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Importance: Only a few high-volume centers have reported on long-term oncologic outcomes after minimally invasive pancreatic surgery (MIPS) for pancreatic adenocarcinoma, but none of them have shown superior long-term overall survival (OS) compared with open pancreatic surgery (OPS)., Objective: To study long-term survival after MIPS and OPS with curative intent among patients with pancreatic adenocarcinoma., Design, Setting, and Participants: This comparative effectiveness study used a retrospective analysis of a prospectively maintained electronic database of patient data collected between January 2010 and December 2019. Consecutive patients from a high-volume pancreatic cancer referral center were included. Data analysis was conducted from March to October 2022. Median follow-up time was 56.8 months., Exposures: Patients were matched using propensity score models to study long-term survival., Main Outcomes and Measures: Survival outcomes were analyzed using the Cox proportional hazards model. Variables used for propensity score correction were TNM stage, tumor dimension, lymph node status, type of operation, simultaneous vascular resection, neoadjuvant chemotherapy, adjuvant chemotherapy, sex, age, and American Society of Anesthesiologists score. Additional corrections were made for year of surgery and type of adjuvant chemotherapy., Results: After propensity score matching the sample of 396 patients, there were 198 patients in the MIPS group (89 [44.9%] men; median [range] age, 68 [32-87] years) and 198 in the OPS group (94 [47.5%] men; median [range] age, 67 [39-84] years). Median OS in the MIPS group was 30.7 (95% CI, 26.2-36.8) months compared with 20.3 (95% CI, 17.6-23.5) months after OPS (hazard ratio [HR], 0.70; 95% CI, 0.56-0.87; P = .002). Median disease-free survival (DFS) after MIPS vs OPS was 14.8 (95% CI, 11.8-17.0) months vs 10.7 (95% CI, 9.0-12.1) months (HR, 0.71; 95% CI, 0.57-0.89; P = .003). Additional corrections for year of surgery and type of adjuvant chemotherapy showed better OS (year of surgery: HR, 0.74; 95% CI, 0.57-0.96; P = .02; adjuvant chemotherapy: HR, 0.71; 95% CI, 0.56-0.90; P = .005) and DFS (year of surgery: HR, 0.77; 95% CI, 0.59-0.99; P = .04; adjuvant chemotherapy: HR, 0.72; 95% CI, 0.57-0.92; P = .009) for patients undergoing minimally invasive vs open surgery., Conclusions and Relevance: In this study of 396 patients with borderline resectable and resectable pancreatic adenocarcinoma, MIPS was associated with better OS and DFS than OPS. Centralization of MIPS should be stimulated, and pancreatic surgeons should be encouraged to pass the learning curve before implementing MIPS for pancreatic adenocarcinoma in daily clinical practice.

Background and study aims  Biliary stenting of unresectable malignant bile duct obstruction is generally accepted as the standard of care but it can be hampered by tumor ingrowth and stent dysfunction. We aimed to test the feasibility, safety, and biliary patency rate of a new endoscopically applied intraductal radiofrequency ablation (RFA) device. Patients and methods  Eighteen patients with inoperable malignant biliary obstruction underwent endoscopic retrograde cholangiopancreatography (ERCP)-directed RFA and stenting. Results  Between December 2014 and November 2015, 18 patients underwent RFA to the intended region, with no complications within 3 months of the procedure. Bilirubin levels post-RFA and stenting decreased significantly (7.8 ± 1 mg/dL to 1.7 ± 0.4 mg/dL; P  < 0.001). At 90 and 180 days post-intervention, biliary patency was maintained in 80 % and 69 % of patients still alive at that time, respectively. The median overall stent patency was 110 days (range 16 - 374), with a median patient survival of 227 days (range 16 - 374). Conclusion  Intraductal RFA using a new device in patients with inoperable biliopancreatic cancer complicated by jaundice appeared feasible and safe with acceptable biliary patency. Randomized trials with prolonged follow-up are warranted.ClinTrials.gov: NCT02468076., Competing Interests: Competing interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Postoperative pancreatic fistula is the leading cause of death and morbidity after pancreaticoduodenectomy. However, the best reconstruction method to reduce occurrence of fistula is debated. We did a multicentre, randomised superiority trial to compare the outcomes of different reconstructive techniques in patients undergoing pancreaticoduodenectomy for pancreatic or periampullary tumours., Methods: Patients aged 18-85 years with confirmed or suspected neoplasms of the pancreas, distal bile duct, ampulla vateri, duodenum, or periampullary tumours were eligible for inclusion. An internet-based platform was used to randomly assign patients to either pancreaticojejunostomy or pancreaticogastrostomy as reconstruction after pancreaticoduodenectomy, using permuted blocks with six patients per block. Within each centre the randomisation was stratified on the pancreatic duct diameter (≤3 mm vs >3 mm) measured at the time of surgery. The primary endpoint was the occurrence of clinical postoperative pancreatic fistula (grade B or C) as defined by the International Study Group on Pancreatic Fistula. The study was not masked and analyses were done by intention to treat. Patient follow-up was closed 2 months after discharge from the hospital. This study is registered with ClinicalTrials.gov, number NCT00830778., Findings: Between June, 2009, and August, 2012, we randomly allocated 167 patients to receive pancreaticojejunostomy and 162 to receive pancreaticogastrostomy. 33 (19.8%) patients in the pancreaticojejunostomy group and 13 (8.0%) in the pancreaticogastrostomy group had clinical postoperative pancreatic fistula (OR 2.86, 95% CI 1.38-6.17; p=0.002). The overall incidence of postoperative complications did not differ significantly between the groups (99 in the pancreaticojejunostomy group vs 100 in the pancreaticogastrostomy group), although more events in the pancreaticojejunostomy group were of grade ≥3a than in the pancreaticogastrostomy group (39 vs 35)., Interpretation: In patients undergoing pancreaticoduodenectomy for pancreatic head or periampullary tumours, pancreaticogastrostomy is more efficient than pancreaticojejunostomy in reducing the incidence of postoperative pancreatic fistula., Funding: Funding Johnson & Johnson Medical Devices, Belgium., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Epithelial cell adhesion molecule (EpCAM) has been used as surrogate marker for the quantification of circulating tumour cells (CTC). Our aim was to prospectively study the value of a real-time RT-PCR assay for EpCAM detection in the peripheral blood and peritoneal cavity of patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC)., Methods: From 48 patients with PDAC (40 resectable, 8 unresectable) and 10 patients with chronic pancreatitis undergoing pancreatectomy 10 ml of venous blood was drawn preoperatively (PB) and postoperatively (POB, day 1 (D1B), day 7 (D7B) and after 6 weeks (6WB). Of all patients undergoing pancreatectomy, 40 ml peritoneal lavage fluid was taken preoperatively and postoperatively. A real-time RT-PCR assay (TaqMan, ABI Prism 7700) was developed for the detection of EpCAM mRNA. To discriminate between EpCAM-positive and negative samples a cut-off was applied. Median postoperative follow-up was 24.0 months (range: 0.7-41.3)., Results: PB was EpCAM-positive+ in 25% of patients versus 65% of patients in POB (p < 0.0001). EpCAM+ was noted at D1B, D7B and 6WB was found in 28.6%, 23.1% and 23.5% of patients respectively. Preoperative peritoneal lavage fluid was EpCAM+ in 10.3% versus 53.8% of patients postoperatively (p < 0.0001). At none of the time-points, an association was found between EpCAM positivity in blood and/or peritoneal cavity and cancer-specific or disease-free survival. Also, no significant associations were found between clinicopathological variables and perioperative EpCAM positivity., Conclusions: Despite a significant increase in EpCAM counts in postoperative blood and peritoneal lavage fluid this was not associated with worse prognosis after pancreatectomy for PDAC., Trial Registration: Clinicaltrials.gov NCT00495924.

