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Aim: To investigate the impact of total pancreatectomy (TP) on oncological outcomes for patients at high-risk of local recurrence or secondary progression in the remnant gland after partial pancreatectomy (PP) for IPMN-associated cancer., Summary Background Data: Major risk factors for invasive progression in the remnant gland include multifocality, diffuse main duct dilation, and the presence of invasive cancer. In these high-risk patients, a TP may be oncologically beneficial. However, current guidelines discourage TP, especially in elderly patients., Methods: This international multicenter study compares TP versus PP in patients with adenocarcinoma arising from multifocal or diffuse IPMN (2002-2022). Log-rank test and multivariable Cox-analysis with interaction analysis was performed to assess overall survival (OS), disease-free survival (DFS), and local-DFS., Results: Of 359 included patients, 162 (45%) were treated with TP, whereas 197 (55%) underwent PP. Despite TP and PP having similar R0-rates (59% vs. 58%, P=0.866), patients undergoing a TP had significantly longer local-DFS compared to PP (P=0.039). However, no difference in OS was observed between the two surgical approaches (P=0.487). In a multivariable analysis, young age (optimal cut-off ≤63.6 yrs) was associated with an OS benefit derived from TP (HR:0.44, 95%CI:0.22-0.89), whereas no significant difference was observed in elderly patients (HR:1.24, 95%CI:0.92-1.67, Pinteraction=0.007)., Conclusion: Since overall, patients with diffuse or multifocal IPMN with an invasive component do not benefit from TP in terms of OS, the indication for TP may be individualized to young patients who have sufficient life expectancy to benefit from the prevention of secondary progression or local recurrence., Competing Interests: Conflicts of Interest: None declared. Disclosures: There are no conflicts of interest for any of the authors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To measure the rate of LTS in resected PDAC and determine the association between predictors of OS and LTS., Summary Background Data: Long-term survival (>5 y, LTS) remains rare in pancreatic ductal adenocarcinoma (PDAC). Multiple predictors of overall survival (OS) are known but their association with LTS remains unclear., Methods: An international, multicenter retrospective study was conducted. Included were patients from 2012-2019 with resected PDAC. Excluded were those with metastases at diagnosis or resection, R2 resections, and 90-day mortality. Predictors of OS were identified using multivariable Cox regression and their prevalence in patients with LTS assessed. LTS was calculated by excluding patients with shorter follow-up and predictors of LTS were identified using multivariable logistic regression., Results: 3,003 patients were included (27.4% received neoadjuvant chemotherapy). Elevated baseline CA19-9, high tumor grade, nodal disease, and perineural and lymphovascular invasion were negative independent predictors of OS, while receipt of adjuvant chemotherapy predicted improved OS (all P<0.05). LTS was observed in 220/2,436 patients (9.0%), of whom 198 (90%) harbored poor prognostic factors: elevated baseline CA19-9 (58.1%), poor tumor differentiation (51.0%), nodal disease (46.8%), and perineural invasion (76.0%). Of those without any of these four features, 50.0% achieved LTS as compared to 21.3%, 13.3%, 5.2%, and 3.5% in those with 1, 2, 3, or 4 features., Conclusions: This bi-national cohort demonstrates a true LTS rate of 9.0% in resected PDAC. Clinicians should remain aware that presence of poor prognostic factors does not preclude LTS., Competing Interests: Conflicts of Interest: The authors declare that there are no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The use of surgery in patients with locally advanced pancreatic cancer (LAPC) following induction chemotherapy is increasing. However, most series do not report on the total cohort of patients undergoing surgical exploration; therefore, this single-center study investigates outcomes among all consecutive patients with LAPC who underwent surgical exploration., Methods: We conducted a retrospective, single-center analysis including all consecutive patients with LAPC (Dutch Pancreatic Cancer Group criteria) who underwent surgical exploration with curative intent (January 2014-June 2023) after induction therapy. Primary outcomes were resection rate and overall survival (OS) from the time of diagnosis., Results: Overall, 127 patients underwent surgical exploration for LAPC, whereby 100 patients (78.7%) underwent resection and 27 patients (21.3%) underwent a non-therapeutic laparotomy due to the extent of vascular involvement (n = 11, 8.7%) or occult metastases (n = 16, 12.6%). The overall in-hospital/30-day mortality rate was 0.8% and major morbidity was 31.3% (in patients after resection: 1.0% and 33.3%, respectively). The overall 90-day mortality rate was 5.5%, which included 3.1% mortality due to disease progression. Resection was associated with longer median OS {29 months (95% confidence interval [CI] 26-43) vs. 17 months (95% CI 11-26); p < 0.001} compared with patients undergoing non-therapeutic laparotomy, with corresponding 5-year OS rates of 28.4% and 7.7%. In Cox proportional hazard regression analysis, only pancreatic body/tail tumors independently predicted OS (hazard ratio 1.788 [95% CI 1.042-3.068])., Conclusion: This single-center series found a resection rate of 78.7% in patients with LAPC selected for surgical exploration, with a low risk of mortality and morbidity in all explored patients and a 5-year OS rate after resection of 28.4%., (© 2024. The Author(s).)

