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Background: An increasing body of evidence suggests that microbiota may promote progression of pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that gammaproteobacteria (such as Klebsiella pneumoniae) influence survival in PDAC, and that quinolone treatment may attenuate this effect. Methods: This was a retrospective study of patients from the Massachusetts General Hospital (USA) and Ludwig-Maximilians-University (Germany) who underwent preoperative treatment and pancreatoduodenectomy for locally advanced or borderline resectable PDAC between January 2007 and December 2017, and for whom a bile culture was available. Associations between tumour characteristics, survival data, antibiotic use and results of intraoperative bile cultures were investigated. Survival was analysed using Kaplan-Meier curves and Cox regression analysis. Results: Analysis of a total of 211 patients revealed that an increasing number of pathogen species found in intraoperative bile cultures was associated with a decrease in progression-free survival (PFS) (-1·9 (95 per cent c.i. -3·3 to -0·5) months per species; P = 0·009). Adjuvant treatment with gemcitabine improved PFS in patients who were negative for K. pneumoniae (26·2 versus 15·3months; P= 0·039), but not in those who tested positive (19·5 versus 13·2 months; P= 0·137). Quinolone treatment was associated with improved median overall survival (OS) independent of K. pneumoniae status (48·8 versus 26·2months; P= 0·006) and among those who tested positive for K. pneumoniae (median not reached versus 18·8 months; P= 0·028). Patients with quinolone-resistant K. pneumoniae had shorter PFS than those with quinolone-sensitive K. pneumoniae (9·1 versus 18·8 months; P= 0·001). Conclusion: K. pneumoniae may promote chemoresistance to adjuvant gemcitabine, and quinolone treatment is associated with improved survival. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s).)

Background: Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival., Methods: Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed., Results: In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00)., Conclusion: A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown., Methods: Consecutive patients undergoing pancreatic resection (2010-2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN)., Results: 415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574)., Conclusions: Invasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. All rights reserved.)

Objective: This international multicenter 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 intraductal papillary mucinous neoplasm (IPMN)., Background: Recurrence patterns and treatment of recurrence postresection of adenocarcinoma arising from IPMN are poorly explored., Methods: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 and December 2020 at 18 pancreatic centers were identified. Survival analysis was performed using the Kaplan-Meier log-rank test and multivariable logistic regression by Cox-Proportional Hazards modeling. End points were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided)., Results: Four hundred fifty-nine patients were included (median, 70 years; interquartile range, 64-76; male, 54%) with a median follow-up of 78.1 months. Recurrence occurred in 209 patients [45.5%; median time to recurrence, 12.8 months; early recurrence (within 1 years), 23.2%]. Eighty-three (18.1%) patients experienced a local regional recurrence, and 164 (35.7%) patients experienced a distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (hazard ratio 1.09; P =0.669) One hundred 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 locations of recurrence ( P =0.401)., Conclusions: 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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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 Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC., Summary Background Data: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce., Methods: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC., Results: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695)., Conclusions: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns., Competing Interests: Conflicts of interest: None, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Previous studies showed that bacterial contamination of surgical drains was associated with higher morbidity and mortality following pancreaticoduodenectomy (PD). However, there is still no agreement on the routine use of fluid drainage cultures in the management of patients underwent PD. Therefore, we aimed to clarify the role of surgical drain bacterial contamination in predicting patients' postoperative course., Method: Single-centre study including patients underwent PD at Humanitas Research Hospital (2010-2021). Preoperative, intraoperative and postoperative data were collected. Routinely performed fluid drain cultures on postoperative day (POD) 5 were analyzed and compared among patients throughout the cohort., Results: A total of 825 patients were analyzed. Bacterial contamination of surgical drains was observed in 420 (50.9 %) patients and it was found to be associated with a higher rate of B/C grade pancreatic fistula (POPF) (P < 0.001), Clavien-Dindo≥3 (P < 0.001), 30-day mortality (P = 0.011), wound infection (P < 0.001), relaparotomies (P = 0.003) and greater length of hospital stay (LOS) (P < 0.001). Also, E. coli surgical drain contamination was demonstrated to double the risk of B/C grade POPF development (OR = 1.628, 95 % IC = 1.009-2.625, P = 0.046). Finally, preoperative biliary drainage (OR = 2.474, 95 % IC = 1.855-3.298, P < 0.001), age ≥75 years old (OR = 1.492, 95 % IC = 1.077-2.067, P = 0.016) and isolated Roux-en-Y pancreaticojejunostomy (OR = 1.639, 95 % IC = 1.229-2.188, P < 0.001) were identified as risk factors for surgical drains bacterial contamination., Conclusion: Bacterial contamination of surgical drains predicts the development of B/C grade POPF and other major complications after PD. Therefore, we suggest the routine use of fluid drain cultures following PD., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The type and the extent of surgery is still debatable for intraductal papillary mucinous neoplasm (IPMN). Intraoperative pancreatoscopy (IOP) allows the visualization of the main pancreatic duct (MPD) in its entire length and could help determine the extent of MPD involvement and the type and extent of pancreatic resection. However, current guidelines do not advise its routine use as there is a lack of evidence supporting its safety and feasibility. The present study aims to perform a scoping review of published evidence on the safety and feasibility of IOP in IPMN surgical management., Methods: We systematically searched PubMed, Cochrane, Medline and EMbase to identify studies reporting the use of IOP in IPMN surgical management. The research was completed in June 2023. Data extracted included patient selection criteria, demographics, safety of the procedure, intraoperative findings, impact on surgical strategy, histology results and postoperative outcomes., Results: Four retrospective and one prospective study were included in this scoping review. A total of 142 patients had IOP. The selection criteria for inclusion were heterogenous, with one out of five studies including branch duct (BD), main duct (MD) and mixed type IPMN. Indications for IOP and surgical resection were only reported in two studies. A median of seven outcomes (range 5-8) was described, including the type of surgical resection, additional lesions and change of surgical plan, and complications after IOP. IOP showed additional lesions in 48 patients (34%) and a change of surgical plan in 48(34%). No IOP-related complications were reported., Conclusions: This scoping review suggests IOP is safe and identifies additional lesions impacting the surgical strategy for IPMN. However, the included studies were small and heterogeneous regarding IPMN definition and indications for surgery and IOP. There is a need for a large multi-centre prospective study to determine the role of IOP and its impact on surgical strategy for IPMN., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Backgrounds/aims: Patients who undergo pancreatic surgery with venous resection have high rates of morbidity/mortality. Also, they are high-risk for postoperative venous thromboembolism. Whether this group should be routinely anticoagulated is unknown. This study aimed to establish current anticoagulation practices., Methods: A survey (https://form.jotform.com/220242489107048) was sent out to pancreatic surgeons. Questions covered center volume, venous resection/reconstruction techniques and anticoagulation policies., Results: Sixty-five centers from 17 countries responded. Following a "side-bite" venous resection with a patch repair, 40% used an autologous vein patch, 27% used peritoneum, and 27% used a bovine patch. After formally resecting a segment of vein, 17% of centers used an interposition graft (IG). Left renal vein (41%) and polytetrafluoroethylene (73%) grafts were the most commonly used autologous and prosthetic IGs, respectively. Following a prosthetic IG, an autologous IG, and a "side-bite" resection, 59%, 28%, and 19% of centers provided therapeutic anticoagulation, respectively (66% used low molecular-weight heparin). The duration of therapy provided varied from inpatient stay only (14%) to six months (32%)., Conclusions: Our global survey indicates that anticoagulation practices are highly variable. Centers do not agree on when to anticoagulate, how to anticoagulate, or the duration of therapy. A robust trial is required to provide clarity.

