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Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use., Objective: To test external validity of the prognostic value of the hidden genome classifier of AA., Design, Setting, and Participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020., Exposures: The multilevel meta-feature regression model previously trained on a prospectively sequenced cohort of 3411 patients (1001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, and 2245 colorectal adenocarcinoma) was applied to AA sequencing data to quantify the relative proportions of parental cell of origin., Main Outcome and Measures: Genomic classification was correlated with immunohistologic subtype (intestinal [INT] or pancreatobiliary [PB]) and with overall survival (OS), using the log-rank test and Cox proportional hazard models., Results: Among 192 patients with AA (median age, 69.0 [IQR, 60.0-74.0] years and 134 were male [64%]), concordance between immunohistologic and genomic subtypes was 55%. Most INT subtype tumors were categorized into the colorectal genomic subtype (43 of 57 [72.9%]). Of the 114 PB subtype tumors, 29 had a pancreatic genomic profile (25.4%) and 24 had a distal bile duct genomic profile (21.1%). Whereas the standard immunohistologic subtypes were not associated with survival (log rank P = .26), predicted genomic probabilities were correlated with survival probability. Genomic scores with higher colorectal probability were associated with higher survival probability; higher pancreatic and distal bile duct probabilities were associated with lower survival probability., Conclusions and Relevance: The AA genomic classifier is reproducible with available molecular testing in a diverse international cohort of patients and improves stratification of the divergent clinical outcomes beyond standard immunohistologic classification. These data provide a molecular classification that may be incorporated into clinical trials for prospective validation.

Objective: To evaluate whether drain fluid amylase levels on day-1 (DFA1) and day-3 (DFA3) can reliably estimate the risk of clinically relevant-postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) compared to either value alone or in combination with clinicopathologic variables., Background: CR-POPF is a major source of morbidity and mortality following PD. Current drain management algorithms are variable and are mostly dependent on DFA1, while the DFA3 is seldom utilized to guide clinical decision making., Methods: Between 2015-2020, patients who underwent PD at two high-volume pancreas centers and had intraoperative drain placement with measurement of DFA1 and DFA3 were retrospectively reviewed. Models to predict CR-POPF were constructed using DFA1, DFA3, fistula risk score (FRS) and other patient or treatment-related parameters. The fittest and more parsimonious model was used to construct a CR-POPF risk calculator., Results: Nine-hundred-twenty-three patients were included in the analysis. The FRS was high in 100(10.9%), intermediate in 524(57.3%), low in 211(23.1%) and negligible in 79(8.6%) patients. The overall rate of CR-POPF was 9.2%. Five logistic regression models were constructed using variables known to be implicated in CR-POPF. A model based solely on DFA1 and DFA3 with a cross-validated area under the curve of 0.846 was selected. A calculator using DFA1 and DFA3 was created based on this model to estimate the risk of CR-POPF., Conclusions: Risk of CR-POPF following pancreatoduodenectomy can be accurately estimated based on measurement of DFA1 and DFA3. Our CR-POPF kinetics calculator can facilitate postoperative risk stratification and guide drain management algorithms., Competing Interests: Disclosures: No conflict of interests to declare, financial or otherwise., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recent studies support early drain removal after pancreaticoduodenectomy in patients with a drain fluid amylase on postoperative day 1 (DFA1) level of ≤5,000. The use of DFA1 to guide drain management is increasingly common among pancreatic surgeons; however, the benefit of checking additional drain fluid amylases beyond DFA1 is less known. We sought to determine whether a change in drain fluid amylase (ΔDFA) is a more reliable predictor of clinically relevant postoperative fistula than DFA1 alone., Methods: Using the American College of Surgeons National Surgical Quality Improvement Plan, pancreaticoduodenectomy patients with intraoperative drain placement, known DFA1, highest recorded drain fluid amylase value on postoperative day 2 to 5 (DFA2nd), day of drain removal, and clinically relevant postoperative fistula status were reviewed. Logistic models compared the predictive performance of DFA1 alone versus DFA1 + ΔDFA., Results: A total of 2,417 patients with an overall clinically relevant postoperative fistula rate of 12.6% were analyzed. On multivariable regression, clinical predictors for clinically relevant postoperative fistula included body mass index, steroid use, operative time, and gland texture. These variables were used to develop model 1 (DFA1 alone) and model 2 (DFA1 + ΔDFA). Model 2 outperformed model 1 in predicting the risk of clinically relevant postoperative