Background: Pancreatic adenocarcinoma located in the pancreatic body might require a portomesenteric venous resection (PVR), but data regarding surgical risks after distal pancreatectomy (DP) with PVR are sparse. Insight into additional surgical risks of DP-PVR could support preoperative counseling and intraoperative decision making. This study aimed to provide insight into the surgical outcome of DP-PVR, including its potential risk elevation over standard DP., Methods: We conducted a retrospective, multicenter study including all patients with pancreatic adenocarcinoma who underwent DP ± PVR (2018-2020), registered in four audits for pancreatic surgery from North America, Germany, Sweden, and The Netherlands. Patients who underwent concomitant arterial and/or multivisceral resection(s) were excluded. Predictors for in-hospital/30-day major morbidity and mortality were investigated by logistic regression, correcting for each audit., Results: Overall, 2924 patients after DP were included, of whom 241 patients (8.2%) underwent DP-PVR. Rates of major morbidity (24% vs. 18%; p = 0.024) and post-pancreatectomy hemorrhage grade B/C (10% vs. 3%; p = 0.041) were higher after DP-PVR compared with standard DP. Mortality after DP-PVR and standard DP did not differ significantly (2% vs. 1%; p = 0.542). Predictors for major morbidity were PVR (odds ratio [OR] 1.500, 95% confidence interval [CI] 1.086-2.071) and conversion from minimally invasive to open surgery (OR 1.420, 95% CI 1.032-1.970). Predictors for mortality were higher age (OR 1.087, 95% CI 1.045-1.132), chronic obstructive pulmonary disease (OR 4.167, 95% CI 1.852-9.374), and conversion from minimally invasive to open surgery (OR 2.919, 95% CI 1.197-7.118), whereas concomitant PVR was not associated with mortality., Conclusions: PVR during DP for pancreatic adenocarcinoma in the pancreatic body is associated with increased morbidity, but can be performed safely in terms of mortality., (© 2024. The Author(s).)

Objective: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others., Summary Background Data: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking., Methods: International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored six standardized case vignettes. This variability and the 'within centers' variability were calculated for twofold scoring (no complication/grade A vs grade B/C) and threefold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula (POPF), post-pancreatoduodenectomy hemorrhage (PPH), chyle leak (CL), bile leak (BL), and delayed gastric emptying (DGE). Interobserver variability is presented with Gwet's AC-1 measure for agreement., Results: Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for twofold scoring was 68% (95%-CI: 55%-81%, AC1 score: moderate agreement) and for threefold scoring 55% (49%-62%, AC1 score: fair agreement). The mean 'within centers' agreement for twofold scoring was 84% (80%-87%, AC1 score; substantial agreement)., Conclusion: The interobserver variability for the ISGPS defined complications of pancreatoduodenectomy was too high even though the 'within centers' agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability., Competing Interests: Conflicts of Interest and Source of Funding: No conflicts of interest declared or source of funding, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The appropriate surgical approach for pancreatic ductal adenocarcinoma (PDAC) is determined by the tumor's relation to the porto-mesenteric axis. Although the extent and location of lymphadenectomy is dependent on the type of resection, a pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) are considered equivalent oncologic operations for pancreatic neck tumors. Therefore, we aimed to assess differences in histopathological and oncological outcomes for surgical approaches in the treatment of pancreatic neck tumors., Methods: Patients with resected PDAC located in the pancreatic neck were identified from the National Cancer Database (2004-2020). Patients with metastatic disease were excluded. Furthermore, patients with 90-day mortality and R2-resections were excluded from the multivariable Cox-regression analysis., Results: Among 846 patients, 58% underwent PD, 25% DP, and 17% TP with similar R0-resection rates (p = 0.722). Significant differences were observed in nodal positivity (PD:44%, DP:34%, TP:57%, p < 0.001) and mean-number of examined lymph nodes (PD:17.2 ± 10.4, DP:14.7 ± 10.5, TP:21.2 ± 11.0, p < 0.001). Furthermore, inadequate lymphadenectomy (< 12 nodes) was observed in 30%, 44%, and 19% of patients undergoing PD, DP, and TP, respectively (p < 0.001). Multivariable analysis yielded similar overall survival after DP (HR:0.83, 95%CI:0.63-1.11), while TP was associated with worse survival (HR:1.43, 95%CI:1.08-1.89) compared to PD., Conclusion: While R0-rates are similar amongst all approaches, DP is associated with inadequate lymphadenectomy which may result in understaging disease. However, this had no negative influence on survival. In the premise that an oncological resection of the pancreatic neck tumor is feasible with a partial pancreatectomy, no benefit is observed by performing a TP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking., Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy., Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months., Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection., Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively., Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89)., Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Objective: This nationwide multicenter study aimed to define clinically relevant thresholds of relative serum CA19-9 response after 2 months of induction chemotherapy in patients with locally advanced pancreatic cancer (LAPC)., Background: CA19-9 is seen as leading biomarker for response evaluation in patients with LAPC, but early clinically useful cut-offs are lacking., Methods: All consecutive patients with LAPC after 4 cycles (m)FOLFIRINOX or 2 cycles gemcitabine-nab-paclitaxel induction chemotherapy (±radiotherapy) with CA19-9 ≥5 U/mL at baseline were analyzed (2015-2019). The association of CA19-9 response with median OS (mOS) was evaluated for different CA19-9 cut-off points. Minimum and optimal CA19-9 response were established via log-rank test. Predictors for OS were analyzed using COX regression analysis., Results: Overall, 212 patients were included, of whom 42 (19.8%) underwent resection. Minimum CA19-9 response demonstrating a clinically significant median OS difference (12.7 vs. 19.6 months) was seen at ≥40% CA19-9 decrease. The optimal cutoff for CA19-9 response was ≥60% decrease (21.7 vs. 14.0 mo, P =0.021). Only for patients with elevated CA19-9 levels at baseline (n=184), CA19-9 decrease ≥60% [hazard ratio (HR)=0.59, 95% CI, 0.36-0.98, P =0.042] was independently associated with prolonged OS, as were SBRT (HR=0.42, 95% CI, 0.25-0.70; P =0.001), and resection (HR=0.25, 95% CI, 0.14-0.46, P <0.001), and duration of chemotherapy (HR=0.75, 95% CI, 0.69-0.82, P <0.001)., Conclusions: CA19-9 decrease of ≥60% following induction chemotherapy as optimal response cut-off in patients with LAPC is an independent predictor for OS when CA19-9 is increased at baseline. Furthermore, ≥40% is the minimum cut-off demonstrating survival benefit. These cut-offs may be used when discussing treatment strategies during early response evaluation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it is unclear how this translates to nationwide clinical practice and outcome. This study aims to assess the nationwide use and outcome of resection of LAPC following induction chemo(radio)therapy., Patients and Methods: A multicenter retrospective study including all patients who underwent resection for LAPC following chemo(radio)therapy in all 16 Dutch pancreatic surgery centers (2014-2020), registered in the mandatory Dutch Pancreatic Cancer Audit. LAPC is defined as arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion., Results: Overall, 142 patients underwent resection for LAPC, of whom 34.5% met the 2022 National Comprehensive Cancer Network criteria. FOLFIRINOX was the most commonly (93.7%) used chemotherapy [median 5 cycles (IQR 4-8)]. Venous and arterial resections were performed in 51.4% and 14.8% of patients. Most resections (73.9%) were performed in high-volume centers (i.e., ≥ 60 pancreatoduodenectomies/year). Overall median volume of LAPC resections/center was 4 (IQR 1-7). In-hospital/30-day major morbidity was 37.3% and 90-day mortality was 4.2%. Median OS from diagnosis was 26 months (95% CI 23-28) and 5-year OS 18%. Surgery in high-volume centers [HR = 0.542 (95% CI 0.318-0.923)], ypN1-2 [HR = 3.141 (95% CI 1.886-5.234)], and major morbidity [HR = 2.031 (95% CI 1.272-3.244)] were associated with OS., Conclusions: Resection of LAPC following chemo(radio)therapy is infrequently performed in the Netherlands, albeit with acceptable morbidity, mortality, and OS. Given these findings, a structured nationwide approach involving international centers of excellence would be needed to improve selection of patients with LAPC for surgical resection following induction therapy., (© 2023. Society of Surgical Oncology.)

