Yoon-Hee [Yonsei University College of Medicine, Department of Pathology, Yonsei (Korea)

    2008-10-15

    Preoperative staging of extrahepatic cholangiocarcinoma is important in determining the best treatment plan. Several classification systems have been suggested to determine the operability and extent of surgery. Longitudinal tumor extent is especially important in extrahepatic cholangiocarcinoma because operative methods differ depending on the tumor extent. The Bismuth-Corlette classification system provides useful information when planning for surgery. However, this classification system is not adequate for selecting surgical candidates. Anatomic variation of the bile duct and gross morphology of the tumor must be considered simultaneously. Lateral spread of the tumor can be evaluated based on the TNM staging provided by American Joint Committee on Cancer (AJCC). However, there is a potential for ambiguity in the distinction of T1 and T2 cancer from one another. In addition, T stage does not necessarily mean invasiveness. Blumgart T staging is helpful for the assessment of resectability with the consideration of nodal status and distant metastasis as suggested by the AJCC cancer staging system. Computed tomography (CT) and magnetic resonance imaging (MRI) are the primary tools used in the assessment of longitudinal and lateral spread of a tumor when determining respectability. Diagnostic laparoscopy and positron emission tomography (PET) may play additional roles in this regard. (orig.)

  20. Composers on stage

    DEFF Research Database (Denmark)

    Groth, Sanne Krogh

    A trend on the scene of contemporary music is composers going on stage, performing their pieces themselves. Within a discourse of popular music, this is more the rule than exception, but when it comes to the context of contemporary scored music, the historical and aesthetic context differs......, and something quite different is undergoing. This paper intends to discuss three examples of performances in which the composer’s appearance on stage was an important part of the piece, - both when it came to the role as a performer and as an individual person – as representer and presenter. The paper intends...... to rise the following questions: What happens to the status of the author, when he suddenly (re-)appears on stage? How is this appearance to be understood in both a contemporary and historical context: Is it the musical virtuous appearing again, are we witnessing musical works turning...

  1. Survival prognostic value of morphological and metabolic variables in patients with stage I and II non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Domachevsky, L. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Beilinson Hospital, Petah Tikva (Israel); Groshar, D.; Bernstine, H. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Galili, R. [Lady Davis-Carmel Medical Center, Department of Cardiothoracic Surgery, Haifa (Israel); Saute, M. [Rabin Medical Center, Department of Cardiothoracic Surgery, Petah Tiqva (Israel)

    2015-11-15

    The prognosis of patients with non-small cell lung cancer (NSCLC) is important, as patients with resectable disease and poor prognostic variables might benefit from neoadjuvant therapy. The goal of this study is to evaluate SUVmax, SUVmax ratio, CT volume (CTvol), metabolic tumour volume (MTV) and total lesion glycolisis (TLG) as survival prognostic markers. In addition, we defined two variables; MTV x SUVmax (MTVmax) and CTvol x SUVmax (CTvolmax) and assessed whether they can be used as prognostic markers. Patients with stage I-II NSCLC who underwent 18 F FDG PET/CT and surgery were evaluated. Cox proportional-hazard model was used to determine the association between variables and survival. Similar analysis was performed in cases with no lymph node (LN) involvement. One hundred and eighty-one patients were included (at the end of the study, 140 patients were alive). SUVmax with a cut-off value of 8.2 was significant survival prognostic factor regardless of LN involvement (P = 0.012). In cases with no LN involvement, SUVmax and CTvol (≥7.1 ml) were significant survival prognostic factors with P = 0.004 and 0.03, respectively. SUVmax may be a useful prognostic variable in stage I-II NSCLC while morphologic tumour volume might be useful in cases with no lymph node involvement. (orig.)

  2. Staging Collaborative Innovation Processes

    DEFF Research Database (Denmark)

    Pedersen, Signe; Clausen, Christian

    Organisations are currently challenged by demands for increased collaborative innovation internally as well as with external and new entities - e.g. across the value chain. The authors seek to develop new approaches to managing collaborative innovative processes in the context of open innovation...... and public private innovation partnerships. Based on a case study of a collaborative design process in a large electronics company the paper points to the key importance of staging and navigation of collaborative innovation process. Staging and navigation is presented as a combined activity: 1) to translate...

