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Background: Difficulty scoring systems are important for the safe, stepwise implementation of new procedures. We designed a retrospective observational study for building a difficulty score for robotic pancreatoduodenectomy. Methods: The difficulty score (PD-ROBOSCORE) aims at predicting severe postoperative complications after robotic pancreatoduodenectomy. The PD-ROBOSCORE was developed in a training cohort of 198 robotic pancreatoduodenectomies and was validated in an international multicenter cohort of 686 robotic pancreatoduodenectomies. Finally, all centers tested the model during the early learning curve (n = 300). Growing difficulty levels (low, intermediate, high) were defined using cut-off values set at the 33rd and 66th percentile (NCT04662346). Results: Factors included in the final multivariate model were a body mass index of ≥25 kg/m2 for males and ≥30 kg/m2 for females (odds ratio:2.39; P < .0001), borderline resectable tumor (odd ratio:1.98; P < .0001), uncinate process tumor (odds ratio:1.69; P < .0001), pancreatic duct size

Contains fulltext : 291891.pdf (Publisher’s version ) (Closed access) BACKGROUND: The International Study Group of Pancreatic Surgery 4-tier (ie, A-D) risk classification for postoperative pancreatic fistula grade B/C is based on pancreatic texture and pancreatic duct size: A (not-soft texture and pancreatic duct >3 mm), B (not-soft texture and pancreatic duct ≤3 mm), C (soft texture and pancreatic duct >3 mm), and D (soft texture and pancreatic duct ≤3 mm). This study aimed to validate the International Study Group of Pancreatic Surgery risk classification for postoperative pancreatic fistula after pancreatoduodenectomy. METHODS: Consecutive patients after pancreatoduodenectomy for all indications (2014-2021) were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. The rate of postoperative pancreatic fistula grade B/C (according to the International Study Group of Pancreatic Surgery 2016 definition) was calculated per risk category. Model performance was assessed using the area under the receiver operating curve (discrimination) and calibration plots. RESULTS: Overall, 3,900 patients were included in risk categories: A (n = 1,046), B (n = 498), C (n = 963), and D (n = 1,393) with corresponding postoperative pancreatic fistula grade B/C rates of 3.8%, 12.2%, 15.6%, and 29.6%. Per category, the in-hospital mortality rates were 1.3%, 3.4%, 2.9%, and 4.1%, P = .001. There was no difference in the rate of postoperative pancreatic fistula between risk categories B and C (12.2% vs 15.6%, P = .101). When simplifying the classification system to a 3-tier classification system (based on 0, 1, and 2 risk factors), the discrimination was not significantly different (area under the receiver operating curve 0.697 vs area under the receiver operating curve 0.701, P = .077). CONCLUSION: This validation of the 4-tier International Study Group of Pancreatic Surgery risk classification for postoperative pancreatic fistula after pancreatoduodenectomy confirmed its predictive value. However, as the 2 middle risk categories provide no added predictive value, a simplified 3-tier classification with comparable predictive value is proposed and should be validated in future prospective studies.

Background: For logistical reasons, some high-volume centers have developed surgical programs wherein 1 surgical team performs 2 pancreatoduodenectomies on a single day. It is unclear whether this practice has a negative impact on surgical outcome. Methods: We conuducted a retrospective analysis including all consecutive open pancreatoduodenectomies in a single high-volume center (2014–2021). Pancreatoduodenectomies were grouped as the first (pancreatoduodenectomy-1) or second (pancreatoduodenectomy-2) pancreatoduodenectomy on a single day (ie, paired pancreatoduodenectomies) and as pancreatoduodenectomy-3 whenever 1 pancreatoduodenectomy was performed per day (ie, unpaired). Patients undergoing minimally invasive procedures were excluded. The primary outcomes were major morbidity (ie, Clavien-Dindo grade ≥IIIa) and mortality. Results: Among 689 patients, 151 patients had undergone minimally invasive pancreatoduodenectomy, leaving 538 patients after open pancreatoduodenectomy for inclusion. The overall rate of major morbidity was 37.4% (n = 200/538) and in-hospital/30-day mortality 1.7% (n = 9/538). Overall, 136 (25.3%) patients were operated in 68 pancreatoduodenectomy-1/ pancreatoduodenectomy-2 pairs and 402 (74.7%) patients as unpaired pancreatoduodenectomy (pancreatoduodenectomy-3). No differences were found between pancreatoduodenectomy-1 and pancreatoduodenectomy-2 regarding the rates of major morbidity (35.3% vs 26.5%; P = .265) and mortality (1.5% vs 0%; P = .999). Between the 68 pancreatoduodenectomy-1/ pancreatoduodenectomy-2 pairs and the 402 unpaired pancreatoduodenectomies, the rates of major morbidity (30.9% vs 39.6%; P = .071) and mortality (0.7% vs 2.0%; P = .461) did not differ significantly. In multivariable logistic regression analysis, pancreatoduodenectomy-1 was not associated with major morbidity (odds ratio = 0.913 [95% confidence interval 0.515–1.620]; P = .756), whereas pancreatoduodenectomy-2 was associated with less major morbidity (odds ratio = 0.522 [95% confidence interval 0.277–0.983]; P = .045). Conclusion: In a high-volume setting, performing 2 consecutive open pancreatoduodenectomies on a single operating day appears to be safe. This approach may be an option when logistically required.

