Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy.

BACKGROUND: The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS: Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS: In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS: Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.

Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

The utility of synoptic operation reports in colorectal surgery: a systematic review.

PURPOSE: Accurate documentation is crucial in surgical patient care. Synoptic reports (SR) are structured checklist-based reports that offer a standardised alternative to traditional narrative reports (NR). This systematic review aims to assess the completeness of SR compared to NR in colorectal cancer (CRC) surgery. Secondary outcomes include the time to completion, surgeon satisfaction, educational value, research value, and barriers to implementation. METHODS: Prospective or retrospective studies that assessed SR compared to NR in colorectal cancer surgery procedures were identified through a systematic search of Ovid MEDLINE, Embase (Ovid), CIHNAL Plus with Full Text (EBSCOhost), and Cochrane. One thousand two articles were screened, and eight studies met the inclusion criteria after full-text review of 17 papers. RESULTS: Analysis included 1797 operative reports (NR, 729; SR, 1068). Across studies reporting this outcome, the completeness of documentation was significantly higher in SR (P < 0.001). Reporting of secondary outcomes was limited, with a predominant focus on research value. Several studies demonstrated significantly reduced data extraction times when utilising SR. Surgeon satisfaction with SR was high, and these reports were seen as valuable tools for research and education. Barriers to implementation included integrating SR into existing electronic medical records (EMR) and surgeon concerns regarding increased administrative burden. CONCLUSIONS: SR offer advantages in completeness, data extraction, and communication compared to NR. Surgeons perceive them as beneficial for research, quality improvement, and teaching. This review supports the necessity for development of user-friendly SR that seamlessly integrate into pre-existing EMRs, optimising patient care and enhancing the quality of CRC surgical documentation.

Standardizing process in acute biliary disease.

INTRODUCTION: The perioperative management of biliary disease (BD) is variable across institutions with suboptimal outcomes for patients and health care systems. This results in inefficient utilization of limited resources. The aim of the current study was to identify modifiable factors impacting patients' time to theater, intraoperative time, and time to discharge as the constituents of length of stay to guide creation of a perioperative management protocol to address this variability. METHODS: Data were prospectively captured at Christchurch Hospital for all adult patients presenting for cholecystectomy between May 2015 and May 2022. Pre, post, and intraoperative factors were assessed for their impact on time to theater, operative time, and postoperative hours to discharge. RESULTS: Four thousand five hundred seventy-seven patients underwent cholecystectomy during the study period, of which 2807 (61%) were acute presentations and made up the cohort for analysis. Time to theater was significantly impacted by preoperative imaging type, while operative grade and the procedure type had the most clinically significant impact on operative time. Postoperatively time to discharge was significantly impacted by drain placement. CONCLUSIONS: Standardizing management of BD would likely result in significant savings for the health care system and improved outcomes for patients. The data seen here evidence the importance of appropriate imaging selection, intraoperative difficulty operative grade identification, and low suction drain selection. These data have been incorporated in a perioperative management protocol as standardization of care across the patient workflow in BD is a sensible approach for ensuring optimal use of scarce resources.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

The artery first technique: re-examining the critical view of safety during laparoscopic cholecystectomy.

INTRODUCTION: Significant discrepancies exist between surgeon-documented and actual rates of critical view of safety (CVS) achievement on retrospective review following laparoscopic cholecystectomy. This discrepancy may be due to surgeon utilisation of the artery first technique (AFT), an exception to the CVS first described by Strasberg et al. The present study aims to characterise the use of the AFT, hypothesising it is used as an adjunct in difficult dissections to maximise exposure of the hepato-cystic triangle ensuring safe cholecystectomy. METHODS: Prospective digital recording of the operative procedure of patients' undergoing laparoscopic cholecystectomy were undertaken at Christchurch Public Hospital, New Zealand and North Shore Private Hospital, Sydney, Australia. Videos were uploaded to Touch Surgery™ Enterprise. Difficulty was graded, annotated and indications for the AFT quantified using a standardised protocol. RESULTS: A total of 275 annotated procedures were included in this study. The AFT was employed in 54 (20%) patients; in 13 (24%) patients for bleeding, in 35 (65%) patients where windows one and two were visible, and in 6 (11%) patients no windows were visible within the hepato-cystic triangle. There were significant differences in utilisation across operative grade and by seniority of operator (p < 0.005). CONCLUSIONS: The data presented here demonstrate the AFT is frequently used, particularly with Grade 3 cholecystectomy. However, more data are needed to confirm the utility and safety of this approach. Analysis of the AFT shows that to understand and improve safety in laparoscopic cholecystectomy appreciating how the operation was undertaken and not just that the CVS was achieved is crucial.