  3. Comparison between established and the Worldwide Esophageal Cancer Collaboration staging systems.

    Science.gov (United States)

    Gaur, Puja; Hofstetter, Wayne L; Bekele, B Nebiyou; Correa, Arlene M; Mehran, Reza J; Rice, David C; Roth, Jack A; Vaporciyan, Ara A; Rice, Thomas W; Swisher, Stephen G

    2010-06-01

    Controversy exists regarding the optimal staging system for patients with gastroesophageal junction adenocarcinoma (GEJA). The Worldwide Esophageal Cancer Collaboration (WECC) has organized a multi-institutional database from which a novel esophageal staging system has been organized. We used a single institution experience to validate the hypothesis that the WECC system more accurately predicts survival in GEJA patients than both the American Joint Commission on Cancer 6th edition esophageal and gastric systems. We reviewed 449 GEJA patients (Siewert I-III) treated with neoadjuvant therapy followed by surgery or surgery-alone between 1990 and 2007. A blinded statistician performed a head-to-head comparison regarding the ability of each staging system to predict survival. A subgroup analysis of patients who underwent surgery only (n = 176) was also performed. All three systems predicted survival of patients with GEJA. However, a Bayesian variable selection model found that the WECC system was better than both American Joint Commission on Cancer esophageal and gastric systems (probability 0.99 and 0.98, respectively). Subset analysis suggested that the WECC staging was also optimum for predicting survival in surgery-alone patients. While the esophageal staging system is better at predicting survival than the gastric staging system, the WECC system may be the most favorable single-system predictor of survival for patients with resected GEJA. As suggested by the WECC system, incorporating the number of positive lymph nodes within the staging system may present an advantage in predicting survival. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Are stage IV vestibular schwannomas preoperatively different from other stages?

    Science.gov (United States)

    Tringali, Stéphane; Dubreuil, Christian; Zaouche, Sandra; Ferber-Viart, Chantal

    2008-01-01

    The aim of this study was to focus on the clinical and paraclinical symptoms of patients suffering from Stage IV vestibular schwannomas (VSs). In this prospective study, we included 734 patients who have VS and candidates for operation. Patients were classified as having Stage I, II, III, or IV tumors according to Tos criteria as evaluated by magnetic resonance imaging. PREOPERATIVE CLINICAL EVALUATION: We recorded the occurrence of complaints (%) and duration (yr) of hearing loss, tinnitus, and balance disorder. Preoperative paraclinical evaluation included pure-tone (PTA) and speech audiometry, auditory brainstem response (ABR) patterns, and vestibular deficit at videonystamography (VNG). Continuous variables were compared between Stage IV and other stages using analysis of variance. Qualitative variables expressed as a percentage of presence were compared between Stage IV and other stages using percentage comparison. Quantitative Parameters. Patients with Stage IV VS were significantly younger as compared with patients with other stages. Stage IV hearing loss was greater compared with other stages at 250 and 500 Hz but smaller at 2,000 and 8,000 Hz. We found no difference in the loss of PTA between Stage IV and the other stages. Speech discriminancy score was smaller in Stage IV. The durations of hearing loss, tinnitus, and balance disorders were similar whatever the tumor stage. Auditory brainstem response patterns showed no difference in Wave III latency between Stage IV VS and other stages, whereas Wave V latency and V-I interval were higher in Stage IV. Both ABR threshold and VNG caloric deficit were higher in Stage IV VS compared with other stages. Qualitative Parameters. The percentage of patients with Stage IV was lower than that with Stages II and III. The percentage of men and women was similar in all stages. The occurrence of hearing loss was similar in all stages, whereas that of tinnitus was lower in Stage IV compared with Stages I and II. In

  5. End-stage kidney disease

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000500.htm End-stage kidney disease To use the sharing features on this page, please enable JavaScript. End-stage kidney disease (ESKD) is the last stage of long-term ( ...

