Prognostic Significance of Pathologic Nodal Status in Patients with Resected Pancreatic Cancer Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study) [Classification of surgical complications: analysis of the group of consecutive patients]. Locally Advanced Pancreatic Head Cancer: Margin-Positive Resection or Bypass? Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. Resected adenocarcinoma of the pancreas— 616 patients: Results, outcomes, and prognostic indicators CT criteria for venous invasion in patients with pancreatic head carcinoma. Palliative partial pancreaticoduodenectomy impairs quality of life compared to bypass surgery in patients with advanced adenocarcinoma of the pancreatic head. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. A multi‐institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer Bypass Surgery Versus Palliative Pancreaticoduodenectomy in Patients with Advanced Ductal Adenocarcinoma of the Pancreatic Head, with an Emphasis on Quality of Life Analyses Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma The Need for a Prophylactic Gastrojejunostomy for Unresectable Periampullary Cancer: A Prospective Randomized Multicenter Trial With Special Focus on Assessment of Quality of Life
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 group ( 95 % confidence interval , 6.1 - 7.8 ; P<.001 , log-rank ) . Estimated disease-free survival at 3 and 5 years was 23.5 % and 16.5 % in the gemcitabine group , and 7.5 % and 5.5 % in the control group , respectively . Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection . There was no difference in overall survival between the gemcitabine group ( median , 22.1 months ; 95 % confidence interval , 18.4 - 25.8 ; estimated survival , 34 % at 3 years and 22.5 % at 5 years ) and the control group ( median , 20.2 months ; 95 % confidence interval , 17 - 23.4 ; estimated survival , 20.5 % at 3 years and 11.5 % at 5 years ; P = .06 , log-rank ) . CONCLUSIONS Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone . These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N34802808 This large-volume , single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head , neck , uncinate process , body , or tail of the pancreas . Between January 1984 and July 1999 inclusive , 616 patients with adenocarcinoma of the pancreas underwent surgical resection .  A retrospective analysis of a prospect ively collected data base was performed . Both univariate and multivariate models were used to determine the factors influencing survival . Of the 616 patients , 526 ( 85 % ) underwent pancreaticoduodenectomy for adenocarcinoma of the head , neck , or uncinate process of the pancreas , 52 ( 9 % ) underwent distal pancreatectomy  for adenocarcinoma of the body or tail , and 38 ( 6 % ) underwent total pancreatectomy for adenocarcinoma extensively involving the gl and . The mean age of the patients was 64.3 years , with 54 % being male and 91 % being white . The overall perioperative mortality rate was 2.3 % , whereas the incidence of postoperative complications was 30 % . The median postoperative length of stay was 11 days . The mean tumor diameter was 3.2 cm , with 72 % of patients having positive lymph nodes , 30 % having positive resection margins , and 36 % having poorly differentiated tumors . Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors ( 4.7 vs. 3.1 cm , P < 0.0001 ) , but fewer node-positive resections ( 59 % vs. 73 % , P = 0.03 ) and fewer poorly differentiated tumors ( 29 % vs. 36 % , P<0.001 ) , as compared to those undergoing pancreaticoduodenectomy for right-sided lesions . The overall survival of the entire cohort was 63 % at 1 year and 17 % at 5 years , with a median survival of 17 months . For right-sided lesions the 1- and 5-year survival rates were 64 % and 17 % , respectively , compared to 50 % and 15 % for left-sided lesions . Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins ( hazard ratio [ HR ] = 0.64 , confidence interval [ CI ] = 0.50 to 0.82 , P = 0.0004 ) , tumor diameter less than 3 cm ( HR = 0.72 , CI = 0.57 to 0.90 , P = 0.004 ) , estimated blood loss less than 750 ml ( HR = 0.75 , CI = 0.58 to 0.96 , P = 0.02 ) , well/moderate tumor differentiation ( HR = 0.71 , CI = 0.56 to 0.90 , P = 0.005 ) , and postoperative chemoradiation ( HR = 0.50 , CI = 0.39 to 0.64 , P } < 0.0001 ) . Tumor location in head , neck , or uncinate process approached significance in the final multivariate model ( HR = 0.60 , CI = 0.35 to 1.0 , P = 0.06 ) . Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas . Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators . Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status The purpose of the study was to evaluate CT criteria for venous invasion in patients with potentially resectable carcinoma of the pancreatic head , with surgical and histopathological correlation . In 113 patients evaluated with spiral CT for suspected pancreatic head carcinoma , several CT criteria for venous invasion were scored prospect ively for the portal vein ( PV ) and the superior mesenteric vein ( SMV ) : length of tumour contact with PV/SMV ( 0 mm , < 5 mm , > 5 mm ) ; circumferential involvement of the vein ( 0 degree , 0 - 90 degrees , 90 - 180 degrees , > 180 degrees ) ; degree of stenosis ; irregularity of the vessel margin ; and tumour convexity towards vessel . 65 patients underwent surgery . Pancreatic head carcinoma was proven and pathology of the vascular margin was obtained in 50 of these patients . CT findings for single and combined criteria were correlated with pathology in these 50 patients , 30 of whom showed venous ingrowth . Invasion was found in all cases with SMV narrowing ( n = 7 ) , PV contour involvement > 90 degrees ( n = 6 ) , PV narrowing ( n = 5 ) and PV wall irregularity ( n = 3 ) . The vascular ingrowth rate was 88 % ( 15/17 ) for tumour concavity towards the PV or SMV . Poor predictors of ingrowth were length of tumour contact with PV > 5 mm ( 78 % ingrowth , 14/18 ) and contour involvement of the SMV > 90 degrees ( 83 % ingrowth , 10/12 ) . Absence of vascular ingrowth could not be predicted in 100 % . In conclusion , CT criteria can predict a high risk of invasion in potentially resectable tumours . Narrowing of the SMV and the PV seems the most reliable criterion , as well as circumferential involvement of the PV > 90 degrees . The best combination of criteria was tumour concavity with circumferential involvement > 90 degrees ( sensitivity 60 % and positive predictive value 90 % ) BACKGROUND Some surgical centres consider palliative resection ( PR ) to be superior to double loop bypass ( DLB ) as treatment for advanced carcinoma of the pancreatic head . We performed a retrospective study with prospect ively collected data at a single centre to compare PR and DLB in regard to quality of life ( QoL ) . METHODS From January 1996 to September 2008 , 196 patients were given palliative surgery for advanced pancreatic cancer at the University Hospital of Kiel . Forty-two patients underwent PR and 154 underwent DLB .  These groups were compared with regard to survival , post-operative morbidity , and QoL. The EORTC QLQ-C30 was used to assess QoL before surgery , at discharge , three months after surgery , and six months after surgery . RESULTS The median survival time after PR was 7.5 months ( 95 % CI : 4.95 - 10.05 ) and after DLB was 6 months ( 95 % CI : 4.98 - 7.02 ; log rank test : p = 0.066 ) . There were no significant differences in mortality and morbidity rates ( 7.1 % and 45.2 % for PR ; 3.9 % and 38.3 % for DLB , respectively ) . Assessment of QoL indicated that patients who underwent PR had more impairment of some functional metrics and increased symptoms compared to those who underwent DLB . CONCLUSION There was no significant difference in survival or morbidity after PR and DLB , but patients who underwent DLB had better QoL than patients who underwent PR . Therefore , clinicians may want to reconsider the use of PR for patients with advanced pancreatic cancer BACKGROUND The role of adjuvant treatment in pancreatic cancer remains uncertain . The European Study Group for Pancreatic Cancer ( ESPAC ) assessed the roles of chemoradiotherapy and chemotherapy in a r and omised study . METHODS After resection , patients were r and omly assigned to adjuvant chemoradiotherapy ( 20 Gy in ten daily fractions over 2 weeks with 500 mg/m(2 ) fluorouracil intravenously on days 1 - 3 , repeated after 2 weeks ) or chemotherapy ( intravenous fluorouracil 