BACKGROUND:Studies have shown that severe postoperative complications after resection of pancreatic and periampullary cancer might have a negative effect on long-term oncological outcomes. The PORSCH trial showed that an algorithm for early recognition and minimally invasive management of complications after pancreatic resection significantly improved short-term clinical outcomes. The algorithm's effect on long-term survival remains to be determined. METHODS:Long-term oncological outcomes were evaluated post hoc in all patients included in the nationwide, stepped-wedge cluster-randomised PORSCH trial (Jan 8, 2018, to Nov 9, 2019, Netherlands Trial Register, NL6671) who underwent pancreatic resection for pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, ampullary carcinoma, or duodenal carcinoma. Cox proportional hazard regression was used to compare overall survival between algorithm-based care and usual care. The crude analyses accounted for the stepped-wedge design by adjusting for calendar time, hospital volume, and hospital as a frailty term. Adjusted analyses were adjusted for baseline factors associated with long-term survival (age at diagnosis, sex, American Society of Anesthesiologists score, preoperative carbohydrate antigen 19-9, neoadjuvant therapy, vascular resection, postoperative tumour size, number of positive lymph nodes, perineural invasion, tumour differentiation, and resection margin status). Adjusted differences in restricted mean survival time (RMST) were estimated between algorithm-based care and usual care, using the same adjustment set as the Cox models. A predefined subgroup analysis was performed for patients with pancreatic ductal adenocarcinoma. FINDINGS:In total, 1090 patients were included: 644 (59%) patients with pancreatic ductal adenocarcinoma, 175 (16%) patients with distal cholangiocarcinoma, 188 (17%) patients with ampullary carcinoma, and 83 (8%) patients with duodenal carcinoma. As of Jan 1, 2024, median follow-up was 56 months (IQR 48-63) for the 549 patients who received usual care and 48 months (35-53) for the 541 patients who received algorithm-based care. Unadjusted median overall survival was 24 months (95% CI 22-28) in the usual care group and 26 months (24-30) in the algorithm-based care group. The adjusted difference in RMST for overall survival over 36 months was 2·1 months (95% CI 0·6-3·7, p=0·0080), favouring algorithm-based care. Algorithm-based care was associated with improved overall survival (crude hazard ratio [HR] 0·85 [95% CI 0·71-1·02], p=0·076; adjusted HR 0·76 [0·62-0·93], p=0·0089). Overall survival differences between algorithm-based care and usual care were most pronounced in patients with pancreatic ductal adenocarcinoma (crude HR 0·78 [95% CI 0·62-0·97], p=0·028; adjusted HR 0·71 [0·56-0·90], p=0·0052). For these patients, the adjusted RMST differences up to 36 months favoured algorithm-based care by 2·5 months (95% CI 0·8-4·2, p=0·0046). INTERPRETATION:The PORSCH algorithm for early recognition and minimally invasive management of postoperative complications after pancreatic surgery is associated with increased long-term overall survival after resection of pancreatic or periampullary cancer. FUNDING:Dutch Cancer Society and St Antonius Research Fund.

Objective: To determine the nationwide use and outcome of tailored surgical treatment for symptomatic chronic pancreatitis (CP) as advised by recent guidelines. Background: Randomized trials have shown that surgery is superior to endoscopy in patients with symptomatic CP, although endoscopy remains popular. Recent guidelines advice to "tailor surgery" is based on pancreatic morphology, meaning that the least extensive procedure should be selected based on pancreatic morphology. However, nationwide and multicenter studies on tailored surgery for symptomatic CP are lacking. Methods: Nationwide multicenter retrospective analysis of consecutive patients undergoing surgical treatment for symptomatic CP in all 7 Dutch university medical centers (2010-2020). Outcomes included volume trend, major complications, 90-day mortality, postoperative opioid use, and clinically relevant pain relief. Surgical treatment was tailored based on the size of the main pancreatic duct and pancreatic head (eg, surgical drainage for a dilated pancreatic duct and normal size pancreatic head). Results: Overall, 381 patients underwent surgery for CP: 127 surgical drainage procedures (33%; mostly extended lateral pancreaticojejunostomy), 129 duodenum-preserving pancreatic head resections (34%, mostly Frey), and 125 formal pancreatic resections (33%, mostly distal pancreatectomy). The annual surgical volume increased slightly (Pearson r=0.744). Mortality (90-d) occurred in 6 patients (2%) and was nonsignificantly lower after surgical drainage (0%, 3%, 2%; P=0.139). Major complications (12%, 24%, 26%; P=0.012), postoperative pancreatic fistula grade B/C (0%, 3%, 22%; P=0.038), surgical reintervention (4%, 16%, 12%; P=0.006), and endocrine insufficiency ( 14%, 21%, 43%; P<0.001) occurred less often after surgical drainage. After a median follow-up of 11 months (interquartile range: 3-23), good rates of clinically relevant pain relief ( 83%, 69%, 80%; P=0.082) were observed and 81% of opioid users had stopped using (83%, 78%, and 84%; P=0.496). Conclusions: The use of surgery for symptomatic CP increased over the study period. Drainage procedures were associated with the best safety profile and excellent functional outcome, highlighting the importance of tailoring surgery based on pancreatic morphology.

