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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.)

Background: Despite abundant, high-level scientific evidence, there is no consensus regarding the prevention, mitigation, and management of clinically relevant pancreatic fistula after pancreatoduodenectomy. The aim of the present investigation is three-fold: (1) to analyze the multiple decision-making points for pancreatico-enteric anastomotic creation and fistula mitigation and management after pancreatoduodenectomy, (2) to reveal the practice of contemporary experts, and (3) to indicate avenues for future research to reduce the burden of clinically relevant pancreatic fistula., Methods: A 109-item questionnaire was sent to a panel of international pancreatic surgery experts, recognized for their clinical and scientific authority. Their practice habits and thought processes regarding clinically relevant pancreatic fistula risk assessment, anastomotic construction, application of technical adjuncts, and mitigation strategies, as well as postoperative management, was explored. Sixteen clinical vignettes were presented to reveal their certain approaches to unique situations-both common and uncommon., Results: Sixty experts, with a cumulative 48,860 pancreatoduodenectomies, completed the questionnaire. Their median pancreatectomy/pancreatoduodenectomy case volume was 1,200 and 705 procedures, respectively, with a median career duration of 22 years and 200 indexed publications. Although pancreatico-jejunostomy reconstruction with transperitoneal drainage is the standard operative approach for most authorities, uncertainty emerges regarding the employment of objective risk stratification and adaptation of practice to risk. Concrete suggestions are offered to inform decision-making in intimidating circumstances. Early drain removal is frequently embraced, while a step-up approach is unanimously invoked to treat severe clinically relevant pancreatic fistula., Conclusion: A comprehensive conceptual framework of 4 sequential phases of decision-making is proposed-risk assessment, anastomotic technique, mitigation strategy employment, and postoperative management. Basic science studies and outcome analyses are proposed for improvement., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to characterize an international cohort of resected cystic pancreatic neuroendocrine neoplasms (cPanNENs) and identify preoperative predictors of aggressive behavior., Background: The characteristics of cPanNENs are unknown and their clinical management remains unclear. An observational strategy for asymptomatic cPanNENs ≤2 cm has been proposed by recent guidelines, but evidence is scarce and limited to single-institutional series., Methods: Resected cPanNENs (1995-2017) from 16 institutions worldwide were included. Solid lesions (>50% solid component), functional tumors, and MEN-1 patients were excluded. Aggressiveness was defined as lymph node (LN) involvement, G3 grading, distant metastases, and/or recurrence., Results: Overall, 263 resected cPanNENs were included, among which 177 (63.5%) were >2 cm preoperatively. A preoperative diagnosis of cPanNEN was established in 162 cases (61.6%) and was more frequent when patients underwent endoscopic ultrasound [EUS, odds ratio (OR) 2.69, 95% confidence interval (CI) 1.52-4.77] and somatostatin-receptor imaging (OR 3.681, 95% CI 1.809-7.490), and for those managed in specialized institutions (OR 3.12, 95% CI 1.57-6.21). Forty-one cPanNENs (15.6%) were considered aggressive. In the whole cohort, LN involvement on imaging, age >65 years, preoperative size >2 cm, and pancreatic duct dilation were independently associated with aggressive behavior. In asymptomatic patients, older age and a preoperative size >2 cm remained independently associated with aggressiveness. Only 1 of 61 asymptomatic cPanNENs ≤2 cm displayed an aggressive behavior., Conclusions: The diagnostic accuracy of cPanNENs is increased by the use of EUS and somatostatin-receptor imaging and is higher in specialized institutions. Preoperative size >2 cm is independently associated with aggressive behavior. Consequently, a watch-and-wait policy for sporadic asymptomatic cPanNENs ≤2 cm seems justified and safe for most patients., Competing Interests: This work was performed and written as part of a project of the 8th Pancreas 2000 program funded and organized by the European Pancreatic Club (EPC). None of the authors have any financial or any other kind of personal conflicts of interest in relation to this study The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood., Methods: The fistula risk score was applied to identify high-risk patients (fistula risk score 7-10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003-2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models., Results: Eight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (-49.7%) and career length (-41.2%; both P < .001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35-0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22-0.74)., Conclusion: Surgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no conflicts of interests to disclose.