Clinical validation of the international study group of pancreatic surgery (ISGPS) definition for post-pancreatectomy acute pancreatitis.

BACKGROUND: The diagnosis of postoperative or post-pancreatectomy acute pancreatitis (PPAP) is controversial. In 2021, the International Study Group of Pancreatic Surgery (ISGPS) published the first unifying definition and grading system for PPAP. This study sought to validate recent consensus criteria, using a cohort of patients undergoing pancreaticoduodenectomy (PD) in a high-volume pancreaticobiliary specialty unit. METHODS: All consecutive patients undergoing PD at a tertiary referral centre between January 2016 and December 2021 were retrospectively reviewed. Patients with serum amylase recorded within 48h from surgery were included for analysis. Postoperative data were extracted and evaluated against the ISGPS criteria, including the presence of postoperative hyperamylasaemia, radiologic features consistent with acute pancreatitis, and clinical deterioration. RESULTS: A total of 82 patients were evaluated. The overall incidence of PPAP was 32% (26/82) in this cohort, of which 3/26 demonstrated postoperative hyperamylasaemia and 23/26 had clinically relevant PPAP (Grade B or C) when correlated radiologic and clinical criteria. CONCLUSIONS: This study is among the first to apply the recently published consensus criteria for PPAP diagnosis and grading to clinical data. While the results support their utility in establishing PPAP as a distinct post-pancreatectomy complication, there remains a need for future large-scale validation studies.

Postpancreatectomy Acute Pancreatitis (PPAP): Definition and Grading From the International Study Group for Pancreatic Surgery (ISGPS).

OBJECTIVE: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison. BACKGROUND: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking. METHODS: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021. RESULTS: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative serum hyperamylasemia (POH) greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications. DISCUSSIONS: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies.

Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis.

BACKGROUND: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. METHODS: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. RESULTS: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. CONCLUSION: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.

Use of prospective video analysis to understand the impact of technical difficulty on operative process during laparoscopic cholecystectomy.

BACKGROUND: An understanding of the impact of operative difficulty on operative process in laparoscopic cholecystectomy is lacking. The aim of the present study was to prospectively analyse digitally recorded laparoscopic cholecystectomy to assess the impact of operative technical difficulty on operative process. METHODS: Video of laparoscopic cholecystectomy procedures performed at Christchurch Hospital, NZ and North Shore Private Hospital, Sydney Australia were prospectively recorded. Using a framework derived from a previously published standard process video was annotated using a standardized template and stratified by operative grade to evaluate the impact of grade on operative process. RESULTS: 317 patients had their laparoscopic cholecystectomy operations prospectively recorded. Seventy one percent of these videos (n = 225) were annotated. Single ICC of operative grade was 0.760 (0.663-0.842 p < 0.010). Median operative time, rate of operative errors significantly increased and rate of CVS decreased with increasing operative grade. Significant differences in operative anatomy, operative process and instrumentation were seen with increasing grade. CONCLUSION: Operative technical difficulty is accurately predicted by operative grade and this impacts on operative process with significant implications for both surgeons and patients. Consequently operative grade should be documented routinely as part of a culture of safe laparoscopic cholecystectomy.

External validation of postoperative pancreatic fistula prediction scores in pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores. METHODS: Areas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models. RESULTS: Systematic review identified 34 risk scores, of which six had been subjected to external validation, and so included in the meta-analysis, (Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores). Overall predictive accuracies were similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%. CONCLUSION: Most risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.