fistula. According to model 2 predictions, the risk of clinically relevant postoperative fistula increased with any rise in drain fluid amylase, regardless of whether the DFA1 was above or below 5,000 U/L. The risk of clinically relevant postoperative fistula significantly decreased with any drop in drain fluid amylase, with an odds reduction of approximately 50% corresponding with a 70% decrease in drain fluid amylase (P < .001). A risk calculator was developed using DFA1 and a secondary DFA value in conjunction with other clinical predictors for clinically relevant postoperative fistula., Conclusion: Clinically relevant postoperative fistula after pancreaticoduodenectomy is more accurately predicted by DFA1 and ΔDFA versus DFA1 in isolation. We developed a novel risk calculator to provide an individualized approach to drain management after pancreaticoduodenectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Summary Dr. Paul Greig is an icon of surgical education, transplantation, hepatobiliary surgery and Canadian surgery. Dr. Greig has trained experts in these fields all over the world and is regarded as one of the most important surgical educators in the past 25 years., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

Objective: The aim of this study was to develop a classification system for pancreas-associated risk factors in pancreatoduodenectomy (PD)., Summary Background Data: Postoperative pancreatic fistula (POPF) is the most relevant PD-associated complication. A simple standardized surgical reporting system based on pancreas-associated risk factors is lacking., Methods: A systematic literature search was conducted to identify studies investigating clinically relevant (CR) POPF (CR-POPF) and pancreas-associated risk factors after PD. A meta-analysis of CR-POPF rate for texture of the pancreas (soft vs not-soft) and main pancreatic duct (MPD) diameter was performed using the Mantel-Haenszel method. Based on the results, the International Study Group of Pancreatic Surgery (ISGPS) proposes the following classification: A, not-soft (hard) texture and MPD >3 mm; B, not-soft (hard) texture and MPD ≤3 mm; C, soft texture and MPD >3 mm; D, soft texture and MPD ≤3 mm. The classification was evaluated in a multi-institutional, international cohort., Results: Of the 2917 articles identified, 108 studies were included in the analyses. Soft pancreatic texture was significantly associated with the development of CR-POPF [odds ratio (OR) 4.24, 95% confidence interval (CI) 3.67-4.89, P < 0.01) following PD. Similarly, MPD diameter ≤3 mm significantly increased CR-POPF risk compared with >3 mm diameter MPDs (OR 3.66, 95% CI 2.62-5.12, P < 0.01). The proposed 4-stage system was confirmed in an independent cohort of 5533 patients with CR-POPF rates of 3.5%, 6.2%, 16.6%, and 23.2% for type A-D, respectively ( P < 0.001)., Conclusion: For future pancreatic surgical outcomes studies, the ISGPS recommends reporting these risk factors according to the proposed classification system for better comparability of results., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Patient education and resources that address barriers to health literacy to improve understanding in pancreatic cancer are limited. We evaluated the impact and outcomes benefits of Animated Pancreas Patient (APP) cancer educational modules (APP website and YouTube)., Methods: A retrospective study of APP metrics and utilization data from September 2013 to February 2021 was conducted. We evaluated audience reach and calculated top views by media type (animation/expert video/patient video/slideshow) and top retention videos from the modules., Results: During the study period, APP had 4,551,079 views worldwide of which 2,757,064 unique visitors or 60% were from the United States. Of these, 54% were patients, 17% were family members or caregivers, 16% were health care providers, and 13% were other. The most popular topic viewed among the animations was "Understanding Clinical Trials" (n = 182,217), and the most common expert video viewed was "What are the different stages of pancreatic cancer?" (n = 15,357)., Conclusions: Pancreatic cancer patient education using APP's visual formats of learning demonstrated a wide reach and had a significant impact on improved understanding among patients, families, and caregivers. Continued efforts should be made to provide patient resources that address health literacy, better quality of life and improved health outcomes in pancreatic cancer., Competing Interests: The authors declare no conflict of interest. The Animated Pancreas Patient—An Animated Patient's Guide to Pancreatic Diseases is supported by unrestricted education grants from Abbvie Inc, Boston Scientific Corporation, Celgene Corporation, Ethicon US LLC, and Incyte Corporation. Mechanisms in Medicine, the developers of this resource, declare no conflict of interest in the development of the program., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF., Methods: The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach., Results: A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P < .001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone., Conclusion: In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)