Objectives: Natural language processing (NLP) algorithms can interpret unstructured text for commonly used terms and phrases. Pancreatic pathologies are diverse and include benign and malignant entities with associated histologic features. Creating a pancreas NLP algorithm can aid in electronic health record coding as well as large database creation and curation., Methods: Text-based pancreatic anatomic and cytopathologic reports for pancreatic cancer, pancreatic ductal adenocarcinoma, neuroendocrine tumor, intraductal papillary neoplasm, tumor dysplasia, and suspicious findings were collected. This dataset was split 80/20 for model training and development. A separate set was held out for testing purposes. We trained using convolutional neural network to predict each heading., Results: Over 14,000 reports were obtained from the Mass General Brigham Healthcare System electronic record. Of these, 1252 reports were used for algorithm development. Final accuracy and F1 scores relative to the test set ranged from 95% and 98% for each queried pathology. To understand the dependence of our results to training set size, we also generated learning curves. Scoring metrics improved as more reports were submitted for training; however, some queries had high index performance., Conclusions: Natural language processing algorithms can be used for pancreatic pathologies. Increased training volume, nonoverlapping terminology, and conserved text structure improve NLP algorithm performance., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas., Summary of Background Data: Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4)., Methods: This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms., Results: Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5., Conclusions: This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice., Competing Interests: The authors report no conflicts of interest, (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or therapeutic development. Here, we construct a high-resolution molecular landscape of the cellular subtypes and spatial communities that compose PDAC using single-nucleus RNA sequencing and whole-transcriptome digital spatial profiling (DSP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment naive. We uncovered recurrent expression programs across malignant cells and fibroblasts, including a newly identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities with distinct contributions from malignant, fibroblast and immune subtypes: classical, squamoid-basaloid and treatment enriched. Our refined molecular and cellular taxonomy can provide a framework for stratification in clinical trials and serve as a roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Academic hospitals must train future surgeons, but whether residents could negatively affect the outcomes of major procedures is a matter of concern. The aim of this study is to assess if pancreatic surgery is a safe teaching model., Methods: Outcomes of 1230 major pancreatic resections performed at a high-volume pancreatic teaching hospital between 2015 and 2018 were compared according to the first surgeon type, attending vs resident., Results: Residents performed a selection of 132 (16%) pancreaticoduodenectomies (PD) and 46 (11%) distal pancreatectomies (DP). For PD, pancreatic fistula (25% vs 0, p < 0.001), biliary fistula (7.1% vs 3.5%, p = 0.04) and operative time (400 vs 390 min, p < 0.001) were lower for residents but post-pancreatectomy hemorrhage was higher (20.5% vs 13% p = 0.024). For DP, pancreatic fistula rate was lower for residents (31.7% vs 17.5% p = 0.046). There was no difference in terms of lymph nodes retrieval both for PDs and DPs, while the R1 resections were more frequent among PDs performed by attending surgeons (31.5% vs 15.7%, p = 0.023)., Conclusion: The active participation of residents does not negatively affect outcomes of major pancreatic resections in a high-volume center. By means of case selection and continuous tutoring, pancreatic surgery represents a safe and valid teaching model., (Copyright © 2020. Published by Elsevier Ltd.)

Background and Aims: Advances in cross-sectional imaging have resulted in increased detection of intraductal papillary mucinous neoplasms (IPMNs), and their management remains controversial. At present, there is no reliable noninvasive method to distinguish between indolent and high risk IPMNs. We performed extracellular vesicle (EV) analysis to identify markers of malignancy in an attempt to better stratify these lesions., Methods: Using a novel ultrasensitive digital extracellular vesicle screening technique (DEST), we measured putative biomarkers of malignancy (MUC1, MUC2, MUC4, MUC5AC, MUC6, Das-1, STMN1, TSP1, TSP2, EGFR, EpCAM, GPC1, WNT-2, EphA2, S100A4, PSCA, MUC13, ZEB1, PLEC1, HOOK1, PTPN6, and FBN1) in EV from patient-derived cell lines and then on circulating EV obtained from peripheral blood drawn from patients with IPMNs. We enrolled a total of 133 patients in two separate cohorts: a clinical discovery cohort (n = 86) and a validation cohort (n = 47)., Results: From 16 validated EV proteins in plasma samples collected from the discovery cohort, only MUC5AC showed significantly higher levels in high-grade lesions. Of the 11 patients with invasive IPMN (inv/HG), 9 had high MUC5AC expression in plasma EV of the 11 patients with high-grade dysplasia alone, only 1 had high MUC5AC expression (sensitivity of 82%, specificity of 100%). These findings were corroborated in a separate validation cohort. The addition of MUC5AC as a biomarker to imaging and high-riskstigmata allowed detection of all cases requiring surgery, whereas imaging and high-risk stigmata alone would have missed 