Background: Surgery in selected patients with locally advanced pancreatic cancer after induction chemotherapy may have drawbacks related to surgical risks and breaks or delays in oncological treatment, in particular when curative intent resection is not possible (that is non-therapeutic laparotomy). The aim of this study was to assess the incidence and oncological impact of a non-therapeutic laparotomy in patients with locally advanced pancreatic cancer treated with induction (m)FOLFIRINOX chemotherapy., Methods: This was a retrospective international multicentre study including patients diagnosed with pathology-proven locally advanced pancreatic cancer treated with at least one cycle of (m)FOLFIRINOX (2012-2019). Patients undergoing a non-therapeutic laparotomy (group A) were compared with those not undergoing surgery (group B) and those undergoing resection (group C)., Results: Overall, 663 patients with locally advanced pancreatic cancer were included (67 patients (10.1%) in group A, 425 patients (64.1%) in group B, and 171 patients (25.8%) in group C). A non-therapeutic laparotomy occurred in 28.2% of all explorations (67 of 238), with occult metastases in 30 patients (30 of 67, 44.8%) and a 90-day mortality rate of 3.0% (2 of 67). Administration of palliative therapy (65.9% versus 73.1%; P = 0.307) and median overall survival (20.4 [95% c.i. 15.9 to 27.3] versus 20.2 [95% c.i. 19.1 to 22.7] months; P = 0.752) did not differ between group A and group B respectively. The median overall survival in group C was 36.1 (95% c.i. 30.5 to 41.2) months. The 5-year overall survival rates were 11.4%, 8.7%, and 24.7% in group A, group B, and group C, respectively. Compared with group B, non-therapeutic laparotomy (group A) was not associated with reduced overall survival (HR = 0.88 [95% c.i. 0.61 to 1.27])., Conclusion: More than a quarter of surgically explored patients with locally advanced pancreatic cancer after induction (m)FOLFIRINOX did not undergo a resection. Such non-therapeutic laparotomy does not appear to substantially impact oncological outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Introduction: About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative., Methods: This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37 U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics., Results: Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5 ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not., Conclusions: Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9., (© 2024. Society of Surgical Oncology.)

Objectives/background: High-output stoma is one of the most common major morbidities in young children with an enterostomy that could lead to intestinal failure. Management of high-output enterostomy in children is mostly based on personal experience. This systematic review aims to clarify the evidence-based therapeutic approach of high-output enterostomy in children., Methods: A systematic review was performed using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published until March 20, 2023, following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The study population comprised children (i.e., age <18 years) with high-output enterostomy (i.e., jejuno-, ileo-, and/or colostomy), regardless of underlying aetiology. Interventions comprised any (non)pharmacological and/or surgical treatment. Interventions were compared with each other, placebos, and/or no interventions. Primary outcome was reduction of enterostomy output. Secondary outcomes were morbidity, mortality, quality of life, associated healthcare costs, and adverse events., Results: The literature search identified 4278 original articles of which 366 were screened on full text, revealing that none of the articles met the inclusion criteria., Conclusion: This first systematic review on management of high-output enterostomy in children revealed that any evidence on the primary and secondary outcomes is lacking. There is an urgent need for evidence on conservative treatment strategies including fluid restrictions, dietary advices, oral rehydration solution, chyme re-infusion, and pharmacological and surgical treatments of high-output enterostomy in children, aiming to reduce the risk for short- and long-term complications. Till more evidence is available, a systematic and multidisciplinary step-up approach is needed. Therefore, a therapeutic work-up is proposed that could guide the care., (© 2023 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda., (© 2023. Springer Nature Limited.)

