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: Background The purpose of this study was to evaluate the significance of pathologic nodal assessment and extent of nodal metastases on patient outcome in patients with pancreatic adenocarcinoma . Material s and Methods A prospect ively maintained pancreatic cancer data base was review ed , and 696 consecutive patients were identified who underwent resection for pancreatic adenocarcinoma between 1995 and 2005 .  Overall survival was compared to lymph node ( LN ) status , absolute number of pathologically assessed LN , and LN ratio expressed as the number of positive LN to the total LN assessed . Results Of the 696 patients , 598 ( 86 % ) had pancreaticoduodenectomy ( PD ) , and 96 ( 14 % ) had distal pancreatectomy ( DP ) .  For all patients , median follow-up was 13 months ( range , 0–122 months ) , and estimated 5-year survival was 16 % . A total of 243 ( 35 % ) patients were LN-negative ( N0 ) and had a median survival of 27 months . When assessed as a continuous variable , the number of pathologically assessed LN did not correlate with survival for N0 patients undergoing either PD or DP . The median survival for the 453 patients with node-positive ( N1 ) disease was 16 months . When analyzed as a continuous variable , the absolute number of positive LNs was a significant predictor of survival for N1 patients with a linear relationship up to eight positive LNs . LN ratio , as a continuous variable , also predicted survival with a linear relationship up to a ratio of 0.35 . A ratio of 0.18 was associated with a 19-month median survival and served as the best cutoff , p < 0.01 . Conclusions The absolute number of positive LNs and LN ratio are strong predictors of survival for patients with node-positive pancreatic adenocarcinoma . Inadequate surgical lymphadenectomy or pathologic LN assessment understages node-negative patients CONTEXT Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer .  Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer . OBJECTIVE To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer . DESIGN , SETTING , AND PATIENTS The European Study Group for Pancreatic Cancer (ESPAC)-3 trial , an open-label , phase 3 , r and omized controlled trial conducted in 159 pancreatic cancer centers in Europe , Australasia , Japan , and Canada . Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection ; patients were r and omized between July 2000 and January 2007 and underwent at least 2 years of follow-up . INTERVENTIONS Patients received either fluorouracil plus folinic acid ( folinic acid , 20 mg/m(2 ) , intravenous bolus injection , followed by fluorouracil , 425 mg/m(2 ) intravenous bolus injection given 1 - 5 days every 28 days ) ( n = 551 ) or gemcitabine ( 1000 mg/m(2 ) intravenous infusion once a week for 3 of every 4 weeks ) ( n = 537 ) for 6 months . MAIN OUTCOME MEASURES Primary outcome measure was overall survival ; secondary measures were toxicity , progression-free survival , and quality of life . RESULTS Final analysis was carried out on an intention-to-treat basis after a median of 34.2 ( interquartile range , 27.1 - 43.4 ) months ' follow-up after 753 deaths ( 69 % ) . Median survival was 23.0 ( 95 % confidence interval [ CI ] , 21.1 - 25.0 ) months for patients treated with fluorouracil plus folinic acid and 23.6 ( 95 % CI , 21.4 - 26.4 ) months for those treated with gemcitabine ( chi(1)(2 ) = 0.7 ; P = .39 ; hazard ratio , 0.94 [ 95 % CI , 0.81 - 1.08 ] ) . Seventy-seven patients ( 14 % ) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events , compared with 40 patients ( 7.5 % ) receiving gemcitabine , who had 52 events ( P < .001 ) . There were no significant differences in either progression-free survival or global quality -of-life scores between the treatment groups . CONCLUSION Compared with the use of fluorouracil plus folinic acid , gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00058201 Purpose To evaluate the efficacy and safety of the combination of gemcitabine ( GEM ) and S-1 ( GS ) in comparison to GEM alone ( G ) for unresectable pancreatic cancer . Methods In this multicenter r and omized phase II study , we r and omly assigned unresectable pancreatic cancer patients to either the GS group or the G group . The GS group regimen consists of intravenous 1,000 mg/m2 GEM during 30 min on days 1 and 8 , combined with 80 mg/m2 oral S-1 twice daily on days 1–14 , repeated every 3 weeks . On the other h and , the G group regimen consists of