5 of 14 cases (36%)., Conclusions: MUC5AC in circulating EV can predict the presence of invasive carcinoma within IPMN. This approach has the potential to improve the management and follow-up of patients with IPMN including avoiding unnecessary surgery., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aims: Pancreatic ductal adenocarcinomas (PDACs) are increasingly being treated with neoadjuvant therapy. However, the American Joint Committee on Cancer (AJCC) 8th edition T staging based on tumour size does not reflect treatment effect, which often results in multiple, small foci of residual tumour in a background of mass-forming fibrosis. Thus, we evaluated the performance of AJCC 8th edition T staging in predicting patient outcomes by the use of a microscopic tumour size measurement method., Methods and Results: One hundred and six post-neoadjuvant therapy pancreatectomies were reviewed, and all individual tumour foci were measured. T stages based on gross size with microscopic adjustment (GS) and the largest single microscopic focus size (MFS) were examined in association with clinicopathological variables and patient outcomes. Sixty-three of 106 (59%) were locally advanced; 78% received FOLFIRINOX treatment. The average GS and MFS were 25 mm and 11 mm, respectively; nine cases each were classified as T0, 35 and 85 cases as T1, 42 and 12 cases as T2, and 20 and 0 cases as T3, based on the GS and the MFS, respectively. Higher GS-based and MFS-based T stages were significantly associated with higher tumour regression grade, lymphovascular and perineural invasion, and higher N stage. Furthermore, higher MFS-based T stage was significantly associated with shorter disease-free survival (DFS) (P < 0.001) and shorter overall survival (OS) (P = 0.002). GS was significantly associated with OS (P = 0.046), but not with DFS., Conclusions: In post-neoadjuvant therapy PDAC resections, MFS-based T staging is superior to GS-based T staging for predicting patient outcomes, suggesting that microscopic measurements have clinical utility beyond the conventional use of GS measurements alone., (© 2020 John Wiley & Sons Ltd.)

Background: There is limited data on the efficacy of adjuvant therapy (AT) in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMN). This single center retrospective cohort study aims to assess the impact of AT on survival in these patients., Methods: Patients undergoing surgery for invasive IPMN between 1993 and 2018 were included in the study. We compared the clinicopathologic features and evaluated overall survival (OS) using multivariate Cox regression adjusting for adjuvant therapy, age, T and N stage, perineural and lymphovascular invasion. We also assessed survival differences between surgery alone and AT in node negative (N0) and node positive (N+) subgroups., Results: 103 patients were included in the study; 69 underwent surgery alone while 34 also received AT. Patients in the AT group were significantly younger, presented at higher T and N stages and had more perineural and lymphovascular invasion. Median OS in the surgery alone group was 134 months and 65 months in the AT group, p = 0.052. On multivariate analysis, AT was not associated with improved OS; hazard ratio (HR) = 1.03 (0.52-2.05). In N0 patients, compared to surgery alone, AT was associated with a worse median OS (65 vs 167 months, p = 0.03), whereas in N+ patients there was a non-significant improvement (50.5 vs 20.4 months, p = 0.315)., Conclusion: AT did not improve survival in the overall cohort even after multivariate analysis. N0 patients have excellent survival, and AT should probably be avoided in them, whereas it may be considered in patients with N+ disease., Competing Interests: Declaration of competing interest All the authors state that there is no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Background: The risk of pancreatic ductal adenocarcinoma (PDAC) is increased in patients with diabetes mellitus (DM), particularly in those with new-onset DM. However, the impact of DM on outcomes following pancreatic surgery is not fully understood. We sought to explore the effects of DM on post-resection outcomes in patients undergoing either upfront resection or following neoadjuvant treatment (NAT)., Methods: Resections for PDAC between 2007 and 2016 were identified from a prospectively-maintained database. Data on demographics, pathology, and perioperative outcomes were compared between patients with or without DM. Survival analysis was performed using Kaplan-Meier curves and adjusted for confounders by a Cox-proportional hazards model., Results: 662 patients were identified, of whom 277 (41.8%) had DM. Diabetics were more likely to be male, had higher BMI, and higher ASA-scores. At pathology, DM was associated with larger tumors (30 vs. 26 mm; p = 0.041), higher rates of lymph-node involvement (69% vs. 59%; p = 0.031) and perineural invasion (88% vs. 82%; p = 0.026). Despite having similar rates of complications, diabetics experienced higher 30-day mortality (3.2% vs. 0.8%; p = 0.019). Median overall survival was worse in diabetic patients (18 vs. 34 months; p < 0.001); this effect was more pronounced in patients with NAT (18 vs. 54 months; p < 0.001). At multivariate analysis, DM was confirmed as an independent predictor of post-resection survival., Conclusion: DM is a common comorbidity in PDAC and is associated with unfavorable pathology, as well as worse postoperative and oncologic outcomes. The blunted effect on survival is more pronounced in patients who undergo resection following NAT., Competing Interests: Declaration of competing interest All the authors state that there is no conflict of interest., (Copyright © 2019. Published by Elsevier B.V.)