Objective: To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D., Summary Background Data: Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking., Methods: Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed., Results: Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P<0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%)., Conclusion: This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Gastric venous congestion (GVC) after total pancreatectomy (TP) is rarely studied despite its high 5% to 28% incidence and possible association with mortality. This study aimed to provide insight about incidence, risk factors, management, and outcome of GVC after TP., Methods: This retrospective observational single-center study included all patients undergoing elective TP from 2008 to 2021. The exclusion criteria ruled out a history of gastric resection, concomitant (sub)total gastrectomy for oncologic indication(s) or celiac axis resection, and postoperative (sub)total gastrectomy for indication(s) other than GVC., Results: The study enrolled 268 patients. The in-hospital major morbidity (Clavien-Dindo grade ≥IIIa) rate was 28%, and the 90-day mortality rate was 3%. GVC was identified in 21% of patients, particularly occurring during index surgery (93%). Intraoperative GVC was managed with (sub)total gastrectomy for 55% of the patients. The major morbidity rate was higher for the patients with GVC (44% vs 24%; p = 0.003), whereas the 90-day mortality did not differ significantly (5% vs 3%; p = 0.406). The predictors for major morbidity were intraoperative GVC (odds ratio [OR], 2.207; 95% confidence interval [CI], 1.142-4.268) and high TP volume (> 20 TPs/year: OR, 0.360; 95% CI, 0.175-0.738). The predictors for GVC were portomesenteric venous resection (PVR) (OR, 2.103; 95% CI, 1.034-4.278) and left coronary vein ligation (OR, 11.858; 95% CI, 5.772-24.362)., Conclusions: After TP, GVC is rather common (in 1 of 5 patients). GVC during index surgery is predictive for major morbidity, although not translating into higher mortality. Left coronary vein ligation and PVR are predictive for GVC, requiring vigilance during and after surgery, although gastric resection is not always necessary. More evidence on prevention, identification, classification, and management of GVC is needed., (© 2023. The Author(s).)

Objective: Examine the potential benefit of total pancreatectomy (TP) as an alternative to pancreatoduodenectomy (PD) in patients at high risk for postoperative pancreatic fistula (POPF)., Summary Background Data: TP is mentioned as an alternative to PD in patients at high risk for POPF, but a systematic review is lacking., Methods: Systematic review and meta-analyses using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published up to October 2022, comparing elective single-stage TP for any indication versus PD in patients at high risk for POPF. The primary endpoint was short-term mortality. Secondary endpoints were major morbidity (i.e., Clavien-Dindo grade ≥IIIa) on the short-term and quality of life., Results: After screening 1212 unique records, five studies with 707 patients (334 TP and 373 high-risk PD) met the eligibility criteria, comprising one randomized controlled trial and four observational studies. The 90-day mortality after TP and PD did not differ (6.3% vs. 6.2%; RR=1.04 [95%CI 0.56-1.93]). Major morbidity rate was lower after TP compared to PD (26.7% vs. 38.3%; RR=0.65 [95%CI 0.48-0.89]), but no significance was seen in matched/randomized studies (29.0% vs. 36.9%; RR = 0.73 [95%CI 0.48-1.10]). Two studies investigated quality of life (EORTC QLQ-C30) at a median of 30-52 months, demonstrating comparable global health status after TP and PD (77% [±15] vs. 76% [±20]; P =0.857)., Conclusions: This systematic review and meta-analysis found no reduction in short-term mortality and major morbidity after TP as compared to PD in patients at high risk for POPF. However, if TP is used as a bail-out procedure, the comparable long-term