Background: Follow-up in patients with intraductal papillary mucinous neoplasm (IPMN) aims to detect advanced neoplasia (high-grade dysplasia/cancer) in an early stage. The 2015 American Gastroenterological Association (AGA), 2017 International Association of Pancreatology (IAP), and the 2018 European Study Group on Cystic tumours of the Pancreas (European) guidelines differ in their recommendations on indications for surgery. However, it remains unclear which guideline is most accurate in predicting advanced neoplasia in IPMN. Methods: Patients who underwent surgery were extracted from a prospective database (January 2006–January 2021). In patients with IPMN, final pathology was compared with the indication for surgery according to the guidelines. ROC-curves were calculated to determine the diagnostic accuracy for each guideline. Results: Overall, 247 patients underwent surgery for cystic lesions. In 145 patients with IPMN, 52 had advanced neoplasia, of which the AGA guideline would have advised surgery in 14 (27%), the IAP and European guideline in 49 (94%) and 50 (96%). In 93 patients without advanced neoplasia, the AGA, IAP, and European guidelines would incorrectly have advised surgery in 8 (8.6%), 77 (83%) and 71 (76%). Conclusion: The European and IAP guidelines are clearly superior in detecting advanced neoplasia in IPMN as compared to the AGA, albeit at the cost of a higher rate of unnecessary surgery. To harmonize care and to avoid confusion caused by conflicting statements, a global evidence-based guideline for PCN in collaboration with the various guidelines groups is required once the current guidelines require an update.

Glucose control in patients after total pancreatectomy is problematic because of the complete absence of α- and β-cells, leading to impaired quality of life. A novel, bihormonal artificial pancreas (BIHAP), using both insulin and glucagon, may improve glucose control, but studies in this setting are lacking.To assess the efficacy and safety of the BIHAP in patients after total pancreatectomy.This randomized crossover clinical trial compared the fully closed-loop BIHAP with current diabetes care (ie, insulin pump or pen therapy) in 12 adult outpatients after total pancreatectomy. Patients were recruited between August 21 and November 16, 2020. This first-in-patient study began with a feasibility phase in 2 patients. Subsequently, 12 patients were randomly assigned to 7-day treatment with the BIHAP (preceded by a 5-day training period) followed by 7-day treatment with current diabetes care, or the same treatments in reverse order. Statistical analysis was by Wilcoxon signed rank and Mann-Whitney U tests, with significance set at a 2-sided P.05.The primary outcome was the percentage of time spent in euglycemia (70-180 mg/dL [3.9-10 mmol/L]) as assessed by continuous glucose monitoring.In total, 12 patients (7 men and 3 women; median [IQR] age, 62.5 [43.1-74.0] years) were randomly assigned, of whom 3 did not complete the BIHAP phase and 1 was replaced. The time spent in euglycemia was significantly higher during treatment with the BIHAP (median, 78.30%; IQR, 71.05%-82.61%) than current diabetes care (median, 57.38%; IQR, 52.38%-81.35%; P = .03). In addition, the time spent in hypoglycemia (70 mg/dL [3.9 mmol/L]) was lower with the BIHAP (median, 0.00% [IQR, 0.00%-0.07%] vs 1.61% [IQR, 0.80%-3.81%]; P = .004). No serious adverse events occurred.Patients using the BIHAP after total pancreatectomy experienced an increased percentage of time in euglycemia and a reduced percentage of time in hypoglycemia compared with current diabetes care, without apparent safety risks. Larger randomized trials, including longer periods of treatment and an assessment of quality of life, should confirm these findings.trialregister.nl Identifier: NL8871.