Importance: Chemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood., Objective: To investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy., Design, Setting, and Participants: This prospective study took place in a national referral center for pancreatic diseases in Italy. Consecutive patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma were enrolled at the time of diagnosis (January 2013 through December 2015) and followed up to June 2018., Exposures: The chemotherapy regimen, assigned based on multidisciplinary evaluation, was delivered either at a hub center or at spoke centers. By convention, primary chemotherapy was considered completed after 6 months. After restaging, surgical candidates were selected based on radiologic and biochemical response. All surgeries were carried out at the hub center., Main Outcomes and Measures: Rates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival., Results: Of 680 patients, 267 (39.3%) had borderline resectable and 413 (60.7%) had locally advanced pancreatic ductal adenocarcinoma. Overall, 66 patients (9.7%) were lost to follow-up. The rate of chemotherapy receipt was 92.9% (n = 570). The chemotherapeutic regimens most commonly used included FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) (260 [45.6%]) and gemcitabine plus nanoparticle albumin-bound-paclitaxel (123 [21.6%]). Nineteen patients (3.3%) receiving chemotherapy died within 6 months, mainly for disease progression. The treatment completion rate was 71.6% (408 of 570). The overall rate of resection was 15.1% (93 of 614) (borderline resectable, 60 of 249 [24.1%]; locally advanced, 33 of 365 [9%]; resection:exploration ratio, 63.3%). Independent predictors of resection were age, borderline resectable disease, chemotherapy completion, radiologic response, and biochemical response. The median survival for the whole cohort was 12.8 (95% CI, 11.7-13.9) months. Factors independently associated with survival were completion of chemotherapy, receipt of complementary radiation therapy, and resection. In patients who underwent resection, the median survival was 35.4 (95% CI, 27.0-43.7) months for initially borderline resectable and 41.8 (95% CI, 27.5-56.1) months for initially locally advanced disease. No pretreatment and posttreatment factors were associated with survival after pancreatectomy., Conclusions and Relevance: This pragmatic observational cohort study with an intention-to-treat design provides real-world evidence of outcomes associated with the most current primary chemotherapy regimens used for borderline resectable and locally advanced pancreatic ductal adenocarcinoma.

Background and Aim: Implications of preoperative biliary drain on morbidity and mortality after pancreatoduodenectomy are still controversial. The present study aims to assess the impact of preoperative biliary drain on postoperative outcome and to define optimal serum bilirubin cut-off to recommend biliary drainage in patients undergoing pancreatoduodenectomy., Methods: All consecutive pancreatoduodenectomies carried out at Verona Hospital from 2005 to 2016 were retrospectively analyzed. The study population was divided into three groups: preoperative biliary drained (Stented Group), preoperative jaundice without drainage (Jaundiced Group) and the control group of non-jaundiced, non-stented patients (Control Group)., Results: A total of 1500 patients were included. Seven hundred and fourteen patients (47.6%) received biliary drain (stented group), 258 (17.2%) patients did not (jaundiced group) and 528 (35.2%) patients represented the (control group). Major complications and mortality rates did not differ between groups. Conversely, the risk of developing surgical site infections doubled in the stented group (18.1%) (OR = 2.1, 95% CI = 1.5-2.8). In jaundiced patients, a preoperative bilirubin value greater than 7.5 mg/dL (128 μmol/L) accurately predicted the likelihood of postoperative complications., Conclusion: Preoperative biliary drain does not increase major complications and mortality rates after pancreatoduodenectomy, but it is associated with higher surgical site infection rates. In jaundiced patients, a bilirubin value greater than 7.5 mg/dL (128 μmol/L) should indicate biliary drainage., (© 2018 Japan Gastroenterological Endoscopy Society.)