IMPORTANCE Patients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach. OBJECTIVE To compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS Between April 2011 and September 2018, 88 patients with painful chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach in 30 hospitals in the Netherlands collaborating in the Dutch Pancreatitis Study Group as part of the ESCAPE randomized clinical trial. For the present cohort study, long-term clinical data were collected after the initial 18-month follow-up. Follow-up was completed in June 2022, and data analysis was performed in June 2023. EXPOSURE Patients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach. MAIN OUTCOMES AND MEASURES The primary end point was pain, assessed by the Izbicki pain score; secondary end points included patient-reported complete pain relief and satisfaction. Predefined subgroups included patients who progressed from endoscopy to surgery and those with ductal clearance obtained by endoscopy. Analysis was performed according to the intention-to-treat principle. RESULTS In this cohort study, 86 of 88 overall patients could be evaluated, with a mean (SD) follow-up period of 98 (16) months. Of 88 initial patients, 21 patients (24%) were female, and mean (SD) patient age was 61(10) years. At the end of long-term follow-up, the mean (SD) Izbicki pain score was significant lower (33 [31] vs 51 [31]) in the early surgery group, as was the rate of patient-reported complete pain relief (14 of 31 patients [45%] vs 6 of 30 patients [20%]), compared to the endoscopy-first group. After the initial 18-month follow-up, 11 of 43 patients in the early surgery group (26%) underwent reinterventions vs 19 of 43 patients in the endoscopy-first group (44%). At the end of follow-up, more patients in the early surgery group were "very satisfied" with their treatment (22 of 31 patients [71%] vs 10 of 30 patients [33%]). Patients who progressed from endoscopy to surgery (22 of 43 patients [51%]) had significantly worse mean (SD) Izbicki pain scores (33 [31] vs 52 [24]) compared to the early surgery group and had a lower rate of complete pain relief (55% for early surgery vs 12% for endoscopy first). In the endoscopy-first group, patients with endoscopic ductal clearance had similar mean (SD) Izbicki pain scores as the remaining patients (49 [34] vs 53 [28]). CONCLUSIONS AND RELEVANCE In this cohort study evaluating long-term outcomes of the ESCAPE randomized clinical trial, after approximately 8 years of follow-up, early surgery was superior to an endoscopy-first approach in patients with painful chronic pancreatitis and a dilated main pancreatic duct in pain scores and patient satisfaction. Notably, patients who progressed from endoscopy to surgery had worse outcomes compared to patients undergoing early surgery, and obtaining endoscopic ductal clearance did not improve outcomes.

BACKGROUND:Pancreatic resections for pancreatic neuroendocrine tumors (pNET) may experience a higher complication rate than for pancreatic ductal adenocarcinoma (PDAC). This study aimed to determine the rate of the novel composite "Ideal Outcome" measure after resection for pNET, using PDAC as reference. METHODS:This observational cohort study included all consecutive patients after pancreatic resection for pNET and PDAC using the nationwide Dutch Pancreatic Cancer Audit (2014-2021). The primary outcome was Ideal Outcome; absence of postoperative mortality, postoperative pancreatic fistulas (POPF) grade B/C, other major complications, prolonged length of stay, reoperations and readmissions. RESULTS:In total, 524 pNET and 2851 PDAC resections were included. The rate of Ideal Outcome was lower after resection for pNET (47.7% versus 55.7%; P<0.001) as compared to PDAC. This difference was driven by a lower rate of Ideal Outcome after pancreatoduodenectomy for pNET (37.7% versus 56.3%; P<0.001), with no difference after left pancreatectomy (54.5% versus 52.5%; P=0.598). Among the individual components of Ideal Outcome after pancreatoduodenectomy, the largest difference was a four times higher rate of POPF (32.1% versus 7.9%; P<0.001) after resection of pNET. CONCLUSION:Patients undergoing pancreatoduodenectomy for pNET have a reduced Ideal Outcome rate compared to patients with PDAC, related to a fourfold increased risk of POPF. This highlights the value of pNET-specific patient counseling and the need for effective POPF mitigation strategies.

