BACKGROUND:NAD(P)H quinone dehydrogenase 1 (NQO1), a detoxification enzyme regulated by the Nrf2 cytoprotective pathway, is overexpressed in pancreatic ductal adenocarcinoma (PDAC). NQO1 levels are also influenced by the C609T single-nucleotide polymorphism (SNP). We hypothesized that elevated NQO1 would confer chemoresistance in PDAC and predict poor patient outcome. METHODS:NQO1 tumor levels and germline C609T SNP status were assessed in archival samples from the European Study Group for Pancreatic Cancer (ESPAC) trials. NQO1 expression (H-score) was treated as continuous for survival regression analyses and dichotomized for visual summaries. Nrf2 or downstream gene induction was assessed in Nrf2 reporter mice or in PDAC cells following exposure to gemcitabine (Gem), 5-fluorouracil (5-FU), or the capecitabine (Cap) metabolite 5-fluoro-5'-deoxyuridine (5'-DFUR). Colony formation following NQO1 depletion was assessed. RESULTS:NQO1 tumor levels correlated with germline C609T SNP status (P < .001). Contrary to our hypothesis, high NQO1 expression was associated with improved survival in ESPAC-4 patients randomized to GemCap (HR = 0.87 [95% CI = 0.751 to 0.999]; P = .049), and had no association to outcome in the Gem-only treated arm (HR = 0.98 [95% CI = 0.78 to 1.23]; P = .867). Including genotype data did not improve predictive model performance. Neither Gem nor 5-FU induced Nrf2 in vivo. At high concentrations, they suppressed Nrf2/NQO1 in PDAC cells, an effect not mitigated by co-treatment with 5'-DFUR. NQO1 depletion experiments revealed that NQO1 inhibits colony formation. The strongest inhibition was observed when NQO1-positive cells were co-treated with Gem and 5'-DFUR, supporting our clinical data from ESPAC. CONCLUSION:High tumor NQO1 predicts better outcome following GemCap therapy.

BACKGROUND:Suturing complex anastomoses requires repetitive training for mastery. Expert tutoring is a limited and costly ressource. This study assessed the added value of surgical video instructions in expert-tutored hepatopancreatobiliary (HPB) surgery courses. METHODS:Trainees and tutors used QR codes to access instructional videos of pancreatico- and hepaticojejunostomy (04/2024-09