quality of life is reassuring., Competing Interests: M.D.C. has been awarded an industry grant (Haemonetics, Inc) to conduct a multicentre study to evaluate the prognostic implications of TEG in pancreatic cancer. M.D.C. is co-principal investigator of a Boston Scientific-sponsored international multicentre study on the use of intraoperative pancreatoscopy of patients with IPMN.The remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Restaging of locally advanced pancreatic cancer (LAPC) after induction chemotherapy using contrast-enhanced computed tomography (CE-CT) imaging is imprecise in evaluating local tumor response. This study explored the value of 3 Tesla (3 T) contrast-enhanced (CE) and diffusion-weighted (DWI) magnetic resonance imaging (MRI) for local tumor restaging., Methods: This is a prospective pilot study including 20 consecutive patients with LAPC with RECIST non-progressive disease on CE-CT after induction chemotherapy. Restaging CE-CT, CE-MRI, and DWI-MRI were retrospectively evaluated by two abdominal radiologists in consensus, scoring tumor size and vascular involvement. A halo sign was defined as replacement of solid perivascular (arterial and venous) tumor tissue by a zone of fatty-like signal intensity., Results: Adequate MRI was obtained in 19 patients with LAPC after induction chemotherapy. Tumor diameter was non-significantly smaller on CE-MRI compared to CE-CT (26 mm vs. 30 mm; p = 0.073). An MRI-halo sign was seen on CE-MRI in 52.6% (n = 10/19), whereas a CT-halo sign was seen in 10.5% (n = 2/19) of patients (p = 0.016). An MRI-halo sign was not associated with resection rate (60.0% vs. 62.5%; p = 1.000). In the resection cohort, patients with an MRI-halo sign had a non-significant increased R0 resection rate as compared to patients without an MRI-halo sign (66.7% vs. 20.0%; p = 0.242). Positive and negative predictive values of the CE-MRI-halo sign for R0 resection were 66.7% and 66.7%, respectively., Conclusions: 3 T CE-MRI and the MRI-halo sign might be helpful to assess the effect of induction chemotherapy in patients with LAPC, but its diagnostic accuracy has to be evaluated in larger series., (© 2022. The Author(s).)

Background: Rescue pancreatectomy for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) is associated with high mortality. However, in-depth literature is scarce and hard to interpret. This study aimed to evaluate the indications, timing and perioperative outcomes of rescue pancreatectomy for severe POPF after PD., Methods: Retrospective single-centre study from all consecutive patients (2008-2020) with POPF-C after PD (ISGPS 2016 definition). Major morbidity and mortality during hospitalization or within 90 days after index surgery were evaluated. Time from index surgery to rescue pancreatectomy was dichotomized in early and late (≤ 11 versus > 11 days)., Results: From 1076 PDs performed, POPF-B/C occurred in 190 patients (17.7%) of whom 53 patients (4.9%) with POPF-C were included. Mortality after early rescue pancreatectomy did not differ significantly compared to late rescue pancreatectomy (13.6% versus 35.3%; p = 0.142). Timing of a rescue pancreatectomy did not change significantly during the study period: 11 (IQR, 8-14) (2008-2012) versus 14 (IQR, 7-33) (2013-2016) versus 8 days (IQR, 6-11) (2017-2020) (p = 0.140). Over time, the mortality in patients with POPF grade C decreased from 43.5% in 2008-2012 to 31.6% in 2013-2016 up to 0% in 2017-2020 (p = 0.014). However, mortality rates after rescue pancreatectomy did not differ significantly: 31.3% (2008-2012) versus 28.6% (2013-2016) versus 0% (2017-2020) (p = 0.104)., Conclusions: Rescue pancreatectomy for severe POPF is associated with high mortality, but an earlier timing might favourably influence the mortality. Hypothetically, this could be of value for pre-existent vulnerable patients. These findings must be carefully interpreted considering the sample sizes and differences among subgroups by patient selection., (© 2022. The Author(s).)