The Challenges of Implementing Artificial Intelligence into Surgical Practice.

BACKGROUND: Artificial intelligence is touted as the future of medicine. Classical algorithms for the detection of common bile duct stones (CBD) have had poor clinical uptake due to low accuracy. This study explores the challenges of developing and implementing a machine-learning model for the prediction of CBD stones in patients presenting with acute biliary disease (ABD). METHODS: All patients presenting acutely to Christchurch Hospital over a two-year period with ABD were retrospectively identified. Clinical data points including lab test results, demographics and ethnicity were recorded. Several statistical techniques were utilised to develop a machine-learning model. Issues with data collection, quality, interpretation and barriers to implementation were identified and highlighted. RESULTS: Issues with patient identification, coding accuracy, and implementation were encountered. In total, 1315 patients met inclusion criteria. Incorrect international classification of disease 10 (ICD-10) coding was noted in 36% (137/382) of patients recorded as having CBD stones. Patients with CBD stones were significantly older and had higher aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and gamma-glutamyl transferase (GGT) levels (p < 0.001). The no information rate was 81% (1070/1315 patients). The optimum model developed was the gradient boosted model with a PPV of 67%, NPV of 87%, sensitivity of 37% and a specificity of 96% for common bile duct stones. CONCLUSION: This paper highlights the utility of machine learning in predicting CBD stones. Accuracy is limited by current data and issues do exist around both the ethics and practicality of implementation. Regardless, machine learning represents a promising new paradigm for surgical practice.

Safe Cholecystectomy Multi-society Practice Guideline and State of the Art Consensus Conference on Prevention of Bile Duct Injury During Cholecystectomy.

BACKGROUND: BDI is the most common serious complication of laparoscopic cholecystectomy. To address this problem, a multi-society consensus conference was held to develop evidenced-based recommendations for safe cholecystectomy and prevention of BDI. METHODS: Literature reviews were conducted for 18 key questions across 6 broad topics around cholecystectomy directed by a steering group and subject experts from 5 surgical societies (Society of Gastrointestinal and Endoscopic Surgeons, Americas Hepato-Pancreato-Biliary Association, International Hepato-Pancreato-Biliary Association, Society for Surgery of the Alimentary Tract, and European Association for Endoscopic Surgery). Evidence-based recommendations were formulated using the grading of recommendations assessment, development, and evaluation methodology. When evidence-based recommendations could not be made, expert opinion was documented. A number of recommendations for future research were also documented. Recommendations were presented at a consensus meeting in October 2018 and were voted on by an international panel of 25 experts with greater than 80% agreement considered consensus. RESULTS: Consensus was reached on 17 of 18 questions by the guideline development group and expert panel with high concordance from audience participation. Most recommendations were conditional due to low certainty of evidence. Strong recommendations were made for (1) use of intraoperative biliary imaging for uncertainty of anatomy or suspicion of biliary injury; and (2) referral of patients with confirmed or suspected BDI to an experienced surgeon/multispecialty hepatobiliary team. CONCLUSIONS: These consensus recommendations should provide guidance to surgeons, training programs, hospitals, and professional societies for strategies that have the potential to reduce BDIs and positively impact patient outcomes. Development of clinical and educational research initiatives based on these recommendations may drive further improvement in the quality of surgical care for patients undergoing cholecystectomy.

Safe cholecystectomy multi-society practice guideline and state-of-the-art consensus conference on prevention of bile duct injury during cholecystectomy.

