human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers . SUMMARY BACKGROUND DATA A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results . METHODS Eligible patients with T1 - 2N0 - 1aM0 pancreatic head or T1 - 3N0 - 1aM0 periampullary cancer and histologically proven adenocarcinoma were r and omized after resection . RESULTS Between 1987 and 1995 , 218 patients were r and omized ( 108 patients in the observation group , 110 patients in the treatment group ) . Eleven patients were ineligible ( five in the observation group and six in the treatment group ) . Baseline characteristics were comparable between the two groups . One hundred fourteen patients ( 55 % ) had pancreatic cancer ( 54 in the observation group and 60 in the treatment group ) . In the treatment arm , 21 patients ( 20 % ) received no treatment because of postoperative complications or patient refusal . In the treatment group , only minor toxicity was observed . The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group ( log-rank , p = 0.208 ) . The 2-year survival estimates were 41 % and 51 % , respectively . The results when stratifying for tumor location showed a 2-year survival rate of 26 % in the observation group and 34 % in the treatment group ( log-rank , p = 0.099 ) in pancreatic head cancer ; in periampullary cancer , the 2-year survival rate was 63 % in the observation group and 67 % in the treatment group ( log-rank , p = 0.737 ) . No reduction of locoregional recurrence rates was apparent in the groups . CONCLUSIONS Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated . However , the benefit in this study was small ; routine use of adjuvant chemoradiotherapy is not warranted as st and ard treatment in cancer of the head of the pancreas or periampullary region HYPOTHESES Adjuvant chemoradiotherapy decreases the risk of local recurrence in patients with adenocarcinoma of the ampulla of Vater and high-risk features .  Adjuvant chemoradiotherapy for this population can be administered safely and without much morbidity . DESIGN Controlled , prospect i ve , single-arm study . SETTING Tertiary care referral hospital . PATIENTS From June 1995 to March 1999 , 12 patients ( 7 men and 5 women ; median age , 66 years ; age range , 38 - 78 years ) with " unfavorable " ampullary carcinoma were treated with adjuvant chemoradiotherapy .  All patients underwent pancreaticoduodenectomy , and all pathologic findings were confirmed at Stanford University Medical Center , Stanford , Calif. Unfavorable features were defined as involved lymph nodes ( n = 10 ) , involved surgical margins ( n = 1 ) , poorly differentiated histological features ( n = 3 ) , tumor size greater than 2 cm ( n = 6 ) , or the presence of neurovascular invasion ( n = 4 ) . INTERVENTIONS Four to 6 weeks after undergoing pylorus-preserving pancreaticoduodenectomy with regional lymphadenectomy , patients began adjuvant chemoradiotherapy consisting of concurrent radiotherapy ( 45 Gy ) and fluorouracil by protracted venous infusion ( 225 - 250 mg/m(2 ) per day , 7 days per week ) for 5 weeks . MAIN OUTCOME MEASURES Local recurrence , distant recurrence , overall survival rate , and treatment-related toxic effects . RESULTS All patients completed the prescribed treatment course . Toxic effects were assessed twice a week during treatment and grade d according to the National Cancer Institute Common Toxicity Criteria Scale . One patient required a treatment interruption of 1 week for grade III nausea/vomiting . No grade IV or V toxic effects were observed . At median follow-up of 24 months ( range , 13 - 50 months ) , 8 of 12 patients were alive and disease free . One patient was alive but had disease recurrence . Three patients died of this disease ( liver metastases ) . Actuarial overall survival at 2 years was 89 % , and median survival was 34 months . One surviving patient developed a local recurrence and a lung lesion . Actuarial overall survival and median survival were better than in a parallel cohort with resected high-risk pancreatic cancer ( n = 26 ) treated with the same adjuvant chemoradiotherapy regimen ( median survival , 34 vs 14 months ; P<.004 ) . CONCLUSIONS Adjuvant chemoradiotherapy for carcinoma of the ampulla of Vater is well tolerated and might improve control of this disease in patients with unfavorable features Objective The aims of this analysis were to determine prospect ively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma . Background Retrospective analyses have suggested that adjuvant radiation therapy improves survival in patients with perihilar cholangiocarcinoma . However , in these reports , patients receiving radiotherapy  tended to have smaller , often resectable tumors , and were relatively fit . In comparison , patients who have not received radiotherapy  often had unresectable tumors , metastatic disease , or poor