Background: In patients with familial adenomatous polyposis (FAP), extensive nonmalignant duodenal polyposis not amenable to endoscopic management demands surgical resection for which pancreas-preserving total duodenectomy (PPTD) offers a pancreatic parenchyma sparing approach. Methods: This is a retrospective cohort study including consecutive patients who underwent PPTD for FAP. Reconstruction involved a Billroth II anastomosis with a short isolated jejunal limb to facilitate future endoscopic surveillance. Short and long-term outcomes were evaluated. Results: Overall, 30 patients underwent PPTD for Spigelman stage III (n = 6) or IV (n = 24). Sixteen patients experienced a severe complication (Clavien–Dindo grade III/IV) including postoperative pancreatic fistula (ISGPS grade B/C) in twelve. There was no all cause in-hospital and 90-day mortality. During follow-up (median 125 months), five patients developed acute pancreatitis, one new-onset diabetes and one exocrine pancreatic insufficiency. During endoscopic surveillance in 27 patients, jejunal adenomas were detected in 22 and advanced adenomas in 11. An additional surgical resection was required in four patients with extensive jejunal polyposis. None developed jejunal cancer. The 10-year overall survival rate was 93.3%. Conclusion: Postoperative morbidity after PPTD is substantial but on the long-term, rates of pancreatic insufficiencies are low. Most patients develop jejunal adenomas at follow-up, highlighting the need for endoscopic surveillance.

Liver regeneration is crucial to restore the functional liver mass after liver resection. The aim of this study was to evaluate the early postoperative changes in remnant liver function, volume and liver stiffness after major liver resection and their correlation with postoperative outcomes.Patients undergoing major liver resection (≥3 segments) between February and November 2018 underwent both functional assessment using technetium-99m mebrofenin hepatobiliary scintigraphy (HBS) and CT-volumetry of the (future) remnant liver on preoperative day 1, the 5A total of 18 patients were included of whom 10 (56%) had severe complications and one patient (5%) developed liver failure. Function and volume of the remnant liver had increased by the 5Functional regeneration of the remnant liver predominantly occurs during the first 5 days after resection. In case of severe complications, functional regeneration is delayed, in contrast to volume increase.

Background The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator. Methods This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014–2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated. Results In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P < 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P < 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (−1.71 (95 per cent c.i. −2.27 to −1.05) and −3.05 (95 per cent c.i. −4.03 to −1.80) respectively) and overall survival (−1.92 (95 per cent c.i. −2.60 to −1.16) and −3.49 (95 per cent c.i. −4.84 to −2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (−5.38 (95 per cent c.i. −9.27 to −1.94)) and overall survival (−6.32 (95 per cent c.i. −10.43 to −1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy. Conclusion Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate treatment of complications and use of neoadjuvant treatment may improve oncological outcomes.

Background The management of pancreatic body and tail lesions is underexposed. It remains unclear whether endoscopic ultrasonography (EUS) increases the accuracy of the preoperative workup. This study assessed the diagnostic value and safety of EUS in addition to cross-sectional imaging in a surgical cohort of patients with pancreatic body or tail lesions. Methods A multicenter retrospective cohort study was performed of patients who underwent distal pancreatectomy from 2010 to 2017. The composite primary outcome was the additional value of EUS, defined as: (a) EUS confirmed an uncertain diagnosis on cross-sectional imaging, (b) EUS was correct in case of discrepancy with cross-sectional imaging, or (c) EUS provided tissue diagnosis for neoadjuvant treatment. Furthermore, serious adverse events and needle tract seeding were assessed. Results In total, 181 patients were included, of whom 123 (68%) underwent EUS besides cross-sectional imaging. Postoperative pathology was heterogeneous: 91 was malignant, 49 premalignant, 41 benign. Most lesions were solid (n = 117). EUS had additional value in 59/123 (48%) patients; 27/50 (54%) of cystic and 32/73 (44%) of solid lesions. No serious adverse event or needle tract seeding following EUS occurred. Conclusion EUS had additional value besides cross-sectional imaging in half of the patients and showed low associated risks.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma, the main cellular constituents of which are cancer-associated fibroblasts (CAFs). Stroma-targeting agents have been proposed to improve the poor outcome of current treatments. However, clinical trials using these agents showed disappointing results. Heterogeneity in the PDAC CAF population was recently delineated demonstrating that both tumor-promoting and tumor-suppressive activities co-exist in the stroma. Here, we aimed to identify biomarkers for the CAF population that contribute to a favorable outcome. RNA-sequencing reads from patient-derived xenografts (PDXs) were mapped to the human and mouse genome to allocate the expression of genes to the tumor or stroma. Survival meta-analysis for stromal genes was performed and applied to human protein atlas data to identify circulating biomarkers. The candidate protein was perturbed in co-cultures and assessed in existing and novel single-cell gene expression analysis from control, pancreatitis, pancreatitis-recovered and PDAC mouse models. Serum levels of the candidate biomarker were measured in two independent cohorts totaling 148 PDAC patients and related them to overall survival. Osteoglycin (OGN) was identified as a candidate serum prognostic marker. Single-cell analysis indicated that Ogn is derived from a subgroup of inflammatory CAFs. Ogn-expressing fibroblasts are distinct from resident healthy pancreatic stellate cells and arise during pancreatitis. Serum OGN levels were prognostic for favorable overall survival in two independent PDAC cohorts (HR = 0.47, P = .042 and HR = 0.53, P = .006). Altogether, we conclude that high circulating OGN levels inform on a previously unrecognized subgroup of CAFs and predict favorable outcomes in resectable PDAC.