  6. Stage theta pinch experiments

    International Nuclear Information System (INIS)

    Linford, R.K.; Downing, J.N.; Gribble, R.F.; Jacobson, A.R.; Platts, D.A.; Thomas, K.S.

    1975-01-01

    The Staged Theta Pinch program is designed to study the technological and physics problems associated with producing fat plasmas and separating the implosion heating from the adiabatic compression. Several methods of implosion heating are discussed. Circuit diagrams and theoretical magnetic field behavior are described for the STP and resonant heating experiments. (MOW)

  7. "Stage 40" Handbook.

    Science.gov (United States)

    Mill River Union High School, North Clarendon, VT.

    The policies, purposes, and guidelines of "Stage 40," an educational repertory company for students, are presented in this paper, which also explains how the company functions. The paper discusses the company's history, the relationship between the company and academics, and the responsibilities of a company member. Letters by the board…

  8. World Stage Design

    Index Scriptorium Estoniae

    2005-01-01

    12-19. III Torontos rahvusvaheline lavakujunduse, kostüümi ning valgus- ja helikujunduse näitus, mis toimub samaaegselt OISTATi (International Organization of Scenographers, Theatre Architects and Technicians) maailmakongressiga ja USITT (United States Institute for Theatre Technology) üritustega (konverents, Stage Expo). Eestit esindab lavakujunduse kategoorias Lilja Blumenfeld-Luhse

  9. Linac project - actual stage

    International Nuclear Information System (INIS)

    Carlin Filho, N.

    1990-01-01

    The actual development stage of Pelletron accelerator to study heavy ion reactions, nuclear structures and applied nuclear physics is presented. The construction of acceleration systems able to provide beams of several mass and energies up to 20 MeV/A, is discussed, describing acceleration structures and implemented systems. (M.C.K.)

  10. stage/page/play

    DEFF Research Database (Denmark)

    context. Contributors: Per Brask, Dario Fo, Jette Barnholdt Hansen, Pil Hansen, Sven Åke Heed, Ulla Kallenbach, Sofie Kluge, Annelis Kuhlmann, Kela Kvam, Anna Lawaetz, Bent Flemming Nielsen, Franco Perrelli, Magnus Tessing Schneider, Antonio Scuderi. stage/page/play is published as a festschrift...

  11. [Risk factors for anemia in the early stages of chronic kidney disease].

    Science.gov (United States)

    Milovanov, Yu S; Kozlovskaya, L V; Milovanova, L Yu; Markina, M M; Kozlov, V V; Taranova, M V; Fomin, V V

    To identify the early markers of anemia in chronic kidney disease (CKD) in patients with chronic glomerulonephritis (CGN) and glomerulonephritis (GN) in systemic diseases. Seventy-nine patients with some male preponderance who were aged 21 to 65 years (45.3±11.1 years) and had CKD (CGN and GN) in systemic diseases (systemic lupus erythematosus and Wegener's granulomatosis) in the early stages (Stages I-II) of CKD were examined. GN was diagnosed by a lifetime renal biopsy. Systemic diseases were diagnosed according to the criteria for each nosological entity. The stages of CKD were defined according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria; the glomerular filtration rate (GFR) was calculated using the CKD EPI equation (2012). According to the presence or absence of anemia, all the patients included in the study were divided into 2 groups: 1) 43 (54.4%) anemic patients; 2) 36 (45.6%) non-anemic patients (a control group). In addition to general clinical examination adopted for a nephrology department, special studies, such as determination of the serum levels of hepcidin, interferon-γ (IFN-γ), soluble Klotho protein (s-Klotho), as well as iron, ferritin, and transferrin saturation (TSAT) ratio, were performed to solve the set tasks. Forty-three anemic patients who had a hemoglobin level of 110 (100; 119) g/l and 36 control patients who had the similar values were noted to have statistically significantly (panemia were also found to have a statistically significantly (panemia, its detection rate in the presence of systemic diseases was 3.2 times higher than that in CGN patients (41.7 and 12.7%). ROC analysis revealed that in the CKD patients with CGN and GN, the serum hepcidin level ≥ 25 ng/ml, with the sensitivity and specificity being of 89.7% and 74%, respectively (p > 0.001), was associated with the development of anemia. Moreover, the hemoglobin level ofdiseases, elevated serum hepcidin levels should be regarded as a predictor

