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
Background: Due to centralization of pancreatic surgery, patients with pancreatic cancer are treated in pancreatic cancer networks, composed of referring hospitals (Spokes) and an expert center ... Show moreBackground: Due to centralization of pancreatic surgery, patients with pancreatic cancer are treated in pancreatic cancer networks, composed of referring hospitals (Spokes) and an expert center (Hub). This study aimed to investigate I) how pancreatic cancer networks are organized and II) evaluated by involved clinicians.Methods: Two online surveys were sent out between January-May 2022. Part I was sent out to the surgical network directors of all hospitals of the Dutch Pancreatic Cancer Group (DPCG). Part II was sent out to all involved clinicians in the Hubs-and-Spokes networks. Results: There was a large variety between the 15 networks concerning number of affiliated Spokes (1-7), annual pancreatoduodenectomies (20-129), and use of a service level agreement (SLA) (40%). More Spoke clinicians considered the Spoke the best location for diagnostic workup (74% vs 36%, P < 0.001). Only 30% of Spoke clinicians attended the Hubs multidisciplinary team meeting frequently. More Hub clinicians thought that exchange of patient information should be improved (37% vs 51%, P = 0.005).Conclusion: A large variety in Dutch pancreatic cancer networks was observed concerning number of affiliated Spokes, use of SLAs, and logistic aspects of network care. Improvement of network care concern agreements on diagnostic workup, use of SLA, Spoke participation in the MDT, and patient information exchange. Show less
Vietsch, E.E.; Latifi, D.; Verheij, M.; Oost, E.W.A. van der; Wilde, R.F. de; Haen, R.; ... ; Eijck, C.H.J. van 2023
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both... Show morePancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies. Show less
Objective: To assess the learning curve of pancreaticojejunostomy during robotic pancreatoduodenectomy (RPD) and to predict the risk of postoperative pancreatic fistula (POPF) by using the... Show moreObjective: To assess the learning curve of pancreaticojejunostomy during robotic pancreatoduodenectomy (RPD) and to predict the risk of postoperative pancreatic fistula (POPF) by using the objective structured assessment of technical skills (OSATS), taking the fistula risk into account.Background: RPD is a challenging procedure that requires extensive training and confirmation of adequate surgical performance. Video grading, modified for RPD, of the pancreatic anastomosis could assess the learning curve of RPD and predict the risk of POPF.Methods: Post hoc assessment of patients prospectively included in 4 Dutch centers in a nationwide LAELAPS-3 training program for RPD. Video grading of the pancreaticojejunostomy was performed by 2 graders using OSATS (attainable score: 12-60). The main outcomes were the combined OSATS of the 2 graders and POPF (grade B/C). Cumulative sum analyzed a turning point in the learning curve for surgical skill. Logistic regression determined the cutoff for OSATS. Patients were categorized for POPF risk (ie, low, intermediate, and high) based on the updated alternative fistula risk scores.Results: Videos from 153 pancreatic anastomoses were included. Median OSATS score was 48 (interquartile range: 41-52) points and with a turning point at 33 procedures. POPF occurred in 39 patients (25.5%). An OSATS score below 49, present in 77 patients (50.3%), was associated with an increased risk of POPF (odds ratio: 4.01, P=0.004). The POPF rate was 43.6% with OSATS < 49 versus 15.8% with OSATS >= 49. The updated alternative fistula risk scores category "soft pancreatic texture" was the second strongest prognostic factor of POPF (odds ratio: 3.37, P=0.040). Median cumulative surgical experience was 17 years (interquartile range: 8-21).Conclusions: Video grading of the pancreatic anastomosis in RPD using OSATS identified a learning curve and a reduced risk of POPF in case of better surgical performance. Video grading may provide a valid method to surgical training, quality control, and improvement. 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 determine the nationwide implementation and surgical outcome of minor and major robotic liver surgery (RLS) and assess the first phase of implementation of RLS during the learning... Show moreObjective:To determine the nationwide implementation and surgical outcome of minor and major robotic liver surgery (RLS) and assess the first phase of implementation of RLS during the learning curve. Background:RLS may be a valuable alternative to laparoscopic liver surgery. Nationwide population-based studies with data on implementation and outcome of RLS are lacking. Methods:Multicenter retrospective cohort study including consecutive patients who underwent RLS for all indications in 9 Dutch centers (August 2014-March 2021). Data on all liver resections were obtained from the mandatory nationwide Dutch Hepato Biliary Audit (DHBA) including data from all 27 centers for liver surgery in the Netherlands. Outcomes were stratified for minor, technically major, and anatomically major RLS. Learning curve effect was assessed using cumulative sum analysis for blood loss. Results:Of 9437 liver resections, 400 were RLS (4.2%) procedures including 207 minor (52.2%), 141 technically major (35.3%), and 52 anatomically major (13%). The nationwide use of RLS increased from 0.2% in 2014 to 11.9% in 2020. The proportion of RLS among all minimally invasive liver resections increased from 2% to 28%. Median blood loss was 150 mL (interquartile range 50-350 mL] and the conversion rate 6.3% (n=25). The rate of Clavien-Dindo grade >= III complications was 7.0% (n=27), median length of hospital stay 4 days (interquartile range 2-5) and 30-day/in-hospital mortality 0.8% (n=3). The R0 resection rate was 83.2% (n=263). Cumulative sum analysis for blood loss found a learning curve of at least 33 major RLS procedures. Conclusions:The nationwide use of RLS in the Netherlands has increased rapidly with currently one-tenth of all liver resections and one-fourth of all minimally invasive liver resections being performed robotically. Although surgical outcomes of RLS in selected patient seem favorable, future prospective studies should determine its added value. 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
Background: Data on surgical outcomes of laparoscopic liver resection (LLR) versus open liver resection (OLR) of benign liver tumour (BLT) are scarce. This study aimed to provide a nationwide... Show moreBackground: Data on surgical outcomes of laparoscopic liver resection (LLR) versus open liver resection (OLR) of benign liver tumour (BLT) are scarce. This study aimed to provide a nationwide overview of postoperative outcomes after LLR and OLR of BLT. Methods: This was a nationwide retrospective study including all patients who underwent liver resection for hepatocellular adenoma, haemangioma and focal nodular hyperplasia in the Netherlands from 2014 to 2019. Propensity score matching (PSM) was applied to compare 30-day overall and major morbidity and 30-day mortality after OLR and LLR. Results: In total, 415 patients underwent BLT resection of whom 230 (55.4%) underwent LLR. PSM for OLR and LLR resulted in 250 matched patients. Median (IQR) length of stay was shorter after LLR than OLR (4 versus 6 days, 5.0-8.0, p < 0.001). Postoperative 30-day overall morbidity was lower after LLR than OLR (12.0% vs. 22.4%, p = 0.043). LLR was associated with reduced 30-day overall morbidity in multivariable analysis (aOR:0.46, CI:0.22-0.95, p = 0.043). Both 30-day major morbidity and 30-day mortality were not different. Conclusions: LLR for BLT is associated with shorter hospital stay and reduced overall morbidity and is preferred if technically feasible. Show less