Background and Aims: In high-risk individuals (HRIs), we aimed to assess the cumulative incidence of intraductal papillary mucinous neoplasms (IPMNs) and compare IPMN growth, neoplastic progression rate, and the value of growth as predictor for neoplastic progression to these in sporadic IPMNs. Methods: We performed annual surveillance of Dutch HRIs, involving carriers of germline pathogenic variants (PVs) and PV-negative familial pancreatic cancer kindreds. HRIs with IPMNs were compared with Italian individuals without familial risk under surveillance for sporadic IPMNs. Results: A total of 457 HRIs were followed for 48 (range 2–172) months; the estimated cumulative IPMN incidence was 46% (95% confidence interval, 28%–64%). In comparison with 442 control individuals, IPMNs in HRIs were more likely to grow ≥2.5 mm/y (31% vs 7%; P < .001) and develop worrisome features (32% vs 19%; P = .010). PV carriers with IPMNs more often displayed neoplastic progression (n = 3 [11%] vs n = 6 [1%]; P = .011), while familial pancreatic cancer kindreds did not (n = 0 [0%]; P = 1.000). The malignancy risk in a PV carrier with an IPMN was 23% for growth rates ≥2.5 mm/y (n = 13), 30% for ≥5 mm/y (n = 10), and 60% for ≥10 mm/y (n = 5). Conclusions: The cumulative incidence of IPMNs in HRIs is higher than previously reported in the general population. Compared with sporadic IPMNs, they have an increased growth rate. PV carriers with IPMNs are suggested to be at a higher malignancy risk. Intensive follow-up should be considered for PV carriers with an IPMN growing ≥2.5 mm/y, and surgical resection for those growing ≥5 mm/y.

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in this study. We conducted a multi-phase study analysing 7,745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14,666 PDAC cases and 221,897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR=1.11, 95%CI=1.07-1.15, P=5.25×10-9 ). CDKN2B-AS1/ANRIL is a long non-coding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases. This article is protected by copyright. All rights reserved.

BACKGROUND: The necessity of the staging laparoscopy in patients with pancreatic cancer is still debated. The objective of this study was to assess the yield of staging laparoscopy for detecting occult metastases in patients with resectable or borderline resectable pancreatic cancer.METHOD: This was a post-hoc analysis of the randomized controlled PREOPANC trial in which patients with resectable or borderline resectable pancreatic cancer were randomized between preoperative chemoradiotherapy or immediate surgery. Patients assigned to preoperative treatment underwent a staging laparoscopy prior to preoperative treatment according to protocol, to avoid unnecessary chemoradiotherapy in patients with occult metastatic disease.RESULTS: Of the 246 included patients, 7 did not undergo surgery. A staging laparoscopy was performed in 133 patients (55.6%) and explorative laparotomy in 106 patients (44.4%). At staging laparoscopy, occult metastases were detected in 13 patients (9.8%); 12 liver metastases and 1 peritoneal metastasis. At direct explorative laparotomy, occult metastases were found in 9 patients (8.5%); 6 with liver metastases, 1 with peritoneal metastases, and 2 with metastases at multiple sites. One patient had peritoneal metastases at exploration after a negative staging laparoscopy. Patients with occult metastases were more likely to receive palliative chemotherapy if found with staging laparoscopy compared to laparotomy (76.9% vs. 30.0%, p = 0.040).CONCLUSIONS: Staging laparoscopy detected occult metastases in about 10% of patients with resectable or borderline resectable pancreatic cancer. These patients were more likely to receive palliative systemic chemotherapy compared to patients in whom occult metastases were detected with laparotomy. A staging laparoscopy is recommended before planned resection.

Contains fulltext : 251531.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. SUMMARY OF BACKGROUND DATA: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives. METHODS: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely. RESULTS: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay [PAF 27.6% (95% CI 23.5-31.8)]. The impact of individual complications on unplanned readmission was smaller than 11%. CONCLUSION: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying.