  12. Involved Node Radiation Therapy: An Effective Alternative in Early-Stage Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Maraldo, Maja V., E-mail: dra.maraldo@gmail.com [Department of Radiation Oncology, The Finsen Center, Rigshospitalet, Copenhagen (Denmark); Aznar, Marianne C. [Department of Radiation Oncology, The Finsen Center, Rigshospitalet, Copenhagen (Denmark); Faculty of Health Sciences, University of Copenhagen, Copenhagen (Denmark); Vogelius, Ivan R.; Petersen, Peter M. [Department of Radiation Oncology, The Finsen Center, Rigshospitalet, Copenhagen (Denmark); Specht, Lena [Department of Radiation Oncology, The Finsen Center, Rigshospitalet, Copenhagen (Denmark); Faculty of Health Sciences, University of Copenhagen, Copenhagen (Denmark)

    2013-03-15

    Purpose: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy in a cohort of 97 clinical stage I-II HL patients. Methods and Materials: Patients were staged with positron emission tomography/computed tomography scans, treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and given INRT (prechemotherapy involved nodes to 30 Gy, residual masses to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. Results: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7 malignancies were diagnosed, and 5 patients developed heart disease. Conclusions: INRT offers excellent tumor control and represents an effective alternative to more extended radiation therapy in the combined modality treatment for early-stage HL.

  13. RB research nuclear reactor - Annual report for 1985, I - III

    International Nuclear Information System (INIS)

    Markovic, H.; Pesic, M.; Vranic, S.; Petronijevic, M.; Jevremovic, M.; Ilic, I.

    1985-01-01

    This paper describes the operation of the RB reactor during 1985. The report includes 3 parts: Engineering description and operation of the RB reactor, reactor components and maintenance, and RB reactor utilization in 1985 [sr

  14. Maailma sporthobuste kasvatajad Inglismaal. I-II osa / Raigo Kollom

    Index Scriptorium Estoniae

    Kollom, Raigo, 1936-

    2013-01-01

    Maailma Sporthobuste Kasvatajate Föderatsiooni peaassambleel Inglismaal Newmarketi väikelinnas toimunud külastustest British Racing School'i, British Racing Museum'i ning Dubai valitseja ja Araabia Ühinenud Emiraatide asepresidendi šeik Mohammed bin Rashid Al Maktoumi hobusekasvandusse Darley Stud

  15. Crack Tip Flipping Under Mode I/III Tearing

    DEFF Research Database (Denmark)

    Felter, Christian Lotz; Specht Jensen, Lasse; Nielsen, Kim Lau

    Crack tip flipping, where the fracture surface alternates from side to side in 45° shear bands, seems to be an overlooked propagation mode in Mode I sheet tearing often disregarded as  “transitional” or tied to randomness in the material. In fact, such observations rarely make it to the literature....... However, crack tip flipping is a true propagation mode, but unlike those already established: i) it never settles in a steady-state as the near tip stress/strain field continuously change, and ii) the mechanism governing failure evolves behind the leading crack tip. Recent research has revealed new...... insight into this intriguing behavior of a crack propagating by the void nucleation and growth mechanism, and the work presented compiles both published and unpublished experimental and numerical findings. E.g. in a recent attempt to gain control of the flipping crack a slight Mode III was imposed...