BACKGROUND:Postoperative pancreatic fistula is the main driver of morbidity and mortality after pancreatoduodenectomy. In high-risk patients, the rate of postoperative pancreatic fistula approaches 50%, whereas it is below 5% in patients with pancreatic cancer who receive neoadjuvant chemoradiotherapy. The aim of this study was to evaluate the safety, feasibility, and efficacy of preoperative stereotactic body radiotherapy on the pancreatic neck transection margin in high-risk patients undergoing pancreatoduodenectomy to prevent postoperative pancreatic fistula. METHODS:In this prospective multicentre open-label single-arm trial (progressing from a safety run-in phase to a phase II design), patients undergoing pancreatoduodenectomy for neoplasms other than pancreatic ductal adenocarcinoma received a single preoperative stereotactic body radiotherapy dose of 12 Gy. Primary endpoints included safety (less than or equal to 15% grade 3-5 toxicity), feasibility (a significant change in pancreatic texture measured using a durometer), and efficacy (a 15% reduction in the grade B/C postoperative pancreatic fistula rate compared with patients from the Dutch Pancreatic Cancer Audit who were eligible but not included in this study). Secondary endpoints assessed tissue fibrosis (collagen density). RESULTS:Overall, 38 patients were included, of whom 33 (87%) completed the study protocol and were included in the per-protocol analysis. The safety cut-off was met, with 3% grade 3-5 toxicity. Pancreatic tissue treated with stereotactic body radiotherapy showed increased firmness using a durometer (median of 47 (interquartile range 36-57) versus 37 (interquartile range 30-41) Shore OO units; P < 0.001) and a higher collagen density (median of 6.1% (interquartile range 4.4%-9.5%) versus 4.6% (interquartile range 2.5%-7.4%); P = 0.003). The grade B/C postoperative pancreatic fistula rate with stereotactic body radiotherapy was 57.6% (95% c.i. 41% to 74%), compared with 34% (95% c.i. 27% to 42%) in audit controls (P = 0.011). CONCLUSION:Preoperative stereotactic body radiotherapy is safe in high-risk patients undergoing pancreatoduodenectomy and increases parenchymal firmness and fibrosis, but fails to show evidence of efficacy.

ImportancePatients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach.ObjectiveTo compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial.Design, Setting, and ParticipantsBetween April 2011 and September 2018, 88 patients with painful chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach in 30 hospitals in the Netherlands collaborating in the Dutch Pancreatitis Study Group as part of the ESCAPE randomized clinical trial. For the present cohort study, long-term clinical data were collected after the initial 18-month follow-up. Follow-up was completed in June 2022, and data analysis was performed in June 2023.ExposurePatients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach.Main Outcomes and MeasuresThe primary end point was pain, assessed by the Izbicki pain score; secondary end points included patient-reported complete pain relief and satisfaction. Predefined subgroups included patients who progressed from endoscopy to surgery and those with ductal clearance obtained by endoscopy. Analysis was performed according to the intention-to-treat principle.ResultsIn this cohort study, 86 of 88 overall patients could be evaluated, with a mean (SD) follow-up period of 98 (16) months. Of 88 initial patients, 21 patients (24%) were female, and mean (SD) patient age was 61 (10) years. At the end of long-term follow-up, the mean (SD) Izbicki pain score was significant lower (33 [31] vs 51 [31]) in the early surgery group, as was the rate of patient-reported complete pain relief (14 of 31 patients [45%] vs 6 of 30 patients [20%]), compared to the endoscopy-first group. After the initial 18-month follow-up, 11 of 43 patients in the early surgery group (26%) underwent reinterventions vs 19 of 43 patients in the endoscopy-first group (44%). At the end of follow-up, more patients in the early surgery group were “very satisfied” with their treatment (22 of 31 patients [71%] vs 10 of 30 patients [33%]). Patients who progressed from endoscopy to surgery (22 of 43 patients [51%]) had significantly worse mean (SD) Izbicki pain scores (33 [31] vs 52 [24]) compared to the early surgery group and had a lower rate of complete pain relief (55% for early surgery vs 12% for endoscopy first). In the endoscopy-first group, patients with endoscopic ductal clearance had similar mean (SD) Izbicki pain scores as the remaining patients (49 [34] vs 53 [28]).Conclusions and RelevanceIn this cohort study evaluating long-term outcomes of the ESCAPE randomized clinical trial, after approximately 8 years of follow-up, early surgery was superior to an endoscopy-first approach in patients with painful chronic pancreatitis and a dilated main pancreatic duct in pain scores and patient satisfaction. Notably, patients who progressed from endoscopy to surgery had worse outcomes compared to patients undergoing early surgery, and obtaining endoscopic ductal clearance did not improve outcomes.

