The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy

Matthew T. McMillan, Charles M. Vollmer, Horacio J. Asbun, Chad G. Ball, Claudio Bassi, Joal D. Beane, 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, Ericka Haverick, Michael G. House, Steven J. Hughes, Tara S. Kent, John W. KunstmanGiuseppe Malleo, Amy L. McElhany, Ronald R. Salem, Kevin Soares, Michael H. Sprys, Vicente Valero, Ammara A. Watkins, Christopher L. Wolfgang, Stephen W. Behrman

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57 Scopus citations


Introduction: International Study Group of Pancreatic Fistula (ISGPF) grade C postoperative pancreatic fistulas (POPF) are the greatest contributor to major morbidity and mortality following pancreatoduodenectomy (PD); however, their infrequent occurrence has hindered deeper analysis. This study sought to develop a predictive algorithm, which could facilitate effective management of this challenging complication. Methods: Data were accrued from 4301 PDs worldwide. Demographics, postoperative management, and microbiological characteristics of grade C POPFs were evaluated. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) preoperative and intraoperative variables were compared between grade C POPFs and a 639-case sample of non-grade C POPFs. Risk factors for grade C POPF formation were identified using regression analysis. Results: Grade C POPFs developed in 79 patients (1.8 %). Deaths (90 days) occurred in 2.0 % (N = 88) of the overall series, with 35 % (N = 25) occurring in the presence of a grade C POPF. Reoperations occurred 72.2 % of the time. The rates of single- and multi-system organ failure were 28.2 and 39.7 %, respectively. Mortality rates escalated with pulmonary, renal, and neurologic organ failure, but they were unaffected by reoperation(s). The median number of complications incurred was four (IQR: 2–5), and the median duration of hospital stay was 32 (IQR: 21–54) days. Warning signs for impending grade C POPFs most often presented on postoperative day (POD) 6. Adjuvant chemotherapy might have benefited 55.7 % of grade C POPF patients, yet it was delayed in 25.6 % and never delivered in 67.4 % of these patients. Predictive models for grade C POPF occurrence based on preoperative factors alone and preoperative and intraoperative factors yielded areas under the receiver operating characteristic curve of 0.73 and 0.84 (both P < 0.000001), respectively. Conclusion: This global study represents the largest analysis of grade C POPFs following PD. It describes the severe burden that grade C POPFs incur on patients, with high rates of reoperation and infection, while also potentially worsening overall survival by causing death and delay/omission of adjuvant therapy. Additionally, aggressive clinical management for these POPFs did not improve or worsen 90-day mortality. Predictive tools developed through these data may provide value in managing this difficult complication.

Original languageEnglish (US)
Pages (from-to)262-276
Number of pages15
JournalJournal of Gastrointestinal Surgery
Issue number2
StatePublished - Feb 1 2016


  • ISGPF grade C
  • Pancreatic fistula
  • Risk assessment

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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    McMillan, M. T., Vollmer, C. M., Asbun, H. J., Ball, C. G., Bassi, C., Beane, J. D., Berger, A. C., Bloomston, M., Callery, M. P., Christein, J. D., Dixon, E., Drebin, J. A., Castillo, C. F. D., Fisher, W. E., Fong, Z. V., Haverick, E., House, M. G., Hughes, S. J., Kent, T. S., ... Behrman, S. W. (2016). The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy. Journal of Gastrointestinal Surgery, 20(2), 262-276.