Background: Total pancreatectomy (TP) is mentioned as alternative to pancreatoduodenectomy (PD) with high-risk pancreatojejunostomy (PJ) to avoid severe pancreatic fistula-related complications, but its benefit is controversial and comparative studies are scarce., Methods: Cross-sectional single-center study among patients after PD with high-risk PJ versus patients after single-stage elective TP for any indication (2015-2017), using propensity scores to evaluate surgical outcomes and long-term quality of life (QoL) in three risk strata. EORTC QLQ-C30 and EQ-5D-5L were used for QoL assessment., Results: Overall, 77 patients after TP (68.8%) and 102 patients after high-risk PD (34.5%) were included. Major morbidity (29.9% vs. 41.2%; p = 0.119) and 90-day mortality (5.2% vs. 8.8%; p = 0.354) did not differ significantly between TP and high-risk PD. Interventions for intra-abdominal fluid collections (9.1% vs. 23.5%, p = 0.011) and postpancreatectomy haemorrhage (6.5% vs. 18.6%; p = 0.018) were more often required after high-risk PD, but these differences did not remain after stratification. QoL was comparable after TP and high-risk PD (75% vs. 83%; p = 0.720), even after stratification., Conclusions: TP seems not to be inferior to high-risk PD regarding surgical outcomes and QoL. TP could be considered as an alternative to a very high-risk PD, but reluctance persists since TP does not appear to reduce mortality., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers., Summary of Background Data: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients., Methods: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018., Results: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS., Conclusion: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The impact of high-volume care in total pancreatectomy (TP) is barely explored since annual numbers are mostly low. This study evaluated surgical outcomes after TP over time in a high-volume center., Methods: All adult patients (age ≥ 18 years) who underwent an elective single-stage TP at Karolinska University Hospital were retrospectively analysed (2008-2017). High volume was defined as > 20 TPs/year., Results: Overall, 145 patients after TP were included, including 86 (59.3%) extended resections. Major morbidity was 34.5% (50/145) and 90-day mortality 5.5% (8/145). The relative use of TP within all pancreatectomies increased from 5.4% (63/1175) in 2008-2015 to 17.3% (82/473) in 2016-2017 (p < 0.001). Over time, TP was more often performed to achieve radicality (n = 11, 17.5% to n = 31, 37.8%; p = 0.007). In multivariable logistic regression analysis, an annual TP-volume of > 20 was associated with reduced major morbidity (odds ratio [OR] = 0.225, 95% confidence interval [CI], 0.097-0.521; p < 0.001). In the high-volume years (2016-2017), major morbidity (n = 31, 49.2% to n = 19, 23.2%; p = 0.001) and relaparotomy rate (n = 13, 20.6% to n = 5, 6.1%; p = 0.009) improved. Improvements occurred mainly after extended TP, including lower major morbidity (n = 22, 57.9% to n = 12, 25.0%; p = 0.002) and in-hospital mortality (n = 3, 7.9% to n = 0, 0%; p = 0.082)., Conclusions: In a single, high-volume center study, an increase in surgical volume of TP was associated with improved perioperative outcomes, especially for extended resections.

Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including "minimal" or "extensive" with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the "Materials and methods" section.

Objective: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers., Summary Background Data: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection., Methods: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998)., Results: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%., Conclusion: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

Objective: The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients' and clinicians' safety and safeguard health care capacity., Summary Background Data: The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer., Methods: An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery using 21 statements (April, 2020). Consensus was defined as >80% agreement among respondents and moderate agreement as 60% to 80% agreement., Results: A total of 337 respondents from 267 centers and 37 countries spanning 5 continents completed the survey. Most respondents were surgeons (n = 302, 89.6%) and working in an academic center (n = 286, 84.9%). The majority of centers (n = 166, 62.2%) performed less pancreatic surgery because of the COVID-19 pandemic, reducing the weekly pancreatic resection rate from 3 [interquartile range (IQR) 2-5] to 1 (IQR 0-2) (P < 0.001). Most centers screened for COVID-19 before pancreatic surgery (n = 233, 87.3%). Consensus was reached on 13 statements and 5 statements achieved moderate agreement., Conclusions: This global survey elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion.

Background: Total pancreatectomy (TP) is rarely performed due to concerns for endocrine and exocrine insufficiency and decreased quality of life (QoL). Renewed interest is seen in recent years, but large cohort studies remain scarce. This study was designed to evaluate endocrine and exocrine insufficiency after TP and its impact on QoL., Methods: Adult patients (age ≥ 18 years) who underwent TP between 2008 and 2017 at Karolinska University Hospital with at least 6 months follow-up were included. Endocrine and exocrine insufficiency and QoL were assessed using validated questionnaires (EORTC QLQ-C30, QLQ-PAN26, PAID20, and DTSQs). Both pre- and postoperative questionnaires were available in a subgroup., Results: Of 145 TP, 60 patients were eligible of whom 53 (88.3%) with a median of 21 months (interquartile range [IQR] 13-54) follow-up were included. Symptomatic hypoglycemia occurred in 90.6% (48/53) of patients, and 25% (12/48) experienced ≥ 1 episodes of loss of consciousness. The PAID20 revealed emotional burnout in seven patients (13.2%), whereas a high satisfaction score of diabetes treatment (median 28, IQR 24-32) was measured according to the DTSQs. Overall, 27 patients (50.9%) reported to have steatorrhea during a median of 2 days (IQR 0-4) in the past week. Overall QoL was reduced compared with a general population (66.7% vs. 76.4%; Δ9.7%) but did not differ with preoperative outcomes (n = 39, 66.7%; IQR 41.7-83.3 vs. 66.7%, IQR 50.0-83.3; P = 0.553) according to the EORTC QLQ-C30., Conclusions: Although the impact of endocrine and exocrine insufficiency on QoL after TP seems acceptable, the management of both insufficiencies should be further improved.