Background: This study evaluates leading causes of in-hospital mortality after pancreatic resection nationwide to determine areas for improvement. Methods: This observational cohort study included all in-hospital mortality after pancreatic resection in the Netherlands (2014-2019). Each fatality was considered to be caused by local complications (i.e. directly related to surgery, located in surgical area) or systemic complications (e.g. cardiac or pulmonary). A blinded Expert Committee reviewed the postoperative course leading to death and identified potential quality improvement measures. Results: Out of 5345 patients undergoing pancreatic resection, 149 patients (2.8 %) died in-hospital. Local complications caused death in 126 patients (85 %) and systemic complications in 23 patients (15 %). Concerning local complications, the common leading causes of death were postoperative pancreatic fistula (n = 41) and thrombosis of vascular reconstructions (n = 23). Systemic cardiac (n = 8) and pulmonary (n = 7) complications caused death frequently. Potential areas for improvement were failure to rescue (n = 89; 60 %), prevention of complications (n = 34, 23 %) and patient selection (n = 14; 9 %). Conclusion: Local complications often caused death after pancreatic resection, mainly pancreatic fistula and vascular reconstruction failure. Failure to rescue was considered the most important area for improvement to decrease in-hospital mortality further.

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.

OBJECTIVE:To evaluate the performance of published fistula risk models by external validation, and to identify independent risk factors for postoperative pancreatic fistula (POPF).BACKGROUND:Multiple risk models have been developed to predict POPF after pancreatoduodenectomy. External validation in high-quality prospective cohorts is, however, lacking or only performed for individual models.METHODS:A post hoc analysis of data from the stepped-wedge cluster cluster-randomized Care After Pancreatic Resection According to an Algorithm for Early Detection and Minimally Invasive Management of Pancreatic Fistula versus Current Practice (PORSCH) trial was performed. Included were all patients undergoing pancreatoduodenectomy in the Netherlands (January 2018-November 2019). Risk models on POPF were identified by a systematic literature search. Model performance was evaluated by calculating the area under the receiver operating curves (AUC) and calibration plots. Multivariable logistic regression was performed to identify independent risk factors associated with clinically relevant POPF.RESULTS:Overall, 1358 patients undergoing pancreatoduodenectomy were included, of whom 341 patients (25%) developed clinically relevant POPF. Fourteen risk models for POPF were evaluated, with AUCs ranging from 0.62 to 0.70. The updated alternative fistula risk score had an AUC of 0.70 (95% confidence intervals [CI]: 0.69-0.72). The alternative fistula risk score demonstrated an AUC of 0.70 (95% CI: 0.689-0.71), whilst an AUC of 0.70 (95% CI: 0.699-0.71) was also found for the model by Petrova and colleagues. Soft pancreatic texture, pathology other than pancreatic ductal adenocarcinoma or chronic pancreatitis, small pancreatic duct diameter, higher body mass index, minimally invasive resection and male sex were identified as independent predictors of POPF.CONCLUSION:Published risk models predicting clinically relevant POPF after pancreatoduodenectomy have a moderate predictive accuracy. Their clinical applicability to identify high-risk patients and guide treatment strategies is therefore questionable.