Background Delayed gastric emptying (DGE) is one of the most common complications following pancreatoduodenectomy (PD). In-hospital costs of DGE are unknown as well as the financial headroom for novel prophylactic treatments. This retrospective study aims to estimate the hospital costs of DGE and model the financial headroom per patient for new prophylactic treatment strategies within budget. Methods Retrospective analysis of a single-center prospective database including patients after PD (2010–2017). In-hospital costs for clinically relevant DGE (ISGPS grade B/C) were calculated by comparing patient groups with and without DGE or other complications. The financial headroom per patient was modelled for potential reductions (0–100%) of empirical DGE baseline risks (15–30%). Results Overall, DGE was present in 156 (26.9%) of 581 patients after PD. Costs for patients with isolated DGE (n = 90) were €10,295 higher than for patients without complications (n = 333). Costs for patients with other complications including DGE (n = 66) were €9008 higher than for patients with other complications without DGE (n = 92). The financial headroom for a novel prophylactic treatment per patient undergoing PD was €975 per 10% absolute decrease of DGE risk. Conclusion Hospital costs of DGE after PD are substantial. The financial headroom per patient for new DGE prophylactic treatments can be easily calculated via www.pancreascalculator.com.

BACKGROUND: The aim of this study was to investigate the incidence and risk factors of primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma.METHODS: All patients who underwent a major liver resection for presumed perihilar cholangiocarcinoma between 2000 and 2020 at 2 tertiary-referral hospitals were included. Liver failure was defined according to the International Study Group for Liver Surgery criteria, and only grade B/C was considered clinically relevant. Primary liver failure was defined as failure without any underlying postoperative cause, and secondary liver failure was defined as liver failure with an onset after an underlying postoperative complication as a cause.RESULTS: The incidence of liver failure and 90-day mortality were 20.9% and 17.0% in the 253 included patients, respectively. The incidences of primary liver failure was 9.1% and secondary liver failure was 11.9%. Abdominal sepsis, portal vein thrombosis, and arterial thrombosis were the most frequent causes. The absence of preoperative remnant liver assessment and blood loss were independent risk factors for primary liver failure. Independent risk factors for secondary liver failure were Eastern Cooperative Oncology group performance status, percutaneous biliary drainage, and preoperative cholangitis.CONCLUSION: Liver failure after major liver resection for perihilar cholangiocarcinoma occurred in 1 of every 5 patients. The proposed subdivision into primary and secondary liver failure could help to understand differences in outcomes between centers and help to reduce liver failure.

Background: Total pancreatectomy has high morbidity and mortality and differences among countries are currently unknown. This study compared the use and postoperative outcomes of total pancreatec-tomy among 4 Western countries. Methods: Patients who underwent one-stage total pancreatectomy were included from registries in the United States, Germany, the Netherlands, and Sweden (2014-2018). Use of total pancreatectomy was assessed by calculating the ratio total pancreatectomy to pancreatoduodenectomy. Primary outcomes were major morbidity (Clavien Dindo >3) and in-hospital mortality. Predictors for the primary outcomes were assessed in multivariable logistic regression analyses. Sensitivity analysis assessed the impact of volume (low-volume 40 pancreatoduodenectomies annually; data available for the Netherlands and Germany). Results: In total, 1,579 patients underwent one-stage total pancreatectomy. The relative use of total pancreatectomy to pancreatoduodenectomy varied up to fivefold (United States 0.03, Germany 0.15, the Netherlands 0.03, and Sweden 0.15; P < .001). Both the indication and several baseline characteristics differed significantly among countries. Major morbidity occurred in 423 patients (26.8%) and differed (22.3%, 34.9%, 38.3%, and 15.9%, respectively; P < .001). In-hospital mortality occurred in 85 patients (5.4%) and also differed (1.8%, 10.2%, 10.8%, 1.9%, respectively; P < .001). Country, age >75, and vascular resection were predictors for in-hospital mortality. In-hospital mortality was lower in high-volume centers in the Netherlands (4.9% vs 23.1%; P = .002), but not in Germany (9.8% vs 10.6%; P = .733). Conclusion: Considerable differences in the use of total pancreatectomy, patient characteristics, and postoperative outcome were noted among 4 Western countries with better outcomes in the United States and Sweden. These large, yet unexplained, differences require further research to ultimately improve patient outcome. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BACKGROUND: The aim of this study was to determine pancreatic surgery specific short- and long-term complications of pediatric, adolescent and young adult (PAYA) patients who underwent pancreatic resection, as compared to a comparator cohort of adults.METHODS: A nationwide retrospective cohort study was performed in PAYA patients who underwent pancreatic resection between 2007 and 2016. PAYA was defined as all patients RESULTS: A total of 230 patients were included in the PAYA cohort (112 distal pancreatectomies, 99 pancreatoduodenectomies), and 2526 patients in the comparator cohort. For pancreatoduodenectomy, severe morbidity (29.3% vs. 28.6%; P = 0.881), in-hospital mortality (1% vs. 4%; P = 0.179) and textbook outcome (62% vs. 58%; P = 0.572) were comparable between the PAYA and the comparator cohort. These outcomes were also similar for distal pancreatectomy. After pancreatoduodenectomy, new-onset diabetes mellitus (8% vs. 16%) and exocrine pancreatic insufficiency (27% vs. 73%) were lower in the PAYA cohort when compared to adult literature.CONCLUSION: Pancreatic surgery-specific complications were comparable with patients ≥40 years. Development of endocrine and exocrine insufficiency in PAYA patients who underwent pancreatoduodenectomy, however, was substantially lower compared to adult literature.