Background: In several malignancies extracapsular lymph node involvement (ECLNI) identifies a subgroup of patients with worse prognosis but no data are available on its significance in pancreatic ductal adenocarcinoma (PDAC). The aim of our study was to assess the prognostic relevance of ECLNI in resectable PDAC., Methods: A retrospective analysis was performed of 137 consecutive pancreatic resections for PDAC. Two investigators blinded for survival data systematically reviewed all pathological data. Survival curves were estimated using the Kaplan-Meier method. Multivariable Cox regression models were used to identify predictors of disease-free survival (DFS) and overall survival (OS). The median follow-up after surgery was 19 months., Results: ECLNI was identified in 59 of 99 node-positive patients. The median DFS in patients with ECLNI vs. intracapsular LNI (ICLNI) was 6.8 vs. 12.0 months, respectively (P=.027). The median OS in patients with ECLNI vs. ICLNI was 16.1 and 21.8 months, respectively (P=.098). On multivariable analysis extracapsular lymph node ratio (ECLNR) was identified as an independent predictor of OS (P=.003). In patients with ECLNI, both OS and DFS were improved after adjuvant chemoradiation compared with those who did not receive adjuvant treatment (P=.01)., Conclusions: Extracapsular lymph node ratio is an independent predictor of survival in patients with PDAC. Patients with ECLNI from pancreatic cancer seem to benefit from adjuvant chemoradiation but not from chemotherapy alone.

Background: The primary objective of this study was to determine the maximum tolerated dose (MTD) of escalating doses of radiotherapy (RT) concomitantly with a fixed dose of gemcitabine (300 mg/m2/week) within the same overall treatment time., Methods: Thirteen patients were included. Gemcitabine 300 mg/m2/week was administered prior to RT. The initial dose of RT was 45 Gy in 1.8 Gy fractions, escalated by adding 5 fractions of 1.8 Gy (one/week) to a dose of 54 Gy with a total duration kept at 5 weeks. All patients received a dynamic MRI to assess the pancreatic respiratory related movements. Toxicity was scored using the RTOG-EORTC toxicity criteria., Results: Three of six patients experienced an acute dose limiting toxicity (DLT) at the 54 Gy dose level. For these patients a grade III gastro-intestinal toxicity (GI) was noted. Patients treated at the 45 Gy dose level tolerated therapy without DLT. The 54 Gy dose level was designated as the MTD and was deemed not suitable for further investigation. Between both dose levels, there was a significant difference in percentage weight loss (p = 0.006) and also in cumulative GI toxicity (p = 0.027). There was no grade 3 toxicity in the 45 Gy cohort versus 4 grade 3 toxicity events in the 54 Gy cohort. The mean dose to the duodenum was significantly higher in the 54 Gy cohort (38.45 Gy vs. 51.82 Gy; p = 0.001)., Conclusion: Accelerated dose escalation to a total dose of 54 Gy with 300 mg/m2/week gemcitabine was not feasible. GI toxicity was the DLT. Retrospectively, the dose escalation of 9 Gy by accelerated radiotherapy might have been to large. A dose of 45 Gy is recommended. Considering the good patient outcomes, there might be a role for the investigation of a fixed dose of gemcitabine and concurrent RT with small fractions (1.8 Gy/day) in borderline resectable or unresectable non-metastatic locally advanced pancreatic cancer.

Patients with pancreatic cancer have a poor prognosis although systemic treatment has slightly improved the outcome for those with advanced pancreatic cancer, The approach to a patient with pancreatic cancer remains a great challenge. Patients often present with advanced disease and many are already in poor general condition at the time of diagnosis. Today, surgery remains the only curative therapeutic option. A small number of pancreatic adenocarcinomas, however, are resectable and relapses after surgery are very frequent. The reference treatment in patients with metastatic pancreatic cancer is gemcitabine. The median survival of patients with advanced pancreatic cancer who are treated with gemcitabine is approximately 6 months and only approximately 20% of patients will be alive at 1 year. Combinations of gemcitabine with new cytotoxic agents and with novel targeted agents hold the promise for improving the outcome. Randomized phase III studies are, however, still ongoing. Since most patients will relapse after complete surgical resection of pancreatic cancer, a search for a better adjuvant or neoadjuvant treatment is important. Although several randomized studies have suggested an improved outcome for a postoperative chemoradiotherapy or chemotherapy, the role of an adjuvant treatment remains today controversial. Randomized phase III studies are ongoing. A neoadjuvant strategy might therefore also play a role, but phase III studies are lacking. The systematic evaluation of new drugs in well designed clinical trials and the search for new molecular targets for treatment are crucial in our aim to improve the outcome for patients with pancreatic cancer.