Background: Postoperative cholangitis is a common complication after pancreatoduodenectomy that can occur with or without anatomical biliary obstruction. This study aimed to investigate the incidence, diagnosis, treatment, and risk factors of cholangitis after pancreatoduodenectomy. Methods: We performed a retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy in 2 Dutch tertiary pancreatic centers (2010-2019). Primary outcome was postoperative cholangitis, defined as systemic inflammation with abnormal liver tests without another focus of infection, at least 1 month after resection. Diagnostic and therapeutic strategies were evaluated. Two types of postoperative cholangitis were distinguished; obstructive cholangitis (benign stenosis of the hepaticojejunostomy) and nonobstructive cholangitis. Potential risk factors were identified using logistic regression analysis. Results: Postoperative cholangitis occurred in 93 of 900 patients (10.3%). Median time to first episode of cholangitis was 8 months (interquartile range 4-16) after pancreatoduodenectomy. Multiple episodes of cholangitis occurred in 44 patients (47.3%) and readmission was necessary in 83 patients (89.2%). No cholangitis-related mortality was observed. Obstructive cholangitis was seen in 37 patients (39.8%) and nonobstructive cholangitis in 56 patients (60.2%). Surgery was performed for cholangitis in 7 patients (7.5%) and consisted of revision of the hepaticojejunostomy or elongation of the biliary limb. Postoperative biliary leakage (odds ratio 2.56; 95% confidence interval 1.42-4.62; P 1 / 4 .0018) was independently associated with postoperative cholangitis. Conclusion: Postoperative cholangitis unrelated to cancer recurrence was seen in 10% of patients after pancreatoduodenectomy. Nonobstructive cholangitis was more common than obstructive cholangitis. Postoperative biliary leakage was an independent risk factor. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

INTRODUCTION:Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively.METHODS:Multicenter prospective nonrandomized pilot study included patients with moderate or severe pain (Numeric Rating Scale >= 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5 mg/kg was followed by continuous infusion at 1.5 mg/kg/hr. The dose was raised every 15 minutes until treatment response (up to a maximum 2 mg/kg/hr) and consecutively administered for 2 hours. Primary outcome was the mean difference in pain severity, preinfusion, and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease >= 1.3 points was considered clinically relevant.RESULTS:Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day 1 was 1.1 (SD +/- 1.3) points for patients with PDAC and 0.5 (SD +/- 1.7) for patients with CP. A clinically relevant decrease in BPI on day 1 was reported in 9 of 29 patients (31%), and this response lasted up to 1 month. No serious complications were reported, and only 3 minor complications (vertigo, nausea, and tingling of mouth). Treatment with lidocaine did not impact quality of life.DISCUSSION:Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.

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: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.

INTRODUCTION:Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). AIM:assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. PATIENTS AND METHODS:Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014-2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). RESULTS:691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89-100%), SFM-b6 was 44% (20-77%), and SFM-b5+6 was 65% (53-90%). All centers met the performance target RAS>85%. Only 9 out of 17 met the performance target SFM-b5+6 > 85%. CONCLUSION:This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated.

PURPOSE:Distal pancreatectomy (DP) is associated with a high complication rate of 30-50% with postoperative pancreatic fistula (POPF) as a dominant contributor. Adequate risk estimation for POPF enables surgeons to use a tailor-made approach. Assessment of the risk of POPF prior to DP can lead to the application of preventive strategies. The current study aims to validate the recently published preoperative and intraoperative distal fistula risk score (D-FRS) in a nationwide cohort.METHODS:This nationwide retrospective Dutch cohort study included all patients after DP for any indication, all of whom were registered in the Dutch Pancreatic Cancer Audit (DPCA) database between 2013 and 2021. The D-FRS was validated by filling in the probability equations with data from this cohort. The predictive capacity of the models was represented by an area under the receiver operating characteristic (AUROC) curve.RESULTS:A total of 896 patients underwent DP of which 152 (17%) developed POPF of whom 144 grade B (95%) and 8 grade C (5%). The preoperative D-FRS, consisting of the variables pancreatic neck thickness and pancreatic duct diameter, showed an AUROC of 0.73 (95%CI 0.68-0.78). The intraoperative D-FRS, comprising pancreatic neck, duct diameter, BMI, operating time, and soft pancreatic aspect, showed an AUROC of 0.69 (95%CI 0.64-0.74).CONCLUSION:The current study is the first nationwide validation of the preoperative and intraoperative D-FRS showing acceptable distinguishing capacity for only the preoperative D-FRS for POPF. Therefore, the preoperative score could improve prevention and mitigation strategies such as drain management, which is currently investigated in the multicenter PANDORINA trial.