425 mg/m(2 ) and folinic acid 20 mg/m(2 ) daily for 5 days , monthly for 6 months ) . Clinicians could r and omise patients into a two-by-two factorial design ( observation , chemoradiotherapy alone , chemotherapy alone , or both ) or into one of the main treatment comparisons ( chemoradiotherapy versus no chemoradiotherapy or chemotherapy versus no chemotherapy ) . The primary endpoint was death , and all analyses were by intention to treat . Findings 541 eligible patients with pancreatic ductal adenocarcinoma were r and omised : 285 in the two-by-two factorial design ( 70 chemoradiotherapy , 74 chemotherapy , 72 both , 69 observation ) ; a further 68 patients were r and omly assigned chemoradiotherapy or no chemoradiotherapy and 188 chemotherapy or no chemotherapy .  Median follow-up of the 227 ( 42 % ) patients still alive was 10 months ( range 0 - 62 ) . Overall results showed no benefit for adjuvant chemoradiotherapy ( median survival 15.5 months in 175 patients with chemoradiotherapy vs 16.1 months in 178 patients without ; hazard ratio 1.18 [ 95 % CI 0.90 - 1.55 ] , p=0.24 ) . There was evidence of a survival benefit for adjuvant chemotherapy ( median survival 19.7 months in 238 patients with chemotherapy vs 14.0 months in 235 patients without ; hazard ratio 0.66 [ 0.52 - 0.83 ] , p=0.0005 ) . Interpretation This study showed no survival benefit for adjuvant chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy , justifying further r and omised controlled trials of adjuvant chemotherapy in pancreatic cancer PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms . To date , no treatment has had a significant impact on the disease . In early studies with gemcitabine , patients with pancreas cancer experienced an improvement in disease-related symptoms . Based on those findings , a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer . PATIENTS AND METHODS One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were r and omized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest , then weekly x 3 every 4 weeks thereafter ( 63 patients ) , or to fluorouracil ( 5-FU ) 600 mg/m2 once weekly ( 63 patients ) . The primary efficacy measure was clinical benefit response , which was a composite of measurements of pain ( analgesic consumption and pain intensity ) , Karnofsky performance status , and weight . Clinical benefit required a sustained ( > or = 4 weeks ) improvement in at least one parameter without worsening in any others . Other measures of efficacy included response rate , time to progressive disease , and survival . RESULTS Clinical benefit response was experienced by 23.8 % of gemcitabine-treated patients compared with 4.8 % of 5-FU-treated patients ( P = .0022 ) . The median survival duration s were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients , respectively ( P = .0025 ) . The survival rate at 12 months was 18 % for gemcitabine patients and 2 % for 5-FU patients . Treatment was well tolerated . CONCLUSION This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced , symptomatic pancreas cancer .  Gemcitabine also confers a modest survival advantage over treatment with 5-FU IMPORTANCE The prognosis for patients with pancreatic cancer is poor , even after resection with curative intent . Gemcitabine-based chemotherapy is st and ard treatment for advanced pancreatic cancer , but its effect on survival in the adjuvant setting has not been demonstrated . OBJECTIVE To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival . DESIGN , SETTING , AND PATIENTS CONKO-001 ( Charité Onkologie 001 ) , a multicenter , open-label , phase 3 r and omized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection . Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria . Follow-up ended in September 2012 . INTERVENTIONS After stratification for tumor stage , nodal status , and resection status , patients were r and omly assigned to either adjuvant gemcitabine treatment ( 1g/m2 d 1 , 8 , 15 , q 4 weeks ) for 6 months or to observation alone . MAIN OUTCOMES AND MEASURES The primary end point was disease-free survival . Secondary end points included treatment safety and overall survival , with overall survival defined as the time from date of r and omization to death . Patients lost to follow-up were censored on the date of their last follow-up . RESULTS A total of 368 patients were r and omized , and 354 were eligible for intention-to-treat- analysis . By September 2012 , 308 patients ( 87.0 % [ 95 % CI , 83.1%-90.1 % ] ) had relapsed and 316 patients ( 89.3 % [ 95 % CI , 85.6%-92.1 % ] ) had died . The median follow-up time was 136 months . The median disease-free survival was 13.4 ( 95 % CI , 11.6 - 15.3 ) months in the treatment group compared with 6.7 ( 95 % CI , 6.0 - 7.5 ) months in the observation group ( hazard ratio , 0.55 [ 95 % CI , 0.44 - 0.69 ] ; P < .001 ) . Patients r and omized to adjuvant gemcitabine treatment had prolonged overall survival compared with those r and omized to observation alone ( hazard ratio , 0.76 [ 95 % CI , 0.61 - 0.95 ] ; P = .01 ) , with 5-year overall survival of 20.7 % ( 95 % CI , 14.7%-26.6 % ) vs 10.4 % ( 95 % CI , 5.9%-15.0 % ) , respectively , and 10-year overall survival of 12.2 % ( 95 % CI , 7.3%-17.2 % ) vs 7.7 % ( 95 % CI , 3.6%-11.8 % ) . CONCLUSIONS AND RELEVANCE Among patients with macroscopic complete removal of pancreatic cancer , the use of adjuvant gemcitabine for 6 months compared with observation alone result ed in increased overall survival as well as disease-free survival . These findings provide strong support for the use of gemcitabine in this setting . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N34802808 BACKGROUND The effect of adjuvant treatment on survival in pancreatic cancer is unclear . We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and up date the interim results . METHODS In a multicenter trial using a two-by-two factorial design , we r and omly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone ( 20 Gy over a two-week period plus fluorouracil ) , 75 patients to chemotherapy alone ( fluorouracil ) , 72 patients to both chemoradiotherapy and chemotherapy , and 69 patients to observation .  RESULTS The analysis was based on 237 deaths among the 289 patients ( 82 percent ) and a median follow-up of 47 months ( interquartile range , 33 to 62 ) . The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy ( P=0.05 ) . The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy ( P=0.009 ) . The benefit of chemotherapy persisted after adjustment for major prognostic factors . CONCLUSIONS Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer , whereas adjuvant chemoradiotherapy has a deleterious effect on survival The purpose of this study was to evaluate preoperative treatment with full‐dose gemcitabine , oxaliplatin , and radiation therapy ( RT ) in patients with localized pancreatic cancer Background In some centers , palliative resection ( PR ; partial pancreaticoduodenectomy ) is , in selected cases , promoted in preference to double loop bypass ( DLB ) surgery for advanced pancreatic cancer . This prospect i ve study compares PR with DLB , placing particular focus on patients ’ quality of life ( QoL ) . Methods From 01/1993 to 09/2004 , 167 patients were analyzed in a prospect i ve single center study of palliative surgical treatment of advanced ductal adenocarcinoma of the pancreatic head . Thirty-eight underwent PR and 129 underwent palliative DLB . Patients undergoing DLB  were divided into : ( 1 ) locally advanced disease ( LAD-subgroup ; n = 61 ; 47 % ) and ( 2 ) metastasized disease ( MD-subgroup ; n = 68 ; 53 % ) . QoL was assessed using the EORTC QLQ-C30 question naire supplemented by a pancreatic cancer specific module . QoL data were collected pre-operatively and for up to 12 months after surgery . Results Median survival was 7.0 months ( 95 % CI 4.09 ; 9.91 ) in PR patients and 6.0 months ( 95 % CI 5.39 ; 6.61 ) in patients who received DLB .  