OBJECTIVE: To describe outcome after pancreatic surgery in the first six years of a mandatory nationwide audit. BACKGROUND: Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. METHODS: This nationwide cohort study included consecutive patients after pancreatoduodenectomy and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between three time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue and in-hospital mortality. RESULTS: Overall, 5345 patients were included, of whom 4227 after pancreatoduodenectomy and 1118 after distal pancreatectomy. After pancreatoduodenectomy, failure to rescue improved from 13% to 7.4% (OR 0.64, 95%CI 0.50-0.80, P75 years (18% to 22%, P=0.006), ASA score ≥3 (19% to 31%, P

Robotic pancreatoduodenectomy (RPD) for pancreatic cancer is a challenging procedure. Aberrant vasculature may increase the technical difficulty. Several studies have described the safety of RPD in case of a replaced or aberrant right hepatic artery, but detailed video descriptions of the approach are lacking. This case report describes a step--by--step technical video in case of a replaced right hepatic artery. A 58-year-old woman presented with an incidental finding of a 1.7 cm pancreatic head mass. RPD was performed using the da Vinci Xi system and involves a robotic-assisted pancreatico- and hepatico-jejunostomy and open gastro-jejunostomy at the specimen extraction site. The operation time was 410 min with 220 mL of blood loss. The patient had an uncomplicated postoperative course and was discharged after 5 days. Pathology revealed a pancreatic head cancer. RPD is a feasible and safe procedure in case of a replaced hepatic artery when performed in selected patients in high-volume centers by experienced surgeons.

The aim of this study was to assess the clinical impact and risk factors of chyle leak (CL).In 2017, the International Study Group for Pancreatic Surgery (ISGPS) published the consensus definition of CL. Multicenter series validating this definition are lacking and previous studies investigating risk factors have used different definitions and showed heterogeneous results.This observational cohort study included all consecutive patients after pancreatoduodenectomy in all 19 centers in the mandatory nationwide Dutch Pancreatic Cancer Audit (2017-2019). The primary endpoint was CL (ISGPS grade B/C). Multivariable logistic regression analyses were performed.Overall, 2159 patients after pancreatoduodenectomy were included. The rate of CL was 7.0% (n=152), including 6.9% (n=150) grade B and 0.1% (n=2) grade C. CL was independently associated with a prolonged hospital stay [odds ratio (OR)=2.84, 95% confidence interval (CI): 1.85-4.36, P0.001] but not with mortality (OR=0.3, 95% CI: 0.0-2.3, P=0.244). In multivariable analyses, independent predictors for CL were vascular resection (OR=2.1, 95% CI: 1.4-3.2, P0.001) and open surgery (OR=3.5, 95% CI: 1.7-7.2, P=0.001). The number of resected lymph nodes and aortocaval lymph node sampling were not identified as predictors in multivariable analysis.In this nationwide analysis, the rate of ISGPS grade B/C CL after pancreatoduodenectomy was 7.0%. Although CL is associated with a prolonged hospital stay, the clinical impact is relatively minor in the vast majority (98%) of patients. Vascular resection and open surgery are predictors of CL.