performance status . Methods From 1988 through 1993 , surgically staged patients with perihilar cholangiocarcinoma and 1 ) no evidence of metastatic disease , 2 ) Karnofsky score > 60,3 ) no prior malignancy or radiotherapy , and 4 ) a patent main portal vein were analyzed . Fifty patients were stratified by resection ( n = 31 ) versus operative palliation ( n = 19 ) and by radiation ( n = 23 ) versus no radiotherapy ( n = 27 ) . Results Patients undergoing resection had smaller tumors ( 1.9 ± 2.8 vs. 2.4 ± 2.1 cm , p < 0.01 ) that were less likely to invade the hepatic artery ( 3 % vs. 42 % , p < 0.05 ) or portal vein ( 6 % vs. 53 % , p < 0.05 ) . Multiple parameters that might have affected outcome were similar between patients who did and did not receive radiation therapy . Resection improved the length ( 24.2 ± 2.5 vs. 11.3 ± 1.0 months , p < 0.05 ) and quality of survival . Radiation had no effect on the length ( 18.4 ± 2.9 vs. 20.1 ± 2.4 months ) or quality of survival or on late toxicity . Conclusions This analysis suggests that in patients with localized perihilar cholangiocarcinoma , resection prolongs survival  whereas radiation has no effect on either survival or late toxicity . Thus , new agents or strategies to deliver adjuvant therapy are needed to improve survival in these patients HYPOTHESIS This study was design ed to evaluate prospect ively oncological factors determining survival after resection of tumors of the papilla  , comparing local and radical oncological resection . We hypothesized that , in malignant lesions of the ampulla , the T and N stages are major determinants of the patient 's long-term outcome . BACKGROUND DATA The frequency of malignant lesions in adenomas of the papilla is about 26 % . Villous adenoma of the ampulla is considered a premalignant lesion . Local excision has been recommended for benign adenoma and pancreatoduodenectomy for malignant lesions . PATIENTS AND METHODS From January 1 , 1982 , through June 30 , 1997 , 171 patients with tumors of the ampulla of Vater were surgically treated . Demographics , intraoperative factors , tumor pathological findings , and postoperative short- and long-term follow-up data were documented prospect ively . Of the patients , 45 had adenoma of the papilla and 126 had malignant lesions of the ampulla . RESULTS Local resection was performed in 40 of the 45 patients with adenoma . In 98 of the 126 patients with malignant lesions , a radical Kausch-Whipple resection or pylorus-preserving pancreatoduodenectomy was used . Of the patients with benign adenoma , 40 had local resection and 5 had pylorus-preserving pancreatic head resection , with a hospital mortality of 0 % . Thirty of 35 patients had villous adenoma , 9 ( 30 % ) of the 30 with severe dysplasia . Of the 126 patients with malignant lesions , 98 had partial pancreatoduodenectomy and 10 had ampullectomy , with an overall hospital mortality of 3.1 % for patients who underwent resection . Seventy-eight of the 98 patients had an R0 resection . The 5-year survival probability for all patients who underwent resection was 84 % for cancer stage I , 70 % for stage II , and 27 % for stage III . In 8 patients with villous adenoma and carcinoma in situ and in 10 patients with cancer in the adenoma , ampullectomy with local lymph node dissection was performed . In 4 of the patients who had villous adenoma and a carcinoma in stage pT1 N0 , an R0 resection was performed , result ing in cure of cancer . On the basis of a multivariate regression analysis , the prognosis after oncological resection of cancer of the ampulla is determined by the absence of lymph node metastasis ( P<.05 ) , the absence of infiltration into the pancreatic head tissue ( P<.05 ) , and the application of an R0 resection . CONCLUSIONS In patients with villous adenoma of the ampulla , ampullectomy was an adequate surgical treatment . In patients with a low-risk cancer in stages pTis and pT1 N0 M0 , G1 or G2 , a local resection with ampullectomy including local lymph node dissection is justified . An oncological resection of cancer of the ampulla by means of a pylorus-preserving partial pancreatoduodenectomy or the Kausch-Whipple resection is the surgical procedure of choice ; the 3- and 5-year survival rates were 72 % and 52 % , respectively , in patients with R0 resections PURPOSE The benefit of adjuvant radiotherapy ( RT ) for gallbladder cancer remains controversial because most published data are from small , single-institution studies . The purpose of this study was to construct a survival prediction model to enable individualized predictions of the net survival benefit of adjuvant RT for gallbladder cancer patients based on specific tumor and patient characteristics . METHODS A multivariate Cox proportional hazards model was constructed using data from 4,180 patients with resected gallbladder cancer diagnosed