  16. Problems of Air Defense - and - Appedicies. Volumes I-III

    Science.gov (United States)

    1951-08-01

    as Canada, the United Kingdom, Japan , and North Africa. Some parts of the recornmm-endJadions are adantable to sitiiations in field armies and the...question of economy of fili-ii it seemis desirable to rec- ommnend limited use of the photographiic scheme. 11n Lertain areas, and -at cer- tain times of...designating ce-rtain officers ’for engineerling duty * only"’ ( EDO ). Corresponding designations of noncommissioned and warrant officers would round

  17. Nordic Noir on Television: The Killing I-III

    DEFF Research Database (Denmark)

    Agger, Gunhild

    2012-01-01

    politics and the domestic levels in the first season of the series, to the focus on foreign politics with domestic dimensions in the second season, and the reversion to domestic politics, this time combined to a global dimension, in the last season. Similarities and differences in the plots...

  18. Susiseb ja podiseb I-II / Mihkel Mutt

    Index Scriptorium Estoniae

    Mutt, Mihkel, 1953-

    1998-01-01

    Järg: 27. märts. 1998. a. riigi kultuuripreemiate jagamisest; Eesti Draamateatrist. Vastukajad: Kasterpalu, Margus. Marutõbine teatripäev // Postimees (1998) 30. märts, lk. 15; Aarma, Jüri. Kolm tähelepanekut susisemise ja podisemise asjus // Sõnumileht (1998) 18. apr., lk. 15; Kordemets, Gerda. Pind põues või palk silmas // Sõnumileht (1998) 18. apr., lk. 15

  19. RB research nuclear reactor - Annual report for 1986, I - III

    International Nuclear Information System (INIS)

    Markovic, H.; Pesic, M.; Vranic, S.; Petronijevic, M.; Jevremovic, M.; Ilic, I.

    1987-01-01

    This report includes data concerning the RB reactor operation in 1986, state of the reactor components, data about the employed personnel and the database of experimental and other reactor related devices. It is made of 3 parts: Engineering description and operation of the RB reactor including dosimetry, reactor staff data and financial report; Reactor facility components and maintenance; RB reactor operation and utilization in 1986 [sr

  20. RB research nuclear reactor, Annual report for 1989, I - III

    International Nuclear Information System (INIS)

    Stefanovic, D.; Pesic, M.; Hadimahmutovic, N.; Vranic, S.; Petronijevic, M.; Jevremovic, M.; Ilic, I.

    1989-12-01

    This report is made of three parts. Part one contains a short description of the reactor, reactor operation, incidents, status of reactor equipment and components (nuclear fuel, heavy water, reactor vessel, heavy water circulation system, electronic, electric and mechanical equipment, auxiliary systems and Vax-8250 computer). It includes dosimetry and radiation protection data, personnel and financial data. Second part of this report in concerned with maintenance of reactor components and instrumentation. Part three includes data about reactor utilization during 1989

  1. WBFSH aastakoosolek Varssavis. I-II osa / Raigo Kollom

    Index Scriptorium Estoniae

    Kollom, Raigo, 1936-

    2013-01-01

    Poolas 7.-9. oktoobrini Maailma Sporthobuste Kasvatajate Föderatsiooni peaassambleel toimunust ning loengutest ja aruteludest: Hobuste "genoomilisest aretusest", Jõudluskontrolli ja terviseandmete kasutamisest Rootsi aretuses, Hobuste lineaarse kirjeldamise meetodist, tõuraamatute tulevikust. Teises osas: Hobusekasvatuse seisust Poolas, Janow Podlaski hobusekasvatusest ja üldisest eluolust

  2. Staging Collaborative Innovation Processes

    DEFF Research Database (Denmark)

    Pedersen, Signe; Clausen, Christian

    Organisations are currently challenged by demands for increased collaborative innovation internally as well as with external and new entities - e.g. across the value chain. The authors seek to develop new approaches to managing collaborative innovative processes in the context of open innovation...... and public private innovation partnerships. Based on a case study of a collaborative design process in a large electronics company the paper points to the key importance of staging and navigation of collaborative innovation process. Staging and navigation is presented as a combined activity: 1) to translate...... the diverse matters of concern into a coherent product or service concept, and 2) in the same process move these diverse holders of the matters of concern into a translated actor network which carry or support the concept....