Background: Despite improvements in the perioperative care, the morbidity rate after pancreaticoduodenectomy (PD) is still higher than 50%. The aim of this study was twofold: first, to assess the correlation between preoperative rectal swab (RS) and intraoperative bile cultures; to examine the impact of RS isolates on postoperative course after PD., Methods: An observational study was conducted analyzing all consecutive PD performed from January 2015 to July 2016. Based on the positivity/negativity of preoperative RS for multi-drug resistant bacteria, two groups of patients were identified (RS+ vs. RS-) and then compared., Results: Three hundred thirty-eight patients were considered for the analysis. RS culture showed a perfect correlation (species and phenotypic antibiotic susceptibility pattern) with bile culture in 157 patients (86.7%). Fifty patients (14.8%) had a RS+. Preoperative biliary drain (PBD) was the single independent preoperative risk factor associated to RS+ (p = 0.021, OR = 2.6, 95% CI = 1.5-11.7). Infective complications (IC) and mortality were independently correlated to RS+ (p = 0.013, OR = 2.9, 95% CI = 1.3-6.7; p = 0.009 OR = 3.4, 95% CI = 1.8-14.9, respectively)., Conclusions: Preoperative surveillance RS-culture's positivity correlates to biliary colonization that occurs after PBD. IC and mortality after PD are associated with RS+. Preoperative RS can direct antibiotic prophylaxis to reduce morbidity and mortality after PD., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Despite improvements in perioperative care, mortality and morbidity rates associated with pancreatic operation still reach 2% and >50%, respectively. Infectious complications after pancreaticoduodenectomy occur in about one-third of the cases. The aim of the study is to define the real burden of infectious complications after pancreaticoduodenectomy and to analyze the risk factors associated with their onset., Methods: Data of consecutive pancreaticoduodenectomies performed at the authors' institution from January 2011 to June 2016 were retrieved from a prospectively maintained database. Based on the presence of infectious complications, the population was separated into 2 groups (infection group positive [IG+] and infection group negative [IG-]) and then compared., Results: During the study period 893 pancreaticoduodenectomies were performed. Overall, infectious complications were detected in 409 out of 893 patients (45.8%). Preoperative biliary drain was the only independent preoperative risk factor for the development of infectious complications (P < .001, odds ratio 3.8). Each complication was found to be statistically more frequent in IG+. In addition, IG+ also had a prolonged hospital stay (P < .020, odds ratio 1.1) and all deaths occurred in this group. The overall multisite infection rate was 41.6%. Multidrug-resistant bacteria were detected in 78.5% of patients. The development of multisite infection was the best predictor of outcome after pancreaticoduodenectomy., Conclusion: The development of postoperative infectious complications is a major determinant of outcome after pancreaticoduodenectomy. In this setting, the reliable negative predictors of the outcome include preoperative biliary drain, site of infection, multidrug-resistant bacteria infections and type of bacteria. Multisite infection was found to be the best predictor of a worse postoperative course after pancreaticoduodenectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: To compare surgical and oncological outcomes after pancreaticoduodenectomy (PD) in patients ≥ 75 years of age with two younger cohorts of patients., Methods: The prospectively maintained Institutional database of pancreatic resection was queried for patients aged ≥ 75 years (late elderly, LE) submitted to PD for any disease from January 2010 to June 2015. We compared clinical, demographic and pathological features and survival outcomes of LE patients with 2 exact matched cohorts of younger patients [≥ 40 to 64 years of age (adults, A) and ≥ 65 to 74 years of age (young elderly, YE)] submitted to PD, according to selected variables., Results: The final LE population, as well as the control groups, were made of 96 subjects. Up to 71% of patients was operated on for a periampullary malignancy and pancreatic cancer (PDAC) accounted for 79% of them. Intraoperative data (estimated blood loss and duration of surgery) did not differ among the groups. The overall complication rate was 65.6%, 61.5% and 58.3% for LE, YE and A patients, respectively, P = NS). Reoperation and cardiovascular complications were significantly more frequent in LE than in YE and A groups ( P = 0.003 and P = 0.019, respectively). When considering either all malignancies and PDAC only, the three groups did not differ in survival. Considering all benign diseases, the estimated mean survival was 58 and 78 mo for ≥ and < 75 years of age (YE + A groups), respectively ( P = 0.012)., Conclusion: Age is not a contraindication for PD. A careful selection of LE patients allows to obtain good surgical and oncological results., Competing Interests: Conflict-of-interest statement: None of the authors have received fees for serving as a speaker or are consultant/advisory board member for any organizations. None of the authors have received research funding from any organizations. None of the authors are employees of any organizations. None of the authors own stocks and/or share in any organizations. None of the authors own patents.