Importance: In the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic fistula and related overall survival (OS) in this setting are limited. Objective: To compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS. Design, Setting, and Participants: This retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017. Exposures: Pancreatic cancer surgery with or without NAT. Main Outcomes and Measures: Overall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model. Results: Of 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean [SD], 26.0 [15.3] mm vs 32.7 [14.4] mm; P < .001), reduced nodal involvement (102 [25.1%] vs 191 [55.2%]; P < .001), and higher R0 rates (257 [74.3%] vs 239 [58.7%]; P < .001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 [3.8%] vs 56 [13.8%]; P < .001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P < .001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P = .66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P = .002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P < .002). Conclusions and Relevance: Neoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.
Importance: In the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic fistula and related overall survival (OS) in this setting are limited. Objective: To compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS. Design, Setting, and Participants: This retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017. Exposures: Pancreatic cancer surgery with or without NAT. Main Outcomes and Measures: Overall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model. Results: Of 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean [SD], 26.0 [15.3] mm vs 32.7 [14.4] mm; P < .001), reduced nodal involvement (102 [25.1%] vs 191 [55.2%]; P < .001), and higher R0 rates (257 [74.3%] vs 239 [58.7%]; P < .001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 [3.8%] vs 56 [13.8%]; P < .001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P < .001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P = .66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P = .002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P < .002). Conclusions and Relevance: Neoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.
Authors: Zhi Ven Fong; Donna Marie L Alvino; Carlos Fernández-Del Castillo; Winta T Mehtsun; Ilaria Pergolini; Andrew L Warshaw; David C Chang; Keith D Lillemoe; Cristina R Ferrone Journal: Ann Surg Oncol Date: 2017-07-17 Impact factor: 5.344
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Authors: Matthew T McMillan; Sameer Soi; Horacio J Asbun; Chad G Ball; Claudio Bassi; Joal D Beane; Stephen W Behrman; Adam C Berger; Mark Bloomston; Mark P Callery; John D Christein; Elijah Dixon; Jeffrey A Drebin; Carlos Fernandez-Del Castillo; William E Fisher; Zhi Ven Fong; Michael G House; Steven J Hughes; Tara S Kent; John W Kunstman; Giuseppe Malleo; Benjamin C Miller; Ronald R Salem; Kevin Soares; Vicente Valero; Christopher L Wolfgang; Charles M Vollmer Journal: Ann Surg Date: 2016-08 Impact factor: 12.969
Authors: Theodoros Michelakos; Ilaria Pergolini; Carlos Fernández-Del Castillo; Kim C Honselmann; Lei Cai; Vikram Deshpande; Jennifer Y Wo; David P Ryan; Jill N Allen; Lawrence S Blaszkowsky; Jeffrey W Clark; Janet E Murphy; Ryan D Nipp; Aparna Parikh; Motaz Qadan; Andrew L Warshaw; Theodore S Hong; Keith D Lillemoe; Cristina R Ferrone Journal: Ann Surg Date: 2019-04 Impact factor: 12.969
Authors: John P Neoptolemos; Daniel H Palmer; Paula Ghaneh; Eftychia E Psarelli; Juan W Valle; Christopher M Halloran; Olusola Faluyi; Derek A O'Reilly; David Cunningham; Jonathan Wadsley; Suzanne Darby; Tim Meyer; Roopinder Gillmore; Alan Anthoney; Pehr Lind; Bengt Glimelius; Stephen Falk; Jakob R Izbicki; Gary William Middleton; Sebastian Cummins; Paul J Ross; Harpreet Wasan; Alec McDonald; Tom Crosby; Yuk Ting Ma; Kinnari Patel; David Sherriff; Rubin Soomal; David Borg; Sharmila Sothi; Pascal Hammel; Thilo Hackert; Richard Jackson; Markus W Büchler Journal: Lancet Date: 2017-01-25 Impact factor: 79.321
Authors: Alessandro Paniccia; Ana L Gleisner; Mazen S Zenati; Amr I Al Abbas; Jae Pil Jung; Nathan Bahary; Kenneth K W Lee; David Bartlett; Melissa E Hogg; Herbert J Zeh; Amer H Zureikat Journal: Ann Surg Oncol Date: 2020-03-28 Impact factor: 5.344