Objective: To assess the feasibility, proficiency, and mastery learning curves for robotic pancreatoduodenectomy (RPD) in "second-generation" RPD centers following a multicenter training program... Show moreObjective: To assess the feasibility, proficiency, and mastery learning curves for robotic pancreatoduodenectomy (RPD) in "second-generation" RPD centers following a multicenter training program adhering to the IDEAL framework.Background: The long learning curves for RPD reported from "pioneering" expert centers may discourage centers interested in starting an RPD program. However, the feasibility, proficiency, and mastery learning curves may be shorter in "second-generation" centers that participated in dedicated RPD training programs, although data are lacking. We report on the learning curves for RPD in "second-generation" centers trained in a dedicated nationwide program.Methods: Post hoc analysis of all consecutive patients undergoing RPD in 7 centers that participated in the LAELAPS-3 training program, each with a minimum annual volume of 50 pancreatoduodenectomies, using the mandatory Dutch Pancreatic Cancer Audit (March 2016-December 2021). Cumulative sum analysis determined cutoffs for the 3 learning curves: operative time for the feasibility (1) risk-adjusted major complication (Clavien-Dindo grade >= III) for the proficiency, (2) and textbook outcome for the mastery, (3) learning curve. Outcomes before and after the cutoffs were compared for the proficiency and mastery learning curves. A survey was used to assess changes in practice and the most valued "lessons learned."Results: Overall, 635 RPD were performed by 17 trained surgeons, with a conversion rate of 6.6% (n=42). The median annual volume of RPD per center was 22.56.8. From 2016 to 2021, the nationwide annual use of RPD increased from 0% to 23% whereas the use of laparoscopic pancreatoduodenectomy decreased from 15% to 0%. The rate of major complications was 36.9% (n=234), surgical site infection 6.3% (n=40), postoperative pancreatic fistula (grade B/C) 26.9% (n=171), and 30-day/in-hospital mortality 3.5% (n=22). Cutoffs for the feasibility, proficiency, and mastery learning curves were reached at 15, 62, and 84 RPD. Major morbidity and 30-day/in-hospital mortality did not differ significantly before and after the cutoffs for the proficiency and mastery learning curves. Previous experience in laparoscopic pancreatoduodenectomy shortened the feasibility (-12 RPDs, -44%), proficiency (-32 RPDs, -34%), and mastery phase learning curve (-34 RPDs, -23%), but did not improve clinical outcome.Conclusions: The feasibility, proficiency, and mastery learning curves for RPD at 15, 62, and 84 procedures in "second-generation" centers after a multicenter training program were considerably shorter than previously reported from "pioneering" expert centers. The learning curve cutoffs and prior laparoscopic experience did not impact major morbidity and mortality. These findings demonstrate the safety and value of a nationwide training program for RPD in centers with sufficient volume. Show less
BackgroundMalignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard... Show moreBackgroundMalignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs.MethodsThe ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs.DiscussionThe ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting. Show less
Background: Practice variation exists in venous resection during pancreatoduodenectomy, but little is known about the potential causes and consequences as large studies are lacking. This study... Show moreBackground: Practice variation exists in venous resection during pancreatoduodenectomy, but little is known about the potential causes and consequences as large studies are lacking. This study explores the potential causes and consequences of practice variation in venous resection during pan-creatoduodenectomy for pancreatic cancer in the Netherlands.Methods: This nationwide retrospective cohort study included patients undergoing pan-creatoduodenectomy for pancreatic cancer in 18 centers from 2013 through 2017.Results: Among 1,311 patients undergoing pancreatoduodenectomy, 351 (27%) had a venous resection, and the overall median annual center volume of venous resection was 4. No association was found between the center volume of pancreatoduodenectomy and the rate of venous resections, nor between patient and tumor characteristics and the rate of venous resections per center. Female sex, lower body mass index, neoadjuvant therapy, venous involvement, and stenosis on imaging were predictive for venous resection. Adjusted for these factors, 3 centers performed significantly more, and 3 centers performed significantly fewer venous resections than expected. In patients with venous resection, significantly less major morbidity (22% vs 38%) and longer overall survival (median 16 vs 12 months) were observed in centers with an above-median annual volume of venous resections (>4).Conclusion: Patient and tumor characteristics did not explain significant practice variation between centers in the Netherlands in venous resection during pancreatoduodenectomy for pancreatic cancer. The clinical outcomes of venous resection might be related to the volume of the procedure. Show less
BackgroundSurgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic... Show moreBackgroundSurgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach.MethodsThis multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and & LE; 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), irinotecan 150 mg/m(2) at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m(2)). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized.DiscussionThe multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. Show less
Objective:The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal (GI) tract in a large unselected cohort... Show moreObjective:The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal (GI) tract in a large unselected cohort of patients with necrotizing pancreatitis. Background:Perforation and fistula of the GI tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes, and treatment are lacking. Methods:We performed a post hoc analysis of a nationwide prospective database of 896 patients with necrotizing pancreatitis. GI tract perforation and fistula were defined as spontaneous or iatrogenic discontinuation of the GI wall. Multivariable logistic regression was used to explore risk factors and to adjust for confounders to explore associations of the GI tract perforation and fistula on the clinical course. Results:A perforation or fistula of the GI tract was identified in 139 (16%) patients, located in the stomach in 23 (14%), duodenum in 56 (35%), jejunum or ileum in 18 (11%), and colon in 64 (40%). Risk factors were high C-reactive protein within 48 hours after admission [odds ratio (OR): 1.19; 95% confidence interval (CI): 1.01-1.39] and early organ failure (OR: 2.76; 95% CI: 1.78-4.29). Prior invasive intervention was a risk factor for developing a perforation or fistula of the lower GI tract (OR: 2.60; 95% CI: 1.04-6.60). While perforation or fistula of the upper GI tract appeared to be protective for persistent intensive care unit-admission (OR: 0.11, 95% CI: 0.02-0.44) and persistent organ failure (OR: 0.15; 95% CI: 0.02-0.58), perforation or fistula of the lower GI tract was associated with a higher rate of new onset organ failure (OR: 2.47; 95% CI: 1.23-4.84). When the stomach or duodenum was affected, treatment was mostly conservative (n=54, 68%). Treatment was mostly surgical when the colon was affected (n=38, 59%). Conclusions:Perforation and fistula of the GI tract occurred in one out of six patients with necrotizing pancreatitis. Risk factors were high C-reactive protein within 48 hours and early organ failure. Prior intervention was identified as a risk factor for perforation or fistula of the lower GI tract. The clinical course was mostly affected by involvement of the lower GI tract. Show less
Objective:To develop a fistula risk score for auditing, to be able to compare postoperative pancreatic fistula (POPF) after pancreatoduodenectomy among hospitals. Background:For proper comparisons... Show moreObjective:To develop a fistula risk score for auditing, to be able to compare postoperative pancreatic fistula (POPF) after pancreatoduodenectomy among hospitals. Background:For proper comparisons of outcomes in surgical audits, case-mix variation should be accounted for. Methods:This study included consecutive patients after pancreatoduodenectomy from the mandatory nationwide Dutch Pancreatic Cancer Audit. Derivation of the score was performed with the data from 2014 to 2018 and validation with 2019 to 2020 data. The primary endpoint of the study was POPF (grade B or C). Multivariable logistic regression analysis was performed for case-mix adjustment of known risk factors. Results:In the derivation cohort, 3271 patients were included, of whom 479 (14.6%) developed POPF. Male sex [odds ratio (OR)=1.34; 95% confidence interval (CI): 1.09-1.66], higher body mass index (OR=1.07; 95% CI: 1.05-1.10), a final diagnosis other than pancreatic ductal adenocarcinoma/pancreatitis (OR=2.41; 95% CI: 1.90-3.06), and a smaller duct diameter (OR=1.43/mm decrease; 95% CI: 1.32-1.55) were independently associated with POPF. Diabetes mellitus (OR=0.73; 95% CI: 0.55-0.98) was independently associated with a decreased risk of POPF. Model discrimination was good with a C-statistic of 0.73 in the derivation cohort and 0.75 in the validation cohort (n=913). Hospitals differed in particular in the proportion of pancreatic ductal adenocarcinoma/pancreatitis patients, ranging from 36.0% to 58.1%. The observed POPF risk per center ranged from 2.9% to 25.4%. The expected POPF rate based on the 5 risk factors ranged from 11.6% to 18.0% among hospitals. Conclusions:The auditing fistula risk score was successful in case-mix adjustment and enables fair comparisons of POPF rates among hospitals. Show less