Pancreatic fistula has been the defining complication and challenge of pancreatic surgery. Better awareness and mitigation of postoperative pancreatic fistulas has led to significant improvements in morbidity and mortality of pancreatic surgery. The definition and management of pancreatic fistulas has sequentially progressed over the last three decades; the literature ranges from retrospective, observational studies to prospective multicenter randomized controlled trials. The landmark literature contributions driving the perioperative management of pancreatic fistulas are detailed in this article.

Background: Health care expenditure is increasing around the world and surgery is a major cause of financial hardship to patients and their families. Using pancreatoduodenectomy (PD), one of the most complex, morbid and costly operation as an example, this study aimed to identify the cost drivers of surgery, estimate relative contribution of these drivers, and derive and validate a cohort-specific cost forecasting tool., Methods: Data on the costs of 1406 patients undergoing PD in three tertiary hospitals in India, Italy and the United States were analysed. Cost drivers were identified and cost models developed using a 4-stage process., Results: There was a significant difference in overall cost of PD between the 3 cohorts. The cost drivers common to the 3 cohorts included duration of hospital stay and the outcome of death (Clavien-Dindo 5). Significant cohort-specific cost drivers included co-morbidities, operating theatre utilisation times and operative blood loss, development of pancreatectomy-specific complications (POPF, DGE, PPH), and need for interventional radiology to manage complications. Based on this, a cost forecasting tool was developed., Conclusions: Drivers of costs for a surgical procedure (e.g. PD) are different between hospitals. Developing cost models/nomograms to predict the expected cost of surgery and perioperative care will not be applicable between hospitals. However, the approach could be used to develop context-specific data that will provide patients (at the time of the informed financial consent) and funding agencies with a more realistic cost estimate for a given operation. The developed cost forecasting tool warrants future validation., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Periampullary malignancies are often unresectable tumors that frequently cause biliary or duodenal obstruction. Advances in endoscopic and percutaneous options have lessened the need for operative palliation. Nevertheless, many patients are still found to be unresectable at the time of exploration, making palliative bypass a consideration. Several prior studies have examined the morbidity of operative palliation, but many were conducted over lengthy time periods, and few have examined the impact of these procedures on future therapy. This study is a contemporary analysis of the short- and long-term outcomes of palliative bypass procedures for unresectable periampullary malignancies at a single high-volume institution., Methods: We identified a contemporary cohort of patients in whom a pancreatoduodenectomy was planned for periampullary malignancy but instead underwent an aborted procedure. Patients were divided into 5 procedure groups: laparoscopy only, laparotomy with or without cholecystectomy, gastrointestinal bypass, biliary bypass, and double bypass (gastrointestinal and biliary). Data regarding the patient cohort, procedures, morbidity/mortality, and the interval to initiation of systemic therapy were collected prospectively and reviewed retrospectively., Results: Between July 2011 and November 2018, 128 out of 615 (17%) patients had an aborted pancreatoduodenectomy; 113 out of 128 patients had pancreatic adenocarcinoma, and 86 (67.1%) had duodenal or biliary obstruction at the time of operation. Patients who underwent laparoscopy only (n = 34) had no operative complications and a 90-day mortality of 6%; 88% of these patients went on to receive systemic therapy (median 21 days postprocedure). Double bypass was associated with a far lesser complication rate than in prior studies; 17% of patients had some complication(s), but only 9% had a severe complication. The 90-day all-cause mortality was 13%, and only 71% of these patients went on to receive systemic therapy (median 47 days postprocedure). Notably, 27 out of 34 (79%) of patients who underwent laparoscopy alone needed additional procedures for local obstruction, whereas only 5 out of 42 (12%) double bypass patients needed additional interventions. Median survival for the entire cohort was 10.3 months., Conclusion: Palliative procedures in this cohort had a far lesser complication rate than that of historical series. Palliative procedures, however, delayed systemic therapy, and