intravenous 1,000 mg/m2 GEM on days 1 , 8 , and 15 , repeated every 4 weeks . The primary endpoint was objective response rate ( ORR ) . Secondary end points included treatment toxicity , clinical response benefit , progression-free survival ( PFS ) , and overall survival . Results We registered 117 patients from 16 institutions between June 2007 and August , 2010 . The ORR of the GS group was 28.3 % , whereas that of the G group was 6.8 % . This difference was statistically significant ( P = 0.005 ) . The disease control rate was 64.2 % in the GS group and 44.1 % in the G group . Median PFS was 6.15 months in the GS group and 3.78 month in the G group . This was also statistically significant ( P = 0.0007 ) . Moreover , the median overall survival ( OS ) of the GS group was significantly longer than that of the G group ( 13.7 months vs. 8.0 months ; P = 0.035 ) . The major grade 3–4 adverse events were neutropenia ( 54.7 % in the GS group and 22.0 % in the G group ) , thrombocytopenia ( 15.1 % in the GS group and 5.1 % in the G group ) , and skin rash ( 9.4 % in the GS group ) . Conclusions The GS group showed stronger anticancer activity than the G group , suggesting the need for a large r and omized phase III study to confirm GS advantages in a specific subset INTRODUCTION The aim of the work was to evaluate the implementation of Clavien - Dindo classification of  surgical complications  into a routine clinical praxis and to evaluate the results achieved at the university department of surgery . MATERIAL AND METHODS Prospect ively collected data of patients hospitalized at the Clinic of Surgery of the University Hospital in Hradec Králové between January 2010 and September 2012 were retrospectively evaluated . Incidence , spectrum and severity of postoperative complications were evaluated according to individual surgical specializations . RESULTS 9039 patients were operated and enrolled into the data base during the time period from January 2010 to October 2012 . A surgical complication was recorded in 1248 ( 12.9 % ) patiens , grade I. in 284 ( 3.4 % ) cases , grade II . in 384 ( 4.3 % ) cases , grade III in 370 ( 4.1 % ) cases , grade IV . in 67 ( 0.7 % ) patients . Death , i.e . grade V. , occurred in 143 ( 1.43 % ) patients . CONCLUSION Clavien - Dindo classification of surgical complications was successfully implemented into a routine clinical praxis at the department of surgery , University Hospital Hradec Králové . Wider use of this classification system would improve conditions for evaluation and comparison of results between different surgical approaches , surgeons or departments Pancreatic cancer is a highly aggressive disease with poor survival . The only effective therapy offering long-term survival is complete surgical resection . In the setting of nonmetastatic disease , locally advanced tumors constitute a technical challenge to the surgeon and may result in margin-positive resection margins . Few studies have evaluated the implication s of the latter in depth . The aim of this study was to compare the margin-positive situation to palliative bypass procedures and margin-negative resections in terms of perioperative and long-term outcome . By retrospective analysis of prospect ively maintained data from 360 patients operated for pancreatic cancer at our institution , we provide evidence that margin-positive resection still yields a significant survival benefit over palliative bypass procedures . At the same time , perioperative severe morbidity and mortality are not significantly increased . Our observations suggest that pancreatic cancer should be resected whenever technically feasible , including , cases of locally advanced disease BACKGROUND Axitinib ( AG-013736 ) is a potent and selective oral inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 , which have an important role in pancreatic cancer . The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone . METHODS Between January and August , 2006 , 103 patients with unresectable , locally advanced , or metastatic pancreatic cancer were r and omly assigned in a two to one ratio to receive gemcitabine ( 1000 mg/m(2 ) ) plus axitinib 5 mg twice daily ( n=69 ) or gemcitabine ( 1000 mg/m(2 ) ) alone ( n=34 ) by a central ised registration system . The primary endpoint was overall survival . Analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00219557 . FINDINGS All r and omised patients were included in the efficacy analyses . Median overall survival was longer with