Objective:To describe outcome after pancreatic surgery in the first 6 years of a mandatory nationwide audit. Background:Within the Dutch Pancreatic Cancer Group, efforts have been made to improve... Show moreObjective:To describe outcome after pancreatic surgery in the first 6 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 (PD) and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between 3 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 (FTR) and in-hospital mortality. Results:Overall, 5345 patients were included, of whom 4227 after PD and 1118 after distal pancreatectomy. After PD, FTR improved from 13% to 7.4% [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.80, P<0.001] and in-hospital mortality decreased from 4.1% to 2.4% (OR 0.68, 95% CI 0.54-0.86, P=0.001), despite operating on more patients with age >75 years (18%-22%, P=0.006), American Society of Anesthesiologists score & GE;3 (19%-31%, P<0.001) and Charlson comorbidity score & GE;2 (24%-34%, P<0.001). The rates of textbook outcome (57%-55%, P=0.283) and major complications remained stable (31%-33%, P=0.207), whereas complication-related intensive care admission decreased (13%-9%, P=0.002). After distal pancreatectomy, improvements in FTR from 8.8% to 5.9% (OR 0.65, 95% CI 0.30-1.37, P=0.253) and in-hospital mortality from 1.6% to 1.3% (OR 0.88, 95% CI 0.45-1.72, P=0.711) were not statistically significant. Conclusions:During the first 6 years of a nationwide audit, in-hospital mortality and FTR after PD improved despite operating on more high-risk patients. Several collaborative efforts may have contributed to these improvements. Show less
In two RCTs, comparing neoadjuvant chemoradiotherapy (CRT) with upfront surgery in patients with resectable and borderline resectable pancreatic cancers, CRT was associated with better survival.... Show moreIn two RCTs, comparing neoadjuvant chemoradiotherapy (CRT) with upfront surgery in patients with resectable and borderline resectable pancreatic cancers, CRT was associated with better survival. There was no difference in treatment effect between patients with a baseline CA19-9 level higher or lower than 500 units/ml, meaning that neoadjuvant CRT should not be withheld because of a low CA19-9 concentration.Background Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. Methods In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. Results Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). Conclusion Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice. Show less
Objective:The aim of this study was to assess the clinical impact and risk factors of chyle leak (CL). Background:In 2017, the International Study Group for Pancreatic Surgery (ISGPS) published the... Show moreObjective:The aim of this study was to assess the clinical impact and risk factors of chyle leak (CL). Background: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. Methods: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. Results: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, P<0.001] 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, P<0.001) 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. Conclusions: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. Show less
INTRODUCTION: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is... Show moreINTRODUCTION: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is a lack of detailed data on the full clinical spectrum of DPD, which is critical for the development of better diagnostic and treatment strategies. METHODS: We performed a long-term post hoc analysis of a prospectively collected nationwide cohort of 896 patients with necrotizing pancreatitis (2005-2015). The median follow-up after hospital admission was 75 months (P25-P75: 41-151). Clinical outcomes of patients with and without DPD were compared using regression analyses, adjusted for potential confounders. Predictive features for DPD were explored. RESULTS: DPD was confirmed in 243 (27%) of the 896 patients and resulted in worse clinical outcomes during both the patient's initial admission and follow-up. During hospital admission, DPD was associated with an increased rate of new-onset intensive care unit admission (adjusted odds ratio [aOR] 2.52; 95% confidence interval [CI] 1.62-3.93), new-onset organ failure (aOR 2.26; 95% CI 1.45-3.55), infected necrosis (aOR 4.63; 95% CI 2.87-7.64), and pancreatic interventions (aOR 7.55; 95% CI 4.23-13.96). During long-term follow-up, DPD increased the risk of pancreatic intervention (aOR 9.71; 95% CI 