a fair number of patients never received additional treatments. Palliative procedures markedly decreased the need for future interventions. Intraoperative decisions regarding palliative procedures must incorporate the functional status and motivations of the patient; these procedures are increasingly safe but may still affect survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To explore contemporary drain management practices and examine the impact of early removal following distal pancreatectomy (DP)., Background: Despite accruing evidence supporting its benefit following pancreatoduodenectomy, early drain removal after DP has yet to be explored., Methods: The American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) was queried for elective DPs from 2014 to 2017. When possible, data were linked to survey responses regarding drain management from hepato-pancreato-biliary (HPB) surgeons in the ACS-NSQIP HPB Collaborative conducted in 2017. The independent association between timing of drain removal and patients' outcomes was investigated through multivariable analyses and propensity-score matching., Results: Of 5581 DPs identified, 4708 (84.4%) patients received intraoperative drains and early removal (≤ POD3) was performed in 716 (15.2%). Drain fluid amylase was recorded on POD1 for 1285 (27.3%) patients who received drains. The overall rates of death or serious morbidity (DSM) and clinically-relevant fistula (CR-POPF) were 19.5% and 17.0%. Early removal demonstrated significantly better outcomes when compared to late removal and no drain placement for: DSM, CR-POPF, delayed gastric emptying, percutaneous drainage, length of stay, and readmission. On multivariable analysis, early removal demonstrated reduced odds of developing DSM (OR = 0.41, 95% CI = 0.26-0.65) and CR-POPF (OR = 0.33, 95% CI = 0.18-0.61) compared to no drain placement, while late removal displayed increased odds for CR-POPF (OR = 2.15, 95% CI = 1.27-3.61) when compared to no drain placement. After propensity-score matching, early removal was associated with reduced odds for CR-POPF (OR = 0.35, 95% CI = 0.17-0.73)., Conclusion: Although not yet widely implemented, early drain removal after distal pancreatectomy is associated with better outcomes. This study demonstrates the potential benefits of early removal and provides a substrate to define best practices and improve the quality of care for DP.

Background: Weight change offers the simplest indication of a patient's recovery after an operation. There have been no studies that have thoroughly investigated postoperative weight dynamics after pancreatectomy. The aim of this study was to define postoperative weight change after a pancreatectomy and determine factors associated with optimal and poor weight trajectories., Methods: From 2004 to 2019, 1,090 proximal (65%) and distal (35%) pancreatectomies were performed in patients with adequate data in the medical records. Patient weights were acquired preoperatively and at postoperative months 1, 3, and 12. Optimal (top quartile, weight restoration) and poor (bottom quartile, persistent weight loss) postoperative weight cohorts were identified at 1 year postoperatively., Results: The median percentage weight change 1 year postpancreatectomy was -6.6% (interquartile range: -1.4% to -12.5%), -7.8% for proximal pancreatectomy, and -4.2% for distal pancreatectomy. For most patients (interquartile range cohort), the median percentage weight change at 1, 3, and 12 months was -6.2%, -7.2%, and -6.6%. The independent factors associated with weight restoration were age <65, nonobesity (body mass index <30kg/m 2 ), receiving total parenteral nutrition/total enteral nutrition preoperatively, experiencing preoperative weight loss >10%, distal pancreatectomy, not undergoing vascular resection, and no readmission within 30 days. Conversely, persistent weight loss was associated with American Society of Anesthesiologists classes III to IV, obesity, malignancy, proximal pancreatectomy, blood loss ≥350mL, and experiencing readmission within 30 days. Focusing on pancreatic ductal adenocarcinoma (n = 372) patients, the factors associated with persistent weight loss were obesity, proximal pancreatectomy, and experiencing recurrence within 1 year; however, weight cohorts were not associated with overall survival for pancreatic ductal adenocarcinoma patients., Conclusion: These data define weight kinetics after pancreatectomy. Ultimately, postoperative weight trajectories appear to be largely predetermined but may be mitigated by limiting readmissions and complications. Clinicians should use these data to identify patients who continue to lose weight between the first and third month postoperatively with a high suspicion for the requirement of nutritional monitoring or other interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Patients who have had splenectomy have a lifelong risk of overwhelming postsplenectomy infection (OPSI), a condition associated with high mortality rates. Surgeons must be aware of the rationale of vaccination in the case of splenectomy, to provide appropriate immunization in the perioperative time., Observations: English-language articles published from January 1, 1990, to December 31, 2019, were retrieved from MEDLINE/PubMed, Cochrane Library, and ClinicalTrials.gov databases. Randomized clinical trials as well as systematic reviews and observational studies were considered. Asplenia yields an impairment of both innate and adaptive immunity, thus increasing the risk of severe encapsulated bacterial infections. Current epidemiology of OPSI ranges from 0.1% to 8.5% but is hard to ascertain because of ongoing shifts in patients' baseline conditions and vaccine penetration. Despite the lack of randomized clinical trials, immunization appears to be effective in reducing OPSI incidence. Unfortunately, vaccination coverage is still suboptimal, with a great variability in vaccination rates being reported across institutions and time frames. Notably, current guidelines do not advocate any particular health care qualification responsible for vaccine prescription or administration. Given the dearth of high-level basic science or clinical evidence, the optimal vaccination timing and the need for booster doses are not yet well established. Although almost all guidelines indicate to not administer vaccines within 14 days before and after surgery, most data suggest that immunization might be effective even in the immediate perioperative time, thus placing the surgeon in a primary position for vaccine delivery. Furthermore, revaccination schedules are the target of ongoing debates, since a vaccine-driven hyporesponsiveness has been postulated., Conclusions and Relevance: In patients who have undergone splenectomy, OPSI might be effectively prevented by proper immunization. Surgeons have the primary responsibility for achieving adequate, initial immunization in the setting of both planned and urgent splenectomy.

Background: The aim was to evaluate the various operative techniques and outcomes used to manage the pancreatic transection plane (or stump) during a left (distal) pancreatectomy and to develop expert consensus guidelines., Methods: Evidence-based, clinically relevant questions were discussed and then were circulated among members of the International Study Group of Pancreatic Surgery. After agreement on the questions and statements, voting in a 9-point Likert scale was used to gauge the level of objective support for each., Results: Studies using the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula including 16 randomized trials were reviewed to generate a series of statements set into 14 domains. There was strong consensus in the following statements: there was no difference in the postoperative pancreatic fistula rate after left pancreatectomy between the handsewn and stapler techniques; a stapling technique could not be used in all cases of left pancreatectomy; the use of an energy-based tissue sealant or a chemical sealant device or combinations of these did not impact the postoperative pancreatic fistula rate; there was no difference in the postoperative pancreatic fistula rate between the open, laparoscopic, or robotic approaches; and there are 1 or more clinically important, patient-related risk factors associated with the postoperative pancreatic fistula rate. There was weak or conditional agreement on the use of prophylactic somatostatin analogs, stents, stump closure, stump anastomosis, and the role of abdominal drains., Conclusion: Areas of strong consensus suggests a change in clinical practice and priority setting. Eight domains with lower agreement will require novel approaches and large multicenter studies to determine future key areas of practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Since 2012, the AHPBA has hosted an annual HPB Fellows' Course at Carolinas Medical Center. All fellows training in an accredited HPB fellowship are eligible to attend. The aim of this study was to evaluate the impact of this conference and assess possible areas of improvement., Methods: The Carolinas Fellows' Course (CFC) is a structured educational activity involving didactics, skills labs, and live case presentations. The course emphasizes minimally invasive surgery (MIS) and intraoperative ultrasound (IOUS) technique. This is a retrospective review of a survey emailed to 95 fellows who have attended the course over a 7-year period., Results: Fifty-two attendees completed the survey (54.7% response rate). Sixty-eight percent of respondents now practice primarily HPB surgery. Seventy-six