from 1988 to 2003 from the Surveillance , Epidemiology , and End Results data base . Patient and tumor characteristics were included as covariates and assessed for association with overall survival ( OS ) with and without adjuvant RT . The model was internally vali date d for discrimination and calibration using bootstrap resampling . RESULTS On multivariate regression analysis , the model showed that age , sex , papillary histology , stage , and adjuvant RT were significant predictors of OS . The survival prediction model demonstrated good calibration and discrimination , with a bootstrap-corrected concordance index of 0.71 . The model predicts that adjuvant RT provides a survival benefit in node-positive or > or= T2 disease . A nomogram and a browser-based software tool were built from the model that can calculate individualized estimates of predicted net survival gain attributable to adjuvant RT , given specific input parameters . CONCLUSION In the absence of large , prospect i ve , r and omized , clinical trial data , a regression model can be used to make individualized predictions of the expected survival improvement from the addition of adjuvant RT after gallbladder cancer resection BACKGROUND In the hierarchy of research design s , the results of r and omized , controlled trials are considered to be evidence of the highest grade , whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects . We used published meta-analyses to identify  r and omized clinical trials and observational studies that examined the same clinical topics . We then compared the results of the original reports according to the type of research design . METHODS A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of r and omized , controlled trials and meta-analyses  of either cohort or case-control studies that assessed the same intervention . For each of five topics , summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual r and omized , controlled trials and the individual observational studies . RESULTS For the five clinical topics and 99 reports evaluated , the average results of the observational studies were remarkably similar to those of the r and omized , controlled trials . For example , analysis of 13 r and omized , controlled trials of the effectiveness of bacille  Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 ( 95 percent confidence interval , 0.34 to 0.70 ) among vaccinated patients , as 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers . SUMMARY BACKGROUND DATA A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results . METHODS Eligible patients with T1 - 2N0 - 1aM0 pancreatic head or T1 - 3N0 - 1aM0 periampullary cancer and histologically proven adenocarcinoma were r and omized after resection . RESULTS Between 1987 and 1995 , 218 patients were r and omized ( 108 patients in the observation group , 110 patients in the treatment group ) . Eleven patients were ineligible ( five in the observation group and six in the treatment group ) . Baseline characteristics were comparable between the two groups . One hundred fourteen patients ( 55 % ) had pancreatic cancer ( 54 in the observation group and 60 in the treatment group ) . In the treatment arm , 21 patients ( 20 % ) received no treatment because of postoperative complications or patient refusal . In the treatment group , only minor toxicity was observed . The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group ( log-rank , p = 0.208 ) . The 2-year survival estimates were 41 % and 51 % , respectively . The results when stratifying for tumor location showed a 2-year survival rate of 26 % in the observation group and 34 % in the treatment group ( log-rank , p = 0.099 ) in pancreatic head cancer ; in periampullary cancer , the 2-year survival rate was 63 % in the observation group and 67 % in the treatment group ( log-rank , p = 0.737 ) . No reduction of locoregional recurrence rates was apparent in the groups . CONCLUSIONS Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated . However , the benefit in this study was small ; routine use of adjuvant chemoradiotherapy is not warranted as st and ard treatment in cancer of the head of the pancreas or periampullary region HYPOTHESES Adjuvant chemoradiotherapy decreases the risk of local recurrence in patients with adenocarcinoma of the ampulla of Vater and high-risk features .  Adjuvant chemoradiotherapy for this population can be administered safely and without much morbidity . DESIGN Controlled , prospect i ve , single-arm study . SETTING Tertiary care referral hospital . PATIENTS From June 1995 to March 1999 , 12 patients ( 7 men and 5 women ; median age , 66 years ; age range , 38 - 78 years ) with " unfavorable " ampullary carcinoma were treated with adjuvant chemoradiotherapy .  