OBJECTIVE: This analysis aimed to compare failure to rescue (FTR) after pancreatoduodenectomy across the Atlantic. SUMMARY BACKGROUND DATA: FTR, or mortality after development of a major complication, is a quality metric originally created to compare hospital results. FTR has been studied in North American and Northern European patients undergoing pancreatoduodenectomy (PD). However, a direct comparison of FTR after PD between North America and Northern Europe has not been performed. METHODS: Patients who underwent PD in North America, the Netherlands, Sweden and Germany (GAPASURG dataset) were identified from their respective registries (2014-17). Patients who developed a major complication defined as Clavien-Dindo ≥3 or developed a grade B/C postoperative pancreatic fistula (POPF) were included. Preoperative, intraoperative, and postoperative variables were compared between patients with and without FTR. Variables significant on univariable analysis were entered into a logistic regression for FTR. RESULTS: Major complications occurred in 6188 of 22,983 patients (26.9%) after PD, and 504 (8.1%) patients had FTR. North American and Northern European patients with complications differed, and rates of FTR were lower in North America (5.4% vs 12%, P < 0.001). Fourteen factors from univariable analysis contributing to differences in patients who developed FTR were included in a logistic regression. On multivariable analysis, factors independently associated with FTR were age, American Society of Anesthesiology ≥3, Northern Europe, POPF, organ failure, life-threatening complication, nonradiologic intervention, and reoperation. CONCLUSIONS: Older patients with severe systemic diseases are more difficult to rescue. Failure to rescue is more common in Northern Europe than North America. In stable patients, management of complications by interventional radiology is preferred over reoperation.

Background We tested the added value of 3D-vision on procedure time and surgical performance during robotic pancreatoduodenectomy anastomoses in biotissue. Robotic surgery has the advantage of articulating instruments and 3D-vision. Consensus is lacking on the added value of 3D-vision during laparoscopic surgery. Given the improved dexterity with robotic surgery, the added value of 3D-vision may be even less with robotic surgery. Methods In this experimental randomized controlled cross-over trial, 20 surgeons and surgical residents from 5 countries performed robotic pancreaticojejunostomy and hepaticojejunostomy anastomoses in a biotissue organ model using the da Vinci® system and were randomized to start with either 3D- or 2D-vision. Primary endpoint was the time required to complete both anastomoses. Secondary endpoint was the objective structured assessment of technical skill (OSATS; range 12–60) rating; scored by two observers blinded to 3D/2D. Results Robotic 3D-vision reduced the combined operative time from 78.1 to 57.3 min (24.6% reduction, p p p = 0.003) compared to 2D (39.4 to 45.1 points, ± 5.5). Conclusion 3D-vision has a considerable added value during robotic pancreatoduodenectomy anastomoses in biotissue in both time reduction and improved surgical performance as compared to 2D-vision.

Background: Despite a lack of high-level evidence, current guidelines recommend laparoscopic left lateral sectionectomy (LLLS) as the routine approach over open LLS (OLLS). Randomized studies and propensity score matched studies on LLLS vs OLLS for all indications, including malignancy, are lacking.Methods: This international multicenter propensity score matched retrospective cohort study included consecutive patients undergoing LLLS or OLLS in six centers from three European countries (January 2000-December 2016). Propensity scores were calculated based on nine preoperative variables and LLLS and OLLS were matched in a 1:1 ratio. Short-term operative outcomes were compared using paired tests.Results: A total of 560 patients were included. Out of 200 LLLS, 139 could be matched to 139 OLLS. After matching, baseline characteristics were well balanced. LLLS was associated with shorter operative time (144 (110-200) vs 199 (138-283) minutes, P < 0.001), less blood loss (100 (50-300) vs 350 (100-750) mL, P = 0.005) and a 3-day shorter postoperative hospital stay (4 (3-7) vs 7 (5-9) days, P < 0.001).Conclusion: This international multicenter propensity score matched study confirms the superiority of LLLS over OLLS based on shorter postoperative hospital stay, operative time, and less blood loss thus validating current guideline advice.

Background Choledochoduodenostomy (CD) is believed to cause certain long-term complications, such as sump syndrome and reflux gastritis. Therefore, CD is considered inferior to a Roux-and-Y hepaticojejunostomy (HJ). The aim of this study was to compare short- and long-term outcomes following CD and HJ for benign biliary diseases. Methods This was a retrospective, matched case-control study of patients undergoing biliary-digestive anastomosis for benign diseases between 2000 and 2016 in a tertiary centre. Patients undergoing CD and HJ were matched 1:1 based on age, sex, ASA-classification, indication, history of abdominal surgery or acute cholecystitis/pancreatitis. Short- and long-term outcomes were compared. Results Of 336 patients undergoing biliary-digestive anastomoses, 27 patients underwent CD. Matching resulted in two comparable groups of 26 patients each. Overall morbidity after HJ and CD was comparable: 30.8% versus 26.9% (p>0.999). Long-term complications occurred in 23.1% after HJ, and in 50% after CD (p=0.118). After CD, 2 patients (7.7%) developed sump syndrome. Both patients with an anastomotic stricture after HJ could be managed by endoscopic/radiological re-intervention, whilst all six patients with a stricture after CD required surgical re-intervention (p=0.016). Conclusion Although short-term complications were comparable, the number of anastomotic strictures was higher in patients undergoing CD. We therefore conclude that HJ is the biliary bypass of choice while CD should be performed in selected patients only.