percent agreed that the CFC encouraged them to incorporate IOUS into their practice, while 74% were encouraged to incorporate MIS HPB procedures into their practice. Eighty percent felt that the course laid groundwork for long term communication with peers., Conclusion: The study demonstrates that a multisite instructional course can be an effective way to encourage the development of new skills, boost operational confidence, impact real world practices, and foster long term communication and networking among fellows after graduation., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Hyperbilirubinemia is commonly observed in patients requiring pancreatoduodenectomy (PD). Thus far, literature regarding the danger of operating in the setting of hyperbilirubinemia is equivocal. What remains undefined is at what specific level of bilirubin there is an adverse safety profile for undergoing PD. The aim of this study is to identify the optimal safety profile of patients with hyperbilirubinemia undergoing PD., Patients and Methods: The present work analyzed 803 PDs from 2004 to 2018. A generalized additive model was used to determine cutoff values of total serum bilirubin (TB) that were associated with increases in adverse outcomes, including 90-day mortality. Subgroup comparisons and biliary stent-specific analyses were performed for patients with TB below and above the cutoff., Results: TB of 13 mg/dL was associated with an increase in 90-day mortality (P = 0.043) and was the dominant risk factor on multivariate logistic regression [odds ratio (OR) 8.193, P = 0.001]. Increased TB levels were also associated with reoperations, number of complications per patient, and length of stay. Patients with TB greater than or equal to 13 mg/dL (TB ≥ 13) who received successful biliary decompression through stenting had less combined death and serious morbidity (P = 0.048)., Conclusions: Preoperative TB ≥ 13 mg/dL was associated with increased 90-day mortality after PD. Reducing a TB ≥ 13 is generally recommended before proceeding to surgery.

Background: Intraoperative drain use for pancreaticoduodenectomy has been practiced in an unconditional, binary manner (placement/no placement). Alternatively, dynamic drain management has been introduced, incorporating the Fistula Risk Score (FRS) and drain fluid amylase (DFA) analysis, to mitigate clinically relevant postoperative pancreatic fistula (CR-POPF)., Study Design: An extended experience with dynamic drain management was used at a single institution for 400 consecutive pancreaticoduodenectomies (2014 to 2019). This protocol consists of the following: drains omitted for negligible/low-risk FRS (0 to 2) and drains placed for moderate/high-risk FRS (3 to 10) with early (postoperative day [POD] 3) removal if POD1 DFA ≤5,000 U/L. Adherence to this protocol was prospectively annotated and outcomes were retrospectively analyzed., Results: The overall CR-POPF rate was 8.7%, with none occurring in the negligible/low-risk cases. Moderate/high-risk patients manifested an 11.9% CR-POPF rate (n = 35 of 293), which was lower on-protocol (9.5% vs 21%; p = 0.014). After drain placement, POD1 DFA ≥5,000 U/L was a better predictor of CR-POPF than FRS (odds ratio 14.7; 95% CI, 4.3 to 50.3). For POD1 DFA ≤5,000 U/L, early drain removal was associated with fewer CR-POPFs (2.8% vs 23.5%; p < 0.001), and substantiated by multivariable analysis (odds ratio 0.09; 95% CI, 0.03 to 0.28). Surgeon adherence was inversely related to CR-POPF rate (R = 0.846)., Conclusions: This extended experience validates a dynamic drain management protocol, providing a model for better drain management and individualized patient care after pancreaticoduodenectomy. This study confirms that drains can be safely omitted from negligible/low-risk patients, and moderate/high-risk patients benefit from early drain removal., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The association between higher surgical volume and better perioperative outcomes after pancreatectomy has been extensively demonstrated. However, how different notions of experience impact outcomes of surgeons operating within high-quality scenarios remains unclear., Methods: Self-reported experience parameters from ACS-NSQIP HPB-Collaborative surgeons were merged with 2014-2016 ACS-NSQIP clinical data. The association of various experience parameters with outcomes was investigated through uni- and multivariable analyses. Hierarchical regression assessed surgeon performance., Results: 111/151 HPB-Collaborative surgeons provided responses (73.5%). Compared to the other 532 ACS-NSQIP surgeons performing pancreatectomy, HPB-Collaborative surgeons performed 7692/16,239 of the overall pancreatectomies (47.3%), with improved outcomes of serious morbidity, pancreatic fistula, reoperation, duration