Background: Surgeons have traditionally been reluctant to perform total pancreatectomy because of concerns for brittle diabetes and poor quality of life (QoL). Several recent studies have suggested that outcomes following total pancreatectomy have improved, but a systematic review is lacking., Methods: A systematic review was undertaken of studies reporting on outcomes after total pancreatectomy for all indications, except chronic pancreatitis. PubMed, EMBASE (Ovid), and Cochrane Library were searched (2005-2018). Endpoints included functional outcome and QoL., Results: A total of 21 studies, including 1536 patients, fulfilled the eligibility criteria. During a median follow-up of 20·8 (range 1·5-96·0) months, 18·6 per cent (45 of 242 patients) were readmitted for endocrine-related morbidity, with associated mortality in 1·6 per cent (6 of 365 patients). No diabetes-related mortality was reported in studies including only patients treated after 2005. Symptoms related to exocrine insufficiency were reported by 43·5 per cent (143 of 329 patients) during a median follow-up of 15·9 (1·5-96·0) months. Overall QoL, reported by 102 patients with a median follow-up of 28·6 (6·0-66·0) months, using the EORTC QLQ-C30 questionnaire, showed a moderately reduced summary score of 76 per cent, compared with a general population score of 86 per cent (P = 0·004)., Conclusion: Overall QoL after total pancreatectomy is affected adversely, in particular by the considerable impact of diarrhoea that requires better treatment. There is also room for improvement in the management of diabetes after total pancreatectomy, particularly with regards to prevention of diabetes-related morbidity., (© 2019 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Background: Nationwide audits facilitate quality and outcome assessment of pancreatoduodenectomy. Differences may exist between countries but studies comparing nationwide outcomes of pancreatoduodenectomy based on audits are lacking. This study aimed to compare the German and Dutch audits for external data validation., Methods: Anonymized data from patients undergoing pancreatoduodenectomy between 2014 and 2016 were extracted from the German Society for General and Visceral Surgery StuDoQ|Pancreas and Dutch Pancreatic Cancer Audit, and compared using descriptive statistics. Univariable and multivariable risk analyses were undertaken., Results: Overall, 4495 patients were included, 2489 in Germany and 2006 in the Netherlands. Adenocarcinoma was a more frequent indication for pancreatoduodenectomy in the Netherlands. German patients had worse ASA fitness grades, but Dutch patients had more pulmonary co-morbidity. Dutch patients underwent more minimally invasive surgery and venous resections, but fewer multivisceral resections. No difference was found in rates of grade B/C postoperative pancreatic fistula, grade C postpancreatectomy haemorrhage and in-hospital mortality. There was more centralization in the Netherlands (1·3 versus 13·3 per cent of pancreatoduodenectomies in very low-volume centres; P < 0·001). In multivariable analysis, both hospital stay (difference 2·49 (95 per cent c.i. 1·18 to 3·80) days) and risk of reoperation (odds ratio (OR) 1·55, 95 per cent c.i. 1·22 to 1·97) were higher in the German audit, whereas risk of postoperative pneumonia (OR 0·57, 0·37 to 0·88) and readmission (OR 0·38, 0·30 to 0·49) were lower. Several baseline and surgical characteristics, including hospital volume, but not country, predicted mortality., Conclusion: This comparison of the German and Dutch audits showed variation in case mix, surgical technique and centralization for pancreatoduodenectomy, but no difference in mortality and pancreas-specific complications., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.)