  3. Staging Sociotechnical Spaces

    DEFF Research Database (Denmark)

    Clausen, Christian; Yoshinaka, Yutaka

    2007-01-01

    The management of innovation and product development is increasingly facing complex challenges of staging design processes across heterogeneous organisational spaces, with multiple actor-concerns and sources of knowledge. This paper addresses how insights from the Actor-Network Theory and political...... process theory may contribute to a reflexive understanding of design as the staging of socio-technical relations and processes cutting across boundaries of diverse organisational, political and knowledge domains. This idea is pursued through the notion of ‘socio-technical spaces’. Socio-technical space...... of product development. The concept of socio-technical spaces is further illustrated through actual examples from industry dealing with early conceptualisation in product development and the role played by management concepts in the configuration of spaces....

  4. Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

    Directory of Open Access Journals (Sweden)

    Skirnisdottir Ingiridur

    2012-09-01

    Full Text Available Abstract Background Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Methods Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. Results The most significant differences (p  Conclusions The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.

  5. Calibration of Nanopositioning Stages

    Directory of Open Access Journals (Sweden)

    Ning Tan

    2015-12-01

    Full Text Available Accuracy is one of the most important criteria for the performance evaluation of micro- and nanorobots or systems. Nanopositioning stages are used to achieve the high positioning resolution and accuracy for a wide and growing scope of applications. However, their positioning accuracy and repeatability are not well known and difficult to guarantee, which induces many drawbacks for many applications. For example, in the mechanical characterisation of biological samples, it is difficult to perform several cycles in a repeatable way so as not to induce negative influences on the study. It also prevents one from controlling accurately a tool with respect to a sample without adding additional sensors for closed loop control. This paper aims at quantifying the positioning repeatability and accuracy based on the ISO 9283:1998 standard, and analyzing factors influencing positioning accuracy onto a case study of 1-DoF (Degree-of-Freedom nanopositioning stage. The influence of thermal drift is notably quantified. Performances improvement of the nanopositioning stage are then investigated through robot calibration (i.e., open-loop approach. Two models (static and adaptive models are proposed to compensate for both geometric errors and thermal drift. Validation experiments are conducted over a long period (several days showing that the accuracy of the stage is improved from typical micrometer range to 400 nm using the static model and even down to 100 nm using the adaptive model. In addition, we extend the 1-DoF calibration to multi-DoF with a case study of a 2-DoF nanopositioning robot. Results demonstrate that the model efficiently improved the 2D accuracy from 1400 nm to 200 nm.

  6. Role of serum carcinoembryonic antigen in the detection of colorectal cancer before and after surgical resection

    Science.gov (United States)

    Su, Bin-Bin; Shi, Hui; Wan, Jun

    2012-01-01

    AIM: To determine whether serum levels of carcinoembryonic antigen (CEA) correlate with the presence of primary colorectal cancer (CRC), and/or recurrent CRC following radical resection. METHODS: A total of 413 patients with CRC underwent radical surgery between January 1998 and December 2002 in our department and were enrolled in this study. The median follow-up period was 69 mo (range, 3-118 mo), and CRC recurrence was experienced by 90/413 (21.8%) patients. Serum levels of CEA were assayed preoperatively, and using a cutoff value of 5 ng/mL, patients were divided into two groups, those with normal serum CEA levels (e.g., ≤ 5 ng/mL) and those with elevated CEA levels (> 5 ng/mL). RESULTS: The overall sensitivity of CEA for the detection of primary CRC was 37.0%. The sensitivity of CEA according to stage, was 21.4%, 38.9%, and 41.7% for stages I-III, respectively. Moreover, for stage II and stage III cases, the 5-year disease-free survival rates were reduced for patients with elevated preoperative serum CEA levels (P < 0.05). The overall sensitivity of CEA for detecting recurrent CRC was 54.4%, and sensitivity rates of 36.6%, 66.7%, and 75.0% were associated with cases of local recurrence, single metastasis, and multiple metastases, respectively. In patients with normal serum levels of CEA preoperatively, the sensitivity of CEA for detecting recurrence was reduced compared with patients having a history of elevated CEA prior to radical resection (32.6% vs 77.3%, respectively, P < 0.05). CONCLUSION: CRC patients with normal serum CEA levels prior to resection maintained these levels during CRC recurrence, especially in cases of local recurrence vs cases of metastasis. PMID:22563201

  7. Importance of physical examination in the absence of a mammographic abnormality for the detection of early-stage breast cancer.