All patients underwent pancreaticoduodenectomy , and all pathologic findings were confirmed at Stanford University Medical Center , Stanford , Calif. Unfavorable features were defined as involved lymph nodes ( n = 10 ) , involved surgical margins ( n = 1 ) , poorly differentiated histological features ( n = 3 ) , tumor size greater than 2 cm ( n = 6 ) , or the presence of neurovascular invasion ( n = 4 ) . INTERVENTIONS Four to 6 weeks after undergoing pylorus-preserving pancreaticoduodenectomy with regional lymphadenectomy , patients began adjuvant chemoradiotherapy consisting of concurrent radiotherapy ( 45 Gy ) and fluorouracil by protracted venous infusion ( 225 - 250 mg/m(2 ) per day , 7 days per week ) for 5 weeks . MAIN OUTCOME MEASURES Local recurrence , distant recurrence , overall survival rate , and treatment-related toxic effects . RESULTS All patients completed the prescribed treatment course . Toxic effects were assessed twice a week during treatment and grade d according to the National Cancer Institute Common Toxicity Criteria Scale . One patient required a treatment interruption of 1 week for grade III nausea/vomiting . No grade IV or V toxic effects were observed . At median follow-up of 24 months ( range , 13 - 50 months ) , 8 of 12 patients were alive and disease free . One patient was alive but had disease recurrence . Three patients died of this disease ( liver metastases ) . Actuarial overall survival at 2 years was 89 % , and median survival was 34 months . One surviving patient developed a local recurrence and a lung lesion . Actuarial overall survival and median survival were better than in a parallel cohort with resected high-risk pancreatic cancer ( n = 26 ) treated with the same adjuvant chemoradiotherapy regimen ( median survival , 34 vs 14 months ; P<.004 ) . CONCLUSIONS Adjuvant chemoradiotherapy for carcinoma of the ampulla of Vater is well tolerated and might improve control of this disease in patients with unfavorable features Objective The aims of this analysis were to determine prospect ively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma . Background Retrospective analyses have suggested that adjuvant radiation therapy improves survival in patients with perihilar cholangiocarcinoma . However , in these reports , patients receiving radiotherapy  tended to have smaller , often resectable tumors , and were relatively fit . In comparison , patients who have not received radiotherapy  often had unresectable tumors , metastatic disease , or poor performance status . Methods From 1988 through 1993 , surgically staged patients with perihilar cholangiocarcinoma and 1 ) no evidence of metastatic disease , 2 ) Karnofsky score > 60,3 ) no prior malignancy or radiotherapy , and 4 ) a patent main portal vein were analyzed . Fifty patients were stratified by resection ( n = 31 ) versus operative palliation ( n = 19 ) and by radiation ( n = 23 ) versus no radiotherapy ( n = 27 ) . Results Patients undergoing resection had smaller tumors ( 1.9 ± 2.8 vs. 2.4 ± 2.1 cm , p < 0.01 ) that were less likely to invade the hepatic artery ( 3 % vs. 42 % , p < 0.05 ) or portal vein ( 6 % vs. 53 % , p < 0.05 ) . Multiple parameters that might have affected outcome were similar between patients who did and did not receive radiation therapy . Resection improved the length ( 24.2 ± 2.5 vs. 11.3 ± 1.0 months , p < 0.05 ) and quality of survival . Radiation had no effect on the length ( 18.4 ± 2.9 vs. 20.1 ± 2.4 months ) or quality of survival or on late toxicity . Conclusions This analysis suggests that in patients with localized perihilar cholangiocarcinoma , resection prolongs survival  whereas radiation has no effect on either survival or late toxicity . Thus , new agents or strategies to deliver adjuvant therapy are needed to improve survival in these patients HYPOTHESIS This study was design ed to evaluate prospect ively oncological factors determining survival after resection of tumors of the papilla  , comparing local and radical oncological resection . We hypothesized that , in malignant lesions of the ampulla , the T and N stages are major determinants of the patient 's long-term outcome . BACKGROUND DATA The frequency of malignant lesions in adenomas of the papilla is about 26 % . Villous adenoma of the ampulla is considered a premalignant lesion . Local excision has been recommended for benign adenoma and pancreatoduodenectomy for malignant lesions . PATIENTS AND METHODS From January 1 , 1982 , through June 30 , 1997 , 171 patients with tumors of the ampulla of Vater were surgically treated . Demographics , intraoperative factors , tumor pathological findings , and postoperative short- and long-term follow-up data were documented prospect ively . Of the patients , 45 had adenoma of the papilla and 126 had malignant lesions of the ampulla . RESULTS Local resection was performed in 40 of the 45 patients with adenoma . In 98 of the 126 patients with malignant lesions , a radical