gemcitabine plus axitinib than with gemcitabine alone ( 6.9 [ 95 % CI 5.3 - 10.1 ] months vs 5.6 [ 3.9 - 8.8 ] months ) . The hazard ratio for survival with gemcitabine plus axitinib versus with gemcitabine alone , adjusted for stratification factors , was 0.71 ( 95 % CI 0.44 - 1.13 ) . The most common grade 3 or worse adverse events were fatigue ( 15 [ 22 % ] patients in the gemcitabine plus axitinib group vs one [ 3 % ] in the gemcitabine alone group ) , abdominal pain ( eight [ 12 % ] vs five [ 16 % ] ) , and asthenia ( eight [ 12 % ] vs one [ 3 % ] ) . INTERPRETATION Gemcitabine plus axitinib showed a similar safety profile to gemcitabine alone ; the small , non-statistically significant gain in overall survival needs to be assessed in a r and omised phase III trial CONTEXT The role of adjuvant therapy in resectable pancreatic cancer is still uncertain , and no recommended st and ard exists . OBJECTIVE To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more . DESIGN , SETTING , AND PATIENTS Open , multicenter , r and omized controlled phase 3 trial with stratification for resection , tumor , and node status . Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria . A total of 368 patients with gross complete ( R0 or R1 ) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups . INTERVENTION Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1 , 8 , and 15 every 4 weeks ( n = 179 ) , or observation ( [ control ] n = 175 ) . MAIN OUTCOME MEASURES Primary end point was disease-free survival , and secondary end points were overall survival , toxicity , and quality of life . Survival analysis was based on all eligible patients ( intention-to-treat ) . RESULTS More than 80 % of patients had R0 resection . The median number of chemotherapy cycles in the gemcitabine group was 6 ( range , 0 - 6 ) . Grade 3 or 4 toxicities rarely occurred with no difference in quality of life ( by Spitzer index ) between groups . During median follow-up of 53 months , 133 patients ( 74 % ) in the gemcitabine group and 161 patients ( 92 % ) in the control group developed recurrent disease . Median disease-free survival was 13.4 months in the gemcitabine group ( 95 % confidence interval , 11.4 - 15.3 ) and 6.9 months in the control 
    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: Background The purpose of this study was to evaluate the significance of pathologic nodal assessment and extent of nodal metastases on patient outcome in patients with pancreatic adenocarcinoma . Material s and Methods A prospect ively maintained pancreatic cancer data base was review ed , and 696 consecutive patients were identified who underwent resection for pancreatic adenocarcinoma between 1995 and 2005 .  Overall survival was compared to lymph node ( LN ) status , absolute number of pathologically assessed LN , and LN ratio expressed as the number of positive LN to the total LN assessed . Results Of the 696 patients , 598 ( 86 % ) had pancreaticoduodenectomy ( PD ) , and 96 ( 14 % ) had distal pancreatectomy ( DP ) .  For all patients , median follow-up was 13 months ( range , 0–122 months ) , and estimated 5-year survival was 16 % . A total of 243 ( 35 % ) patients were LN-negative ( N0 ) and had a median survival of 27 months . When assessed as a continuous variable , the number of pathologically assessed LN did not correlate with survival for N0 patients undergoing either PD or DP . The median survival for the 453 patients with node-positive ( N1 ) disease was 16 months . When analyzed as a continuous variable , the absolute number of positive LNs was a significant predictor of survival for N1 patients with a linear relationship up to eight positive LNs . LN ratio , as a continuous variable , also predicted survival with a linear relationship up to a ratio of 0.35 . A ratio of 0.18 was associated with a 19-month median survival and served as the best cutoff , p < 0.01 . Conclusions The absolute number of positive LNs and LN ratio are strong predictors of survival for patients with node-positive pancreatic adenocarcinoma . Inadequate surgical lymphadenectomy or pathologic LN assessment understages node-negative patients CONTEXT Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer .  Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer . OBJECTIVE To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer . DESIGN , SETTING , AND PATIENTS The European Study Group for Pancreatic Cancer (ESPAC)-3 trial , an open-label , phase 3 , r and omized controlled trial conducted in 159 pancreatic cancer centers in Europe , Australasia , Japan , and Canada . Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection ; patients were r and omized between July 2000 and January 2007 and underwent at least 2 years of follow-up . INTERVENTIONS Patients received either fluorouracil plus folinic acid ( folinic acid , 20 mg/m(2 ) , intravenous bolus injection , followed by fluorouracil , 425 mg/m(2 ) intravenous bolus injection given 1 - 5 days every 28 days ) ( n = 551 ) or gemcitabine ( 1000 mg/m(2 ) intravenous infusion once a week for 3 of every 4 weeks ) ( n = 537 ) for 6 months . MAIN OUTCOME MEASURES Primary outcome measure was overall survival ; secondary measures were toxicity , progression-free survival , and quality of life . RESULTS Final analysis was carried out on an intention-to-treat basis after a median of 34.2 ( interquartile range , 27.1 - 43.4 ) months ' follow-up after 753 deaths ( 69 % ) . Median survival was 23.0 ( 95 % confidence interval [ CI ] , 21.1 - 25.0 ) months for patients treated with fluorouracil plus folinic acid and 23.6 ( 95 % CI , 21.4 - 26.4 ) months for those treated with gemcitabine ( chi(1)(2 ) = 0.7 ; P = .39 ; hazard ratio , 0.94 [ 95 % CI , 0.81 - 1.08 ] ) . Seventy-seven patients ( 14 % ) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events , compared with 40 patients ( 7.5 % ) receiving gemcitabine , who had 52 events ( P < .001 ) . There were no significant differences in either progression-free survival or global quality -of-life scores between the treatment groups . CONCLUSION Compared with the use of fluorouracil plus folinic acid , gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00058201 Purpose To evaluate the efficacy and safety of the combination of gemcitabine ( GEM ) and S-1 ( GS ) in comparison to GEM alone ( G ) for unresectable pancreatic cancer . Methods In this multicenter r and omized phase II study , we r and omly assigned unresectable pancreatic cancer patients to either the GS group or the G group . The GS group regimen consists of intravenous 1,000 mg/m2 GEM during 30 min on days 1 and 8 , combined with 80 mg/m2 oral S-1 twice daily on days 1–14 , repeated every 3 weeks . On the other h and , the G group regimen consists of intravenous 1,000 mg/m2 GEM on days 1 , 8 , and 15 , repeated every 4 weeks . The primary endpoint was objective response rate ( ORR ) . Secondary end points included treatment toxicity , clinical response benefit , progression-free survival ( PFS ) , and overall survival . Results We registered 117 patients from 16 institutions between June 2007 and August , 2010 . The ORR of the GS group was 28.3 % , whereas that of the G group was 6.8 % . This difference was statistically significant ( P = 0.005 ) . The disease control rate was 64.2 % in the GS group and 44.1 % in the G group . Median PFS was 6.15 months in the GS group and 3.78 month in the G group . This was also statistically significant ( P = 0.0007 ) . Moreover , the median overall survival ( OS ) of the GS group was significantly longer than that of the G group ( 13.7 months vs. 8.0 months ; P = 0.035 ) . The major grade 3–4 adverse events were neutropenia ( 54.7 % in the GS group and 22.0 % in the G group ) , thrombocytopenia ( 15.1 % in the GS group and 5.1 % in the G group ) , and skin rash ( 9.4 % in the GS group ) . Conclusions The GS group showed stronger anticancer activity than the G group , suggesting the need for a large r and omized phase III study to confirm GS advantages in a specific subset INTRODUCTION The aim of the work was to evaluate the implementation of Clavien - Dindo classification of  surgical complications  into a routine clinical praxis and to evaluate the results achieved at the university department of surgery . MATERIAL AND METHODS Prospect ively collected data of patients hospitalized at the Clinic of Surgery of the University Hospital in Hradec Králové between January 2010 and September 2012 were retrospectively evaluated . Incidence , spectrum and severity of postoperative complications were evaluated according to individual surgical specializations . RESULTS 9039 patients were operated and enrolled into the data base during the time period from January 2010 to October 2012 . A surgical complication was recorded in 1248 ( 12.9 % ) patiens , grade I. in 284 ( 3.4 % ) cases , grade II . in 384 ( 4.3 % ) cases , grade III in 370 ( 4.1 % ) cases , grade IV . in 67 ( 0.7 % ) patients . Death , i.e . grade V. , occurred in 143 ( 1.43 % ) patients . CONCLUSION Clavien - Dindo classification of surgical complications was successfully implemented into a routine clinical praxis at the department of surgery , University Hospital Hradec Králové . Wider use of this classification system would improve conditions for evaluation and comparison of results between different surgical approaches , surgeons or departments Pancreatic cancer is a highly aggressive disease with poor survival . The only effective therapy offering long-term survival is complete surgical resection . In the setting of nonmetastatic disease , locally advanced tumors constitute a technical challenge to the surgeon and may result in margin-positive resection margins . Few studies have evaluated the implication s of the latter in depth . The aim of this study was to compare the margin-positive situation to palliative bypass procedures and margin-negative resections in terms of perioperative and long-term outcome . By retrospective analysis of prospect ively maintained data from 360 patients operated for pancreatic cancer at our institution , we provide evidence that margin-positive resection still yields a significant survival benefit over palliative bypass procedures . At the same time , perioperative severe morbidity and mortality are not significantly increased . Our observations suggest that pancreatic cancer should be resected whenever technically feasible , including , cases of locally advanced disease BACKGROUND Axitinib ( AG-013736 ) is a potent and selective oral inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 , which have an important role in pancreatic cancer . The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone . METHODS Between January and August , 2006 , 103 patients with unresectable , locally advanced , or metastatic pancreatic cancer were r and omly assigned in a two to one ratio to receive gemcitabine ( 1000 mg/m(2 ) ) plus axitinib 5 mg twice daily ( n=69 ) or gemcitabine ( 1000 mg/m(2 ) ) alone ( n=34 ) by a central ised registration system . The primary endpoint was overall survival . Analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00219557 . FINDINGS All r and omised patients were included in the efficacy analyses . Median overall survival was longer with gemcitabine plus axitinib than with gemcitabine alone ( 6.9 [ 95 % CI 5.3 - 10.1 ] months vs 5.6 [ 3.9 - 8.8 ] months ) . The hazard ratio for survival with gemcitabine plus axitinib versus with gemcitabine alone , adjusted for stratification factors , was 0.71 ( 95 % CI 0.44 - 1.13 ) . The most common grade 3 or worse adverse events were fatigue ( 15 [ 22 % ] patients in the gemcitabine plus axitinib group vs one [ 3 % ] in the gemcitabine alone group ) , abdominal pain ( eight [ 12 % ] vs five [ 16 % ] ) , and asthenia ( eight [ 12 % ] vs one [ 3 % ] ) . INTERPRETATION Gemcitabine plus axitinib showed a similar safety profile to gemcitabine alone ; the small , non-statistically significant gain in overall survival needs to be assessed in a r and omised phase III trial CONTEXT The role of adjuvant therapy in resectable pancreatic cancer is still uncertain , and no recommended st and ard exists . OBJECTIVE To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more . DESIGN , SETTING , AND PATIENTS Open , multicenter , r and omized controlled phase 3 trial with stratification for resection , tumor , and node status . Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria . A total of 368 patients with gross complete ( R0 or R1 ) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups . INTERVENTION Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1 , 8 , and 15 every 4 weeks ( n = 179 ) , or observation ( [ control ] n = 175 ) . MAIN OUTCOME MEASURES Primary end point was disease-free survival , and secondary end points were overall survival , toxicity , and quality of life . Survival analysis was based on all eligible patients ( intention-to-treat ) . RESULTS More than 80 % of patients had R0 resection . The median number of chemotherapy cycles in the gemcitabine group was 6 ( range , 0 - 6 ) . Grade 3 or 4 toxicities rarely occurred with no difference in quality of life ( by Spitzer index ) between groups . During median follow-up of 53 months , 133 patients ( 74 % ) in the gemcitabine group and 161 patients ( 92 % ) in the control group developed recurrent disease . Median disease-free survival was 13.4 months in the gemcitabine group ( 95 % confidence interval , 11.4 - 15.3 ) and 6.9 months in the control 
    Output:
    