BACKGROUND: Bile duct injury (BDI) is the most common serious complication of laparoscopic cholecystectomy. To address this problem, a multi-society consensus conference was held to develop evidenced-based recommendations for safe cholecystectomy and prevention of BDI. METHODS: Literature reviews were conducted for 18 key questions across six broad topics around cholecystectomy directed by a steering group and subject experts from five surgical societies (SAGES, AHPBA IHPBA, SSAT, and EAES). Evidence-based recommendations were formulated using the GRADE methodology. When evidence-based recommendations could not be made, expert opinion was documented. A number of recommendations for future research were also documented. Recommendations were presented at a consensus meeting in October 2018 and were voted on by an international panel of 25 experts with greater than 80% agreement considered consensus. RESULTS: Consensus was reached on 17 of 18 questions by the Guideline Development Group (GDG) and expert panel with high concordance from audience participation. Most recommendations were conditional due to low certainty of evidence. Strong recommendations were made for (1) use of intraoperative biliary imaging for uncertainty of anatomy or suspicion of biliary injury; and (2) referral of patients with confirmed or suspected BDI to an experienced surgeon/multispecialty hepatobiliary team. CONCLUSION: These consensus recommendations should provide guidance to surgeons, training programs, hospitals, and professional societies for strategies that have the potential to reduce BDIs and positively impact patient outcomes. Development of clinical and educational research initiatives based on these recommendations may drive further improvement in the quality of surgical care for patients undergoing cholecystectomy.

Pancreatic grade 3 neuroendocrine tumors behave similarly to neuroendocrine carcinomas following resection: a multi-center, international appraisal of the WHO 2010 and WHO 2017 staging schema for pancreatic neuroendocrine lesions.

BACKGROUND: In 2017, the WHO updated their 2010 classification of pancreatic neuroendocrine tumors, introducing a well-differentiated, highly proliferative grade 3 tumor, distinct from neuroendocrine carcinomas. The aim of this study was to investigate the clinical significance of this update in a large cohort of resected tumors. METHODS: Using a multicenter, international dataset of patients with pancreatic neuroendocrine lesions, patients were classified both according to the WHO 2010 and 2017 schema. Multivariable survival analyses were performed, and the models were evaluated for discrimination ability and goodness of fit. RESULTS: Excluding patients with a known germline MEN1 mutation and incomplete data, 544 patients were analyzed. The performance of the WHO 2010 and 2017 models was similar, however surgically resected grade 3 tumors behaved very similarly to neuroendocrine carcinomas. CONCLUSION: The addition of a grade 3 NET classification may be of limited utility in surgically resected patients, as these lesions have similar postoperative survival compared to carcinomas. While the addition may allow for a more granular evaluation of novel treatment strategies, surgical intervention for high grade tumors should be considered judiciously.

Electronic informed consent: the need to redesign the consent process for the digital age.

The delivery of healthcare, which includes the informed consent process, is moving to a digital environment. This change in informed consent delivery will be associated with opportunities, risks and also unintentional consequences. Physicians are well placed to contribute to the ongoing dialogue about what is needed to make the informed consent process fit for purpose, in the digital age.

Acinar cell density at the pancreatic resection margin is associated with post-pancreatectomy pancreatitis and the development of postoperative pancreatic fistula.

BACKGROUND: There has been recent evidence supporting post-pancreatectomy pancreatitis as a factor in the development of postoperative pancreatic fistula (POPF). The aims of this study were to evaluate: (i) the correlation of the acinar cell density at the pancreatic resection margin with the intra-operative amylase concentration (IOAC) of peri-pancreatic fluid, postoperative pancreatitis, and POPF; and (ii) the association between postoperative pancreatitis on the first postoperative day and POPF. METHODS: Consecutive patients who underwent pancreatic resection between June 2016 and July 2017 were included for analysis. Fluid for IOAC was collected, and amylase concentration was determined in drain fluid on postoperative days 1, 3, and 5. Serum amylase and lipase and urinary trypsinogen-2 concentrations were determined on the first postoperative day. Histology slides of the pancreatic resection margin were scored for acinar cell density. RESULTS: Sixty-one patients were included in the analysis. Acinar cell density significantly correlated with IOAC (r = 0.566, p < 0.001), and was significantly associated with postoperative pancreatitis (p < 0.001), and POPF (p = 0.003). Postoperative pancreatitis was significantly associated with the development of POPF (OR 17.81, 95%CI 2.17-145.9, p = 0.001). DISCUSSION: The development of POPF may involve a complex interaction between acinar cell density, immediate leakage of pancreatic fluid, and postoperative pancreatitis.