Mortality and morbidity were , respectively , 7.8 and 58 % for PR , and 2.6 and 42 % for DLB . QoL decreased more after PR than after DLB . The DLB-group recovered quicker , reaching pre-operative QoL levels after 3 months , and were less impaired when discharged . The LAD-subgroup and the MD-subgroup presented with equal levels of QoL. Conclusions QoL analysis revealed favorable QoL data after DLB . Additionally , the survival rates of the two groups did not differ significantly , but morbidity and mortality rates in the PR group were elevated . Therefore , the use of PR for advanced pancreatic cancer needs to be carefully evaluated Mortality rates associated with pancreatic resection for cancer have steadily decreased with time , but improvements in long‐term survival are less clear . This prospect i ve study evaluated risk factors for survival after resection for pancreatic adenocarcinoma Objective : To evaluate the effect of a prophylactic gastrojejunostomy on the development of gastric outlet obstruction and quality of life in patients with unresectable periampullary cancer found during explorative laparotomy . Summary Background Data : Several studies , including one r and omized trial , propagate to perform a prophylactic gastrojejunostomy routinely in patients with periampullary cancer found to be unresectable during laparotomy . Others suggest an increase of postoperative complications . Controversy still exists in general surgical practice if a double bypass should be performed routinely in these patients . Methods : Between December 1998 and March 2002 , patients with a periampullary carcinoma who were found to be unresectable during exploration were r and omized to receive a double bypass ( hepaticojejunostomy and a retrocolic gastrojejunostomy ) or a single bypass ( hepaticojejunostomy ) . R and omization was stratified for center and presence of metastases . Patients with gastrointestinal obstruction and patients treated endoscopically for more than 3 months were excluded . Primary endpoints were development of clinical gastric outlet obstruction and surgical intervention for gastric outlet obstruction . Secondary endpoints were mortality , morbidity , hospital stay , survival , and quality of life , measured prospect ively by the EORTC-C30 and Pan26 question naires . It was decided to perform an interim analysis after inclusion of 50 % of the patients ( n = 70 ) . Results : Five of the 70 patients r and omized were lost to follow-up . From the remaining 65 patients , 36 patients underwent a double and 29 a single bypass . There were no differences in patient demographics , preoperative symptoms , and surgical findings between the groups . Clinical symptoms of gastric outlet obstruction were found in 2 of the 36 patients ( 5.5 % ) with a double bypass , and in 12 of the 29 patients ( 41.4 % ) with a single bypass ( P = 0.001 ) . In the double bypass group , one patient ( 2.8 % ) and in the single bypass group 6 patients ( 20.7 % ) required (re-)gastrojejunostomy during follow-up ( P = 0.04 ) . The absolute risk reduction for reoperation in the double bypass group was 18 % , and the numbers needed to treat was 6 . Postoperative morbidity rates , including delayed gastric emptying , were 31 % in the double versus 28 % in the single bypass group ( P = 0.12 ) . Median postoperative length of stay was 11 days ( range 4–76 days ) in the double versus 9 days ( range 6–20 days ) in the single bypass group ( P = 0.06 ) ; median survival was 7.2 months in the double versus 8.4 months in the single bypass group ( P = 0.15 ) . No differences were found in the quality of life between both groups . After surgery most quality of life scores deteriorated temporarily and were restored to their baseline score ( t = −1 ) within 4 months . Conclusions : Prophylactic gastrojejunostomy significantly decreases the incidence of gastric outlet obstruction without increasing complication rates . There were no differences in quality of life between the two groups . Together with the previous r and omized trial from the Hopkins group , this study provides sufficient evidence to state that a double bypass consisting of a hepaticojejunostomy and a prophylactic gastrojejunostomy is preferable to a single bypass consisting of only a hepaticojejunostomy in patients undergoing surgical palliation for unresectable periampullary carcinoma . Therefore , the trial was stopped earlier than planned
BACKGROUND Most survival studies comparing non-radical resections to bypass surgery in patients with pancreatic cancer often do not differentiate between an R1 and R2 resection .
The aim of this study was to evaluate whether non-radical R1 and R2 resections have better postoperative outcomes and survival compared to a palliative bypass .