Objective: To evaluate the performance of published fistula risk models by external validation, and to identify independent risk factors for postoperative pancreatic fistula (POPF). Background: Multiple risk models have been developed to predict POPF after pancreatoduodenectomy. External validation in high-quality prospective cohorts is, however, lacking or only performed for individual models. Methods: A post hoc analysis of data from the stepped-wedge cluster cluster-randomized Care After Pancreatic Resection According to an Algorithm for Early Detection and Minimally Invasive Management of Pancreatic Fistula versus Current Practice (PORSCH) trial was performed. Included were all patients undergoing pancreatoduodenectomy in the Netherlands (January 2018–November 2019). Risk models on POPF were identified by a systematic literature search. Model performance was evaluated by calculating the area under the receiver operating curves (AUC) and calibration plots. Multivariable logistic regression was performed to identify independent risk factors associated with clinically relevant POPF. Results: Overall, 1358 patients undergoing pancreatoduodenectomy were included, of whom 341 patients (25%) developed clinically relevant POPF. Fourteen risk models for POPF were evaluated, with AUCs ranging from 0.62 to 0.70. The updated alternative fistula risk score had an AUC of 0.70 (95% confidence intervals [CI]: 0.69–0.72). The alternative fistula risk score demonstrated an AUC of 0.70 (95% CI: 0.689–0.71), whilst an AUC of 0.70 (95% CI: 0.699–0.71) was also found for the model by Petrova and colleagues. Soft pancreatic texture, pathology other than pancreatic ductal adenocarcinoma or chronic pancreatitis, small pancreatic duct diameter, higher body mass index, minimally invasive resection and male sex were identified as independent predictors of POPF. Conclusion: Published risk models predicting clinically relevant POPF after pancreatoduodenectomy have a moderate predictive accuracy. Their clinical applicability to identify high-risk patients and guide treatment strategies is therefore questionable.

OBJECTIVE:To determine the nationwide use and outcome of tailored surgical treatment for symptomatic chronic pancreatitis (CP) as advised by recent guidelines. BACKGROUND:Randomized trials have shown that surgery is superior to endoscopy in patients with symptomatic CP, although endoscopy remains popular. Recent guidelines advice to "tailor surgery" is based on pancreatic morphology, meaning that the least extensive procedure should be selected based on pancreatic morphology. However, nationwide and multicenter studies on tailored surgery for symptomatic CP are lacking. METHODS:Nationwide multicenter retrospective analysis of consecutive patients undergoing surgical treatment for symptomatic CP in all 7 Dutch university medical centers (2010-2020). Outcomes included volume trend, major complications, 90-day mortality, postoperative opioid use, and clinically relevant pain relief. Surgical treatment was tailored based on the size of the main pancreatic duct and pancreatic head (eg, surgical drainage for a dilated pancreatic duct and normal size pancreatic head). RESULTS:Overall, 381 patients underwent surgery for CP: 127 surgical drainage procedures (33%; mostly extended lateral pancreaticojejunostomy), 129 duodenum-preserving pancreatic head resections (34%, mostly Frey), and 125 formal pancreatic resections (33%, mostly distal pancreatectomy). The annual surgical volume increased slightly (Pearson r =0.744). Mortality (90-d) occurred in 6 patients (2%) and was nonsignificantly lower after surgical drainage (0%, 3%, 2%; P =0.139). Major complications (12%, 24%, 26%; P =0.012), postoperative pancreatic fistula grade B/C (0%, 3%, 22%; P =0.038), surgical reintervention (4%, 16%, 12%; P =0.006), and endocrine insufficiency ( 14%, 21%, 43%; P <0.001) occurred less often after surgical drainage. After a median follow-up of 11 months (interquartile range: 3-23), good rates of clinically relevant pain relief ( 83%, 69%, 80%; P =0.082) were observed and 81% of opioid users had stopped using (83%, 78%, and 84%; P =0.496). CONCLUSIONS:The use of surgery for symptomatic CP increased over the study period. Drainage procedures were associated with the best safety profile and excellent functional outcome, highlighting the importance of tailoring surgery based on pancreatic morphology.