    Science.gov (United States)

    Diratzouian, Hasmik; Freedman, Gary M; Hanlon, Alexandra L; Eisenberg, Debra F; Anderson, Penny R

    2005-10-01

    A recent trial called into question the efficacy of breast self-examination. We studied the characteristics and outcome of women in whom physical examination (PE) was their sole method of breast cancer detection. From 1970 to 1998, 1752 women with stage I/II breast cancer underwent breast-conserving surgery and radiation. Two hundred sixty patients (15%) had abnormal PE finding as their sole method of cancer detection at the time of diagnosis, 723 (41%) had only mammographic findings, and 762 (43%) had both. Detection by PE was associated with younger age, larger tumor size, positive axillary nodes, and use of chemotherapy. For women Physical examination remains an important method of detection of breast cancer, particularly for younger women for whom mammography is less sensitive and not performed as frequently.

  8. A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer.

    Science.gov (United States)

    Xu, Ling; Li, Jiang-Hong; Ye, Jing-Ming; Duan, Xue-Ning; Cheng, Yuan-Jia; Xin, Ling; Liu, Qian; Zhou, Bin; Liu, Yin-Hua

    2017-08-20

    Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer (AJCC) expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analyses. This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival (DFS) of 769 Stage I-III patients was 89.7%, and the 5-year overall survival (OS) of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups. There were 372 cases (46.7%) assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS (χ2 = 11.319, P= 0.001) and 5-year OS (χ2 = 5.225, P= 0.022). In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS (χ2 = 6.510, P= 0.039) but no significant differences in 5-year OS (χ2 = 5.087, P= 0.079). However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant

  9. Pre-treatment neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are prognostic of progression in early stage classical Hodgkin lymphoma.

    Science.gov (United States)

    Reddy, Jay P; Hernandez, Mike; Gunther, Jillian R; Dabaja, Bouthaina S; Martin, Geoffrey V; Jiang, Wen; Akhtari, Mani; Allen, Pamela K; Atkinson, Bradley J; Smith, Grace L; Pinnix, Chelsea C; Milgrom, Sarah A; Abou Yehia, Zeinab; Osborne, Eleanor M; Oki, Yasuhiro; Lee, Hun; Hagemeister, Fredrick; Fanale, Michelle A

    2018-02-01

    To determine whether pre-treatment neutrophil/lymphocyte (NLR) or platelet/lymphocyte ratios (PLR) are predictive for progression in early-stage classical Hodgkin lymphoma (cHL), we derived NLR and PLR values for 338 stage I/II cHL patients and appropriate cut-off point values to define progression. Two-year freedom from progression (FFP) for patients with NLR ≥6·4 was 82·2% vs. 95·7% with NLR <6·4 (P < 0·001). Similarly, 2-year FFP was 84·3% for patients with PLR ≥266·2 vs. 96·1% with PLR <266·2 (P = 0·003). On univariate analysis, both NLR and PLR were significantly associated with worse FFP (P = 0·001). On multivariate analysis, PLR remained a significant, independent prognostic factor (P < 0·001). © 2017 John Wiley & Sons Ltd.

  10. Nuclear Cryogenic Propulsion Stage

    Science.gov (United States)

    Houts, Michael G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

    2012-01-01

    The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP.

  11. Prognostic impact of carcinoembryonic antigen and carbohydrate antigen 19-9 in stage IV colorectal cancer patients after R0 resection.