title: The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: McMillan
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. charles.vollmer@uphs.upenn.edu.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Vollmer
authors.affiliation: Department of Surgery, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Horacio J
authors.initials: HJ
authors.lastname: Asbun
authors.affiliation: Department of Surgery, University of Calgary, Calgary, AB, Canada.
authors.forename: Chad G
authors.initials: CG
authors.lastname: Ball
authors.affiliation: Department of Surgery, University of Verona, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bassi
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Joal D
authors.initials: JD
authors.lastname: Beane
authors.affiliation: Department of Surgery, Jefferson Medical College, Philadelphia, PA, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Berger
authors.affiliation: Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Bloomston
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Callery
authors.affiliation: Department of Surgery, University of Alabama, Birmingham, AL, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Christein
authors.affiliation: Department of Surgery, University of Calgary, Calgary, AB, Canada.
authors.forename: Elijah
authors.initials: E
authors.lastname: Dixon
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Drebin
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Carlos Fernandez-Del
authors.initials: CF
authors.lastname: Castillo
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Fisher
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Zhi Ven
authors.initials: ZV
authors.lastname: Fong
authors.affiliation: Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Ericka
authors.initials: E
authors.lastname: Haverick
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: House
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hughes
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Tara S
authors.initials: TS
authors.lastname: Kent
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Kunstman
authors.affiliation: Department of Surgery, University of Verona, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Malleo
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: McElhany
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Salem
authors.affiliation: Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Soares
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Sprys
authors.affiliation: Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Ammara A
authors.initials: AA
authors.lastname: Watkins
authors.affiliation: Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.affiliation: Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Behrman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010185:Pancreatic Fistula / Q000175:diagnosis* / Q000209:etiology*; D016577:Pancreaticoduodenectomy / Q000009:adverse effects*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012086:Reoperation / Q000009:adverse effects; D012307:Risk Factors
keywords: ISGPF grade C; Pancreatic fistula; Risk assessment