Kausch-Whipple resection or pylorus-preserving pancreatoduodenectomy was used . Of the patients with benign adenoma , 40 had local resection and 5 had pylorus-preserving pancreatic head resection , with a hospital mortality of 0 % . Thirty of 35 patients had villous adenoma , 9 ( 30 % ) of the 30 with severe dysplasia . Of the 126 patients with malignant lesions , 98 had partial pancreatoduodenectomy and 10 had ampullectomy , with an overall hospital mortality of 3.1 % for patients who underwent resection . Seventy-eight of the 98 patients had an R0 resection . The 5-year survival probability for all patients who underwent resection was 84 % for cancer stage I , 70 % for stage II , and 27 % for stage III . In 8 patients with villous adenoma and carcinoma in situ and in 10 patients with cancer in the adenoma , ampullectomy with local lymph node dissection was performed . In 4 of the patients who had villous adenoma and a carcinoma in stage pT1 N0 , an R0 resection was performed , result ing in cure of cancer . On the basis of a multivariate regression analysis , the prognosis after oncological resection of cancer of the ampulla is determined by the absence of lymph node metastasis ( P<.05 ) , the absence of infiltration into the pancreatic head tissue ( P<.05 ) , and the application of an R0 resection . CONCLUSIONS In patients with villous adenoma of the ampulla , ampullectomy was an adequate surgical treatment . In patients with a low-risk cancer in stages pTis and pT1 N0 M0 , G1 or G2 , a local resection with ampullectomy including local lymph node dissection is justified . An oncological resection of cancer of the ampulla by means of a pylorus-preserving partial pancreatoduodenectomy or the Kausch-Whipple resection is the surgical procedure of choice ; the 3- and 5-year survival rates were 72 % and 52 % , respectively , in patients with R0 resections PURPOSE The benefit of adjuvant radiotherapy ( RT ) for gallbladder cancer remains controversial because most published data are from small , single-institution studies . The purpose of this study was to construct a survival prediction model to enable individualized predictions of the net survival benefit of adjuvant RT for gallbladder cancer patients based on specific tumor and patient characteristics . METHODS A multivariate Cox proportional hazards model was constructed using data from 4,180 patients with resected gallbladder cancer diagnosed from 1988 to 2003 from the Surveillance , Epidemiology , and End Results data base . Patient and tumor characteristics were included as covariates and assessed for association with overall survival ( OS ) with and without adjuvant RT . The model was internally vali date d for discrimination and calibration using bootstrap resampling . RESULTS On multivariate regression analysis , the model showed that age , sex , papillary histology , stage , and adjuvant RT were significant predictors of OS . The survival prediction model demonstrated good calibration and discrimination , with a bootstrap-corrected concordance index of 0.71 . The model predicts that adjuvant RT provides a survival benefit in node-positive or > or= T2 disease . A nomogram and a browser-based software tool were built from the model that can calculate individualized estimates of predicted net survival gain attributable to adjuvant RT , given specific input parameters . CONCLUSION In the absence of large , prospect i ve , r and omized , clinical trial data , a regression model can be used to make individualized predictions of the expected survival improvement from the addition of adjuvant RT after gallbladder cancer resection BACKGROUND In the hierarchy of research design s , the results of r and omized , controlled trials are considered to be evidence of the highest grade , whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects . We used published meta-analyses to identify  r and omized clinical trials and observational studies that examined the same clinical topics . We then compared the results of the original reports according to the type of research design . METHODS A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of r and omized , controlled trials and meta-analyses  of either cohort or case-control studies that assessed the same intervention . For each of five topics , summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual r and omized , controlled trials and the individual observational studies . RESULTS For the five clinical topics and 99 reports evaluated , the average results of the observational studies were remarkably similar to those of the r and omized , controlled trials . For example , analysis of 13 r and omized , controlled trials of the effectiveness of bacille  Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 ( 95 percent confidence interval , 0.34 to 0.70 ) among vaccinated patients , as 
    Output:
    