5.37-18.30), recurrent pancreatitis (aOR 2.08; 95% CI 1.32-3.29), chronic pancreatitis (aOR 2.73; 95% CI 1.47-5.15), and endocrine pancreatic insufficiency (aOR 1.63; 95% CI 1.05-2.53). Central or subtotal pancreatic necrosis on computed tomography (OR 9.49; 95% CI 6.31-14.29) and a high level of serum C-reactive protein in the first 48 hours after admission (per 10-point increase, OR 1.02; 95% CI 1.00-1.03) were identified as independent predictors for developing DPD. DISCUSSION: At least 1 of every 4 patients with necrotizing pancreatitis experience DPD, which is associated with detrimental, short-term and long-term interventions, and complications. Central and subtotal pancreatic necrosis and high levels of serum C-reactive protein in the first 48 hours are independent predictors for DPD. Show less
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... Show moreBackground: 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.(c) 2023 Elsevier Inc. All rights reserved. Show less
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... Show moreBackground 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.This nationwide observational cohort study included 1052 patients and showed that major complications, including organ failure, have a negative impact on disease-free interval and overall survival after resection of pancreatic cancer. This effect was largely mediated by the use of adjuvant chemotherapy. Show less
Vissers, F.L.; Balduzzi, A.; Bodegraven, E.A. van; Hilst, J. van; Festen, S.; Abu Hilal, M.; ... ; Dutch Pancreatic Canc Grp 2023
Background. Surgical outcome after pancreatoduodenectomy for duodenal adenocarcinoma could differ from pancreatoduodenectomy for other cancers, but large multicenter series are lacking. This study... Show moreBackground. 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 < 0.001), postoperative pancreatic fistula (International Study Group of Pancreatic Surgery [ISGPS] grade B/C; 23.1% vs. 13.4%; p < 0.001), complication-related intensive care admission (14.3% vs. 10.3%; p = 0.046), re-interventions (39.8% vs. 26.6%; p < 0.001), in-hospital mortality (5.7% vs. 3.1%; p = 0.025), and longer hospital stay (15 days vs. 11 days; p < 0.001) compared with pancreatoduodenectomy for other cancers. In multivariable analysis, duodenal adenocarcinoma was independently associated with major complications (odds ratio 1.14, 95% confidence interval 1.03-1.27; p = 0.011). Conclusion. Pancreatoduodenectomy for duodenal adenocarcinoma is associated with higher rates of major complications, pancreatic fistula, re-interventions, and in-hospital mortality compared with patients undergoing pancreatoduodenectomy for other cancers. These findings should be considered in patient counseling and postoperative management. Show less
Objective:To assess feasibility and safety of a multicenter training program in robotic pancreatoduodenectomy (RPD) adhering to the IDEAL framework for implementation of surgical innovation.... Show moreObjective:To assess feasibility and safety of a multicenter training program in robotic pancreatoduodenectomy (RPD) adhering to the IDEAL framework for implementation of surgical innovation. Background: Good results for RPD have been reported from single center studies. However, data on feasibility and safety of implementation through a multicenter training program in RPD are lacking. Methods: A multicenter training program in RPD was designed together with the University of Pittsburgh Medical Center, including an online video bank, robot simulation exercises, biotissue drills, and on-site proctoring. Benchmark patients were based on the criteria of Clavien. Outcomes were collected prospectively (March 2016-October 2019). Cumulative sum analysis of operative time was performed to distinguish the first and second phase of the learning curve. Outcomes were compared between both phases of the learning curve. Trends in nationwide use of robotic and laparoscopic PD were assessed in the Dutch Pancreatic Cancer Audit. Results:Overall, 275 RPD procedures were performed in seven centers by 15 trained surgeons. The recent benchmark criteria for low-risk PD were met by 125 (45.5%) patients. The conversion rate was 6.5% (n = 18) and median blood loss 250ml [interquartile range (IQR) 150-500]. The rate of Clavien-Dindo grade >= III complications was 44.4% (n = 122), postoperative pancreatic fistula (grade B/C) rate 23.6% (n = 65), 90-day complication-related mortality 2.5% (n = 7) and 90-day cancer-related mortality 2.2.% (n = 6). Median postoperative hospital stay was 12 days (IQR 8-20). In the subgroup of patients with pancreatic cancer (n = 80), the major complication rate was 31.3% and POPF rate was 10%. Cumulative sum analysis for operative time found a learning curve inflection point at 22 RPDs (IQR 10-35) with similar rates of Clavien-Dindo grade >= III complications in the first and second phase (43.4% vs 43.8%, P = 0.956, respectively). During the study period the nationwide use of laparoscopic PD reduced from 15% to 1%, whereas the use of RPD increased from 0% to 25%. Conclusions:This multicenter RPD training program in centers with sufficient surgical volume was found to be feasible without a negative impact of the learning curve on clinical outcomes. Show less
Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of... Show moreHepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs < 50 mm compared to HCAs >= 50 mm. Changes in final postoperative diagnosis were assessed. We performed a retrospective study that included patients who underwent resection for (suspected) HCAs in the Netherlands from 2014 to 2019. Indication for resection was analyzed and stratified for small (<50 mm) and large (>= 50 mm) tumors. Logistic regression analysis was performed on factors influencing change in tumor diagnosis. Out of 222 patients who underwent surgery, 44 (20%) patients had a tumor <50 mm. Median age was 46 (interquartile range [IQR], 33-56) years in patients with small tumors and 37 (IQR, 31-46) years in patients with large tumors (p = 0.016). Patients with small tumors were more frequently men (21% vs. 5%, p = 0.002). Main indications for resection in patients with small tumors were suspicion of (pre)malignancy (55%), (previous) bleeding (14%), and male sex (11%). Patients with large tumors received operations because of tumor size >50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size <50 mm (adjusted odds ratio [aOR], 3.4; p < 0.01), male sex (aOR, 3.7; p = 0.03), and lack of hepatobiliary contrast-enhanced magnetic resonance imaging (CE-MRI) (aOR, 1.8; p = 0.04). Resection for small (suspected) HCAs was mainly indicated by suspicion of (pre)malignancy, whereas for large (suspected) HCAs, tumor size was the most prevalent indication. Male sex, tumor size <50 mm, and lack of hepatobiliary CE-MRI were independent risk factors for postoperative change in tumor diagnosis. Show less
Gils, L. van; Verbeek, R.; Wellerdieck, N.; Bollen, T.; Leeuwen, M. van; Schwartz, M.; ... ; Reg Acad Canc Ctr Utrecht RAKU 2022
Background: Guidelines recommend against preoperative biliary drainage (PBD) in patients with pancreatic head cancer if bilirubin levels are <250 mmol/l. However, patients with higher bilirubin... Show moreBackground: Guidelines recommend against preoperative biliary drainage (PBD) in patients with pancreatic head cancer if bilirubin levels are <250 mmol/l. However, patients with higher bilirubin levels undergo PBD, despite the lack of supporting evidence. This study aims to evaluate outcomes in patients with a bilirubin level >= 250 and < 250.Methods: Patients were identified from databases of 3 centers. Outcomes were compared in patients with a bilirubin level >= 250 versus <250 both at the time of diagnosis and directly prior to surgery.Results: 244 patients were included. PBD was performed in 64% (123/191) with bilirubin <250 at diagnosis and 91% (48/53) with bilirubin >= 250. PBD technical success (83% vs. 81%, p = 0.80) and PBD related complications (33% vs. 29%, p = 0.60) did not differ between these groups. Analyzing bilirubin levels >= 250 versus <250 directly prior to surgery, no differences in severe post-operative complications and mortality were found.Conclusions: In patients with a pancreatic head cancer, PBD technical success and complications, and severe postoperative complications did not differ between patients with a bilirubin level >= 250 and < 250. Our study does not support a different approach regarding PBD in patients with severe jaundice. Show less
Stoop, T.F.; Mackay, T.M.; Brada, L.J.H.; Harst, E. van der; Daams, F.; Land, F.R. van 't; ... ; Dutch Pancreatic Canc Grp 2022
Introduction: Arterial resections in pancreatic surgery may be planned to obtain a radical oncological resection, or unplanned after iatrogenic injury during dissection. Most data on planned... Show moreIntroduction: Arterial resections in pancreatic surgery may be planned to obtain a radical oncological resection, or unplanned after iatrogenic injury during dissection. Most data on planned arterial resection come from single, very-high-volume centres and suggest that these resections might be feasible and even beneficial after preoperative chemotherapy in highly selected patients with pancreatic cancer1–3. However, real-world data on such planned and unplanned arterial resection at a nationwide level are scarce4. Furthermore, distinctions between planned and unplanned arterial resection are seldomly reported, even though this might have clinical implications. The present study evaluated the incidence and surgical outcome of all planned and unplanned arterial resections for pancreatic and periampullary cancer in The Netherlands. Show less