of stay and readmissions. Median age of respondents was 49 years and 92.8% were fellowship-trained. Median career and annual pancreatectomy volume were 400 and 35, respectively; median annual institutional volume was 100 resections. On unadjusted analyses, several aspects of experience were associated with the outcomes studied, especially for pancreatoduodenectomy; however, none remained significant after multivariable adjustment. Surgeons' profiling showed substantial homogeneity in performance for both pancreatoduodenectomy and distal pancreatectomy., Conclusions: Contemporary data shows that for surgeons operating in high quality settings clinical outcomes are largely independent of indicators of greater experience., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Best management practices for distal pancreatectomy (DP) have not been conclusively defined. The aim of this study was to analyze the practice of DP worldwide and to compare surgeons' behavior with the best available evidence., Methods: A survey assessing management approaches for DP was distributed worldwide, in eight native-language translations. Regions were clustered: North-America, South/Central America, Asia/Australia, and Europe/Africa/Middle East., Results: Overall, 721/797 (91%) responding surgeons (median age = 48; years of experience = 14) indicated their region, representing six continents and 68 nations. Use of minimally-invasive (MI) techniques is diverse-highest in North-America (p < 0.001). Laparoscopy is the most common MI approach, while robotic techniques are rarely performed outside North-America. The preferred means of pancreatic remnant closure is via stapler - more commonly applied in North-America than in Europe/Africa/Middle East. Management techniques for the remnant and other fistula mitigation strategies display significant regional variability. The use of drains is also diverse, with the biggest disparity between North-American and Asian/Australian surgeons (selective and routine drainers, respectively)., Conclusion: There is wide heterogeneity in practices for DP worldwide, which is influenced by the surgeon's region of practice. Variability in practice reflects the lack of solid evidence on the benefit of any given strategy, underlining areas for improvement., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined., Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype., Design, Setting, and Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates., Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy., Main Outcomes and Measures: Overall survival., Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41)., Conclusions and Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined.

Objective: The aim of this study was to elucidate the impact of intraoperative blood loss on outcomes following pancreatoduodenectomy (PD)., Background: The negative impact of intraoperative blood loss on outcomes in PD has long been suspected but not well characterized, particularly those factors that may be within surgeons' control., Methods: From 2001 to 2015, 5323 PDs were performed by 62 surgeons from 17 institutions. Estimated blood loss (EBL) was discretized (0 to 300, 301 to 750, 751 to 1300, and >1300 mL) using optimal scaling methodology. Multivariable regression, adjusted for patient, surgeon, and institutional variables, was used to identify associations between EBL and perioperative outcomes. Factors associated with both increased and decreased EBL were elucidated. The relative impact of surgeon-modifiable contributors was estimated through beta coefficient standardization., Results: The median EBL of the series was 400 mL [interquartile range (IQR) 250 to 600]. Intra-, post-, and perioperative transfusion rates were 15.8%, 24.8%, and 37.2%, respectively. Progressive EBL zones correlated with intra- but not postoperative transfusion in a dose-dependent fashion (P < 0.001), with a key threshold of 750 mL EBL (8.14% vs 40.9%; P < 0.001). Increasing blood loss significantly correlated with poor perioperative outcomes. Factors associated with increased EBL were trans-anastomotic stent placement, neoadjuvant chemotherapy, pancreaticogastrostomy reconstruction, multiorgan or vascular resection, and elevated operative time, of which 38.7% of the relative impact was "potentially modifiable" by the surgeon. Conversely, female sex, small duct, soft gland, minimally invasive approach, pylorus-preservation, biological sealant use, and institutional volume (≥67/year) were associated with decreased EBL, of which 13.6% was potentially under the surgeon's influence., Conclusion: Minimizing blood loss contributes to fewer intraoperative transfusions and better perioperative outcomes for PD. Improvements might be achieved by targeting modifiable factors that influence EBL.

