Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.

The pancreas has two main functions: to produce and secrete digestive enzymes (exocrine function) and to produce hormones that regulate blood glucose and splanchnic secretion (endocrine function). The endocrine and exocrine portions of the pancreas are central regulators in digestion and metabolism, with continuous crosstalk between their deeply interconnected components, which plays a role in disease. Pancreatic neoplasms, inflammation, trauma, and surgery can lead to the development of type 3c diabetes when an insult simultaneously damages both acini and islets, leading to exocrine and endocrine dysfunction. In diabetes mellitus patients, pancreatic exocrine insufficiency is highly prevalent, yet little is known about the associations between diabetes mellitus and pancreatic exocrine function. This review aims to provide an overview of the physiology of the pancreas, summarize the pathophysiology and diagnostic work-up of pancreatic exocrine insufficiency, and explore the relationships between exocrine pancreatic insufficiency and diabetes mellitus.

Background: Intraductal papillary mucinous neoplasms (IPMNs) display four histological subtypes: gastric foveolar, pancreaticobiliary, intestinal, and oncocytic. All of these subtypes harbor a different risk of cancer development. The clinical impact of these subtypes concerning the occurrence of high-grade dysplasia (HGD)/cancer (C) in specific morphological types, such as branch-duct (BD), main-duct (MD), and mixed-type (MT) IPMNs, has been less investigated. Hence, our aim was to investigate the prevalence of histological subtypes and their possible association with HGD/C concerning morphologically different IPMNs. Methods: This was a retrospective review of demographics, risk factors, and histological features in a surgical cohort of patients having undergone resection for suspect malignant IPMNs at a high-volume tertiary center from 2007 to 2017. Results: A total of 273 patients were resected for IPMNs from during the study period, of which 188 were included in the final analysis. With sex- and age-adjusted multivariable logistic regression analysis across the entire cohort, gastric foveolar subtypes were associated with a reduced prevalence of HGD/C (OR = 0.30; 0.11–0.81, 95% CI, 95%CI; p = 0.01). With univariable logistic regression analysis, in the BD-IPMN subgroup, the pancreaticobiliary subtype was associated with an increased prevalence of HGD/C (OR = 18.50, 1.03–329.65, 95% CI; p = 0.04). In MD- and MT-IPMNs, the gastric foveolar subtype was associated with a decreased prevalence of HGD/cancer (OR = 0.30, 0.13–0.69, 95% CI; p = 0.004). Conclusions: In MD and MT-IPMNs, the gastric-foveolar subtype is associated with a lower prevalence of HGD/C, possibly identifying in such a high-risk group, a subgroup with more indolent behavior. In BD-IPMNs, the pancreaticobiliary subtype is associated with a higher prevalence of HGD/C, conversely identifying among those patients, a subgroup deserving special attention.

Objective: To validate the prognostic value of the PAncreatic NeoAdjuvant MAssachusetts (PANAMA) score and to determine its predictive ability for survival benefit derived from adjuvant treatment in patients after resection of pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant FOLFIRINOX. Background: The PANAMA score was developed to guide prognostication in patients after neoadjuvant therapy and resection for PDAC. As this score focuses on the risk for residual disease after resection, it might also be able to select patients who benefit from adjuvant after neoadjuvant therapy. Methods: This retrospective international multicenter study is endorsed by the European-African Hepato-Pancreato-Biliary Association. Patients with PDAC who underwent resection after neoadjuvant FOLFIRINOX were included. Mantel-Cox regression with interaction analysis was performed to assess the impact of adjuvant chemotherapy. Results: Overall, 383 patients after resection of PDAC following neoadjuvant FOLFIRINOX were included of whom 187 (49%), 137 (36%), and 59 (15%) had a low-risk, intermediate-risk, and high-risk PANAMA-score, respectively. Discrimination in median overall survival (OS) was observed stratified by risk groups (48.5, 27.6, and 22.3 months, log-rank P _{low-intermediate} = 0.004, log-rank P _{intermediate-high} = 0.027). Adjuvant therapy was not associated with an OS difference in the low-risk group [hazard ratio (HR): 1.50, 95% CI: 0.92–2.50], whereas improved OS was observed in the intermediate (HR: 0.58, 95% CI: 0.34–0.97) and high-risk groups (HR: 0.47, 95% CI: 0.24–0.94; P interaction = 0.008). Conclusions: The PANAMA 3-tier risk groups (low-risk, intermediate-risk, and high-risk, available through pancreascalculator.com) correspond with differential survival in patients with resected PDAC following neoadjuvant FOLFIRINOX. The risk groups also differentiate between survival benefits associated with adjuvant treatment, with only the intermediate- and high-risk groups associated with improved OS.

Objective: Assess anticoagulation practice and portal vein thrombosis (PVT) risk following pancreaticoduodenectomy (PD) or total pancreatectomy (TP) with venous resection (VR). Background: Retrospective studies suggest an increased risk of PVT following PD/TP with VR. However, anticoagulation practice is variable and its efficacy at preventing PVT is unknown. Methods: This multicentre cohort study (Europe, USA, Mexico, Turkey, Australia, New Zealand) included consecutive patients undergoing PD/TP with VR between 2018-2022. A 1:1 age and sex matched cohort undergoing PD/TP without VR was also collected to assess PVT risk without VR. Results: Among 972 patients who underwent PD/TP with VR, 259 (26.6%) received inpatient therapeutic anticoagulation and 242 (25.0%) were discharged on therapeutic anticoagulation. Thirty-day, 90-day and one-year PVT risk following VR was 5.1%, 7.3%, and 11.6%, versus 1.0%, 1.3% and 2.6% in patients without VR (P<0.001). Predictors of 90-day PVT included prior history of venous thromboembolism (odds ratio [OR] 2.67), VR type (OR 2.29, 6.28, 6.90 and 23.75 for type 1-4 VR, P<0.001) and graft material (OR 0.78, 0.94, 5.28, 4.90 and 5.99 for peritoneal, autologous vein, cadaveric vein, bovine and synthetic grafts, P<0.001). Postoperative therapeutic anticoagulation reduced 30-day PVT risk (OR 0.06, P90-day PVT risk (OR 1.23, P=0.466). The strongest predictor of >90-day PVT was cancer recurrence (OR 3.96, P<0.001). Conclusions: VR increases PVT risk following PD/TP, with technical factors influencing 90-day PVT. The benefits of early postoperative anticoagulation in preventing PVT post-VR remain unclear.