Contains fulltext : 251535.pdf (Publisher’s version ) (Open Access) BACKGROUND: Previous studies reported a higher rate of postoperative pancreatic fistula after minimally invasive distal pancreatectomy compared to open distal pancreatectomy. It is unknown whether the clinical impact of postoperative pancreatic fistula after minimally invasive distal pancreatectomy is comparable with that after open distal pancreatectomy. We aimed to compare not only the incidence of postoperative pancreatic fistula, but more importantly, also its clinical impact. METHODS: This is a post hoc analysis of a multicenter randomized trial investigating a possible beneficial impact of a fibrin patch on the rate of clinically relevant postoperative pancreatic fistula (International Study Group for Pancreatic Surgery grade B/C) after distal pancreatectomy. Primary outcomes of the current analysis are the incidence and clinical impact of postoperative pancreatic fistula after both minimally invasive distal pancreatectomy and open distal pancreatectomy. RESULTS: From October 2010 to August 2017, 252 patients undergoing distal pancreatectomy were randomized, and data of 247 patients were available for analysis: 87 minimally invasive distal pancreatectomy and 160 open distal pancreatectomies. The postoperative pancreatic fistula rate after minimally invasive distal pancreatectomy was significantly higher than that after open distal pancreatectomy (28.7% vs 16.9%, P = .029). More patients were discharged with an abdominal surgical drain after minimally invasive distal pancreatectomy compared to open distal pancreatectomy (30/87, 34.5% vs 26/160, 16.5%, P = .001). In patients with postoperative pancreatic fistula, additional percutaneous catheter drainage procedures were performed less often (52% vs 84.6%, P = .012), with fewer drainage procedures (median [range], 2 [1-4] vs 2, [1-7], P = .014) after minimally invasive distal pancreatectomy. CONCLUSION: In this post hoc analysis, the postoperative pancreatic fistula rate after minimally invasive distal pancreatectomy was higher than that after open distal pancreatectomy, whereas the clinical impact was less.

Background Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection. Methods We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low-medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671. Findings From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 [8%] of 863 patients vs 124 [14%] of 885 patients; adjusted risk ratio [RR] 0middot48, 95% CI 0middot38-0middot61; p

Background: Surgical outcome after pancreatoduodenectomy for duodenal adenocarcinoma could differ from pancreatoduodenectomy for other cancers, but large multicenter series are lacking. This study aimed to determine surgical outcome in patients after pancreatoduodenectomy for duodenal adenocarcinoma, compared with other periampullary cancers, in a nationwide multicenter cohort. Methods: After pancreatoduodenectomy for cancer between 2014 and 2019, consecutive patients were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. Patients were stratified by diagnosis. Baseline, treatment characteristics, and postoperative outcome were compared between groups. The association between diagnosis and major complications (Clavien–Dindo grade III or higher) was assessed via multivariable regression analysis. Results: Overall, 3113 patients, after pancreatoduodenectomy for cancer, were included in this study: 264 (8.5%) patients with duodenal adenocarcinomas and 2849 (91.5%) with other cancers. After pancreatoduodenectomy for duodenal adenocarcinoma, patients had higher rates of major complications (42.8% vs. 28.6%; p

BACKGROUND Preoperative biliary drainage in patients with presumed resectable perihilar cholangiocarcinoma (PHC) is hypothesized to promote the occurrence of seeding metastases. Seeding metastases can occur at the surgical scars or at the site of postoperative drains, and in case of percutaneous biliary drainage, at the catheter port-site. To prevent seeding metastases after resection, we routinely treated PHC patients with preoperative radiotherapy (RT) for over 25 years until January 2018. AIM To investigate the incidence of seeding metastases following resection of PHC. METHODS All patients who underwent resection for pathology proven PHC between January 2000 and March 2019 were included in this retrospective study. Between 2000-January 2018, patients received preoperative RT (3 × 3.5 Gray). RT was omitted in patients treated after January 2018. RESULTS A total of 171 patients underwent resection for PHC between January 2000 and March 2019. Of 171 patients undergoing resection, 111 patients (65%) were treated with preoperative RT. Intraoperative bile cytology showed no difference in the presence of viable tumor cells in bile of patients undergoing preoperative RT or not. Overall, two patients (1.2%) with seeding metastases were identified, both in the laparotomy scar and both after preoperative RT (one patient with endoscopic and the other with percutaneous and endoscopic biliary drainage). CONCLUSION The incidence of seeding metastases in patients with resected PHC in our series was low (1.2%). This low incidence and the inability of providing evidence that preoperative low-dose RT prevents seeding metastases, has led us to discontinue preoperative RT in patients with resectable PHC in our center.