Objective: The aim of this study was to describe characteristics and management approaches for grade B pancreatic fistula (B-POPF) and investigate whether it segregates into distinct subclasses., Background: The 2016 ISGPS refined definition of B-POPF is predicated on various postoperative management approaches, ranging from prolonged drainage to interventional procedures, but the spectrum of clinical severity within this entity is yet undefined., Methods: Pancreatectomies performed at 2 institutions from 2007 to 2016 were reviewed to identify B-POPFs and their treatment strategies. Subclassification of B-POPFs into 3 classes was modeled after the Fistula Accordion Severity Grading System (B1: prolonged drainage only; B2: pharmacologic management; B3: interventional procedures). Clinical and economic outcomes, unique from the ISGPS definition qualifiers, were analyzed across subclasses., Results: B-POPF developed in 320 of 1949 patients (16.4%), and commonly required antibiotics (70.3%), prolonged drainage (67.8%), and enteral/parenteral nutrition (54.7%). Percutaneous drainage occurred in 79 patients (24.7%), always in combination with other strategies. Management of B-POPFs was widely heterogeneous with a median of 2 approaches/patient (range 1 to 6) and 38 various strategy combinations used. Subclasses B1-3 comprised 19.1%, 52.2%, and 28.8% of B-POPFs, respectively, and were associated with progressively worse clinical and economic outcomes. These results were confirmed by multivariable analysis adjusted for clinical and operative factors. Notably, distribution of the B-POPF subclasses was influenced by institution and type of resection (P < 0.001), while clinical/demographic predictors proved elusive., Conclusion: B-POPF is a heterogeneous entity, where 3 distinct subclasses with increasing clinical and economic burden can be identified. This classification framework has potential implications for accurate reporting, comparative research, and performance evaluation.

Objective: The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction., Background: DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored., Methods: DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables., Results: In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts., Conclusion: A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.

Objective: To identify a clinical fistula risk score following distal pancreatectomy., Background: Clinically relevant pancreatic fistula (CR-POPF) following distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive., Methods: This multinational, retrospective study of 2026 DPs involved 52 surgeons at 10 institutions (2001-2016). CR-POPFs were defined by 2016 International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution., Results: CR-POPF occurred following 306 (15.1%) DPs. Risk factors independently associated with CR-POPF included: age (<60 yrs: OR 1.42, 95% CI 1.05-1.82), obesity (OR 1.54, 95% CI 1.19-2.12), hypoalbuminenia (OR 1.63, 95% CI 1.06-2.51), the absence of epidural anesthesia (OR 1.59, 95% CI 1.17-2.16), neuroendocrine or nonmalignant pathology (OR 1.56, 95% CI 1.18-2.06), concomitant splenectomy (OR 1.99, 95% CI 1.25-3.17), and vascular resection (OR 2.29, 95% CI 1.25-3.17). After adjusting for inherent risk between cases by multivariable regression, the following were not independently associated with CR-POPF: method of transection, suture ligation of the pancreatic duct, staple size, the use of staple line reinforcement, tissue patches, biologic sealants, or prophylactic octreotide. Intraoperative drainage was associated with a greater fistula rate (OR 2.09, 95% CI 1.51-3.78) but reduced fistula severity (P < 0.001)., Conclusions: From this large analysis of pancreatic fistula following DP, CR-POPF occurrence cannot be reliably predicted. Opportunities for developing a risk score model are limited for performing risk-adjusted analyses of mitigation strategies and surgeon performance.

Background: Recent data illustrates improved outcomes when adhering to early drain removal following pancreatoduodenectomy (PD). This study aims to explore the potential benefits of expanding the timeframe for early drain removal., Methods: Six hundred forty PDs were originally managed by selective drain placement and early removal. Outcomes were reappraised in the framework of a novel proposal; intraoperative drains were omitted based on a low-risk profile (Fistula Risk Score 0-2), followed by drain removal at PODs 1, 3, and 5 if drain fluid amylase (DFA) fell below specific cutoffs based on optimized negative predictive values (NPV) for clinically relevant postoperative pancreatic fistula (CR-POPF). Characteristics of the remaining cohort with drains in situ on POD5 were examined using multivariable analysis (MVA)., Results: Intraoperative FRS would preclude drains from 230 (35.9%) negligible/low-risk cases with a cohort CR-POPF rate of 1.7%. Of the remaining patients, 30.5% would have drains removed on POD1 based on a DFA threshold of 300 IU/L (NPV = 98.4%), demonstrating a 1.6% CR-POPF rate. On POD3, drains could be removed in the residual cohort from 21.1% of patients with DFA ≤ 150 IU/L (NPV = 96.6%), reflecting a 3.4% CR-POPF rate. On POD5, a DFA threshold of 50 IU/L (NPV = 84%) identified 16.3% more patients whose drains could be removed. The remaining cohort (POD5 DFA > 50 IU/L), "enriched" for fistula development and reflecting just 18.4% of the original patients, displays a 61% CR-POPF rate. Among these patients on POD5, a DFA threshold > 2000 IU/L best predicted subsequent CR-POPF (PPV = 89.5%), and MVA revealed a positive association between pancreatic cancer/pancreatitis (OR = 4.37, p = 0.022) and longer operations (OR = 3.74, p = 0.014) with CR-POPF development., Conclusion: Early drain removal is a dynamic concept and can be employed throughout the postoperative time course using conditional thresholds to better identify patients at risk for CR-POPF.

Objectives: The aim of this study was to evaluate the impact of Animated Pancreas Patient (APP) educational modules (APP website and YouTube) on pancreas education, awareness, and health outcomes., Methods: This was a retrospective study of APP metrics data from September 2013 to October 2017. We evaluated audience reach (number of visit sessions, unique visitors, page views) and calculated top views by media type (animation, expert video, patient video, and slide show) and top retention videos from the modules. We also assessed the educational impact through learner feedback survey., Results: The APP had 1,475,252 views (547,693 unique visitors, 63.1% in United States) during the study period. Most popular topic viewed among the animations was "Role and Anatomy of the Pancreas" (n = 361,116), and most common expert video viewed was "Chronic Pancreatitis: What Foods and Beverages Should I Avoid?" (n = 31,667). Participants who completed the online feedback survey reported knowledge gains and commitments to change., Conclusions: Pancreas education in visual formats of learning provided by APP demonstrated wide reach and has substantial potential to inform and impact behaviors of patients and caregivers. Continued efforts should be made to provide patient resources that address health literacy and patient education and respond to patient needs for better quality of life and improved health outcomes in pancreatic diseases.

Background: Improvements in surgical outcomes are predicated on recognizing effective practices with subsequent adaptation. It is unknown whether risk assessment for pancreatic fistula (clinically relevant postoperative pancreatic fistula [CR-POPF]) after pancreaticoduodenectomy (PD) translates to improved patient outcomes at the practice level., Study Design: A prospectively collected, single-surgeon career experience (2003 to 2018) of 455 consecutive pancreatectomies (303 PDs and 152 distal pancreatectomies) was examined. Analysis occurred during 4 eras of practice: learning curve for PD (n = 50); development of the Fistula Risk Score (n = 48); reactive, data-driven adjustments of anastomotic stent use (n = 94); and omission of prophylactic octreotide with adoption of selective drainage (n = 111). Observed to expected ratios of CR-POPF were calculated using a multi-institutional derivation set (5,379 PDs)., Results: After adjustment for increasing fistula risk across the 4 eras (p = 0.016), the risk-adjusted CR-POPF rate declined significantly (observed to expected ratio 1.42→1.28→1.01→0.30; p < 0.001). Literature-driven changes in fistula mitigation strategies likewise led to reductions in the overall complication burden (Postoperative Morbidity Index: 0.20→0.24→0.25→0.15; p = 0.015) and resource use (therapeutic antibiotics: p = 0.019; hospital readmission: p = 0.006; postoperative transfusion: p = 0.007). In contrast, the CR-POPF rate after distal pancreatectomy, for which no validated risk-adjustment process exists, did not vary (approximately 12%; p = 0.878)., Conclusions: Patient outcomes for PD can be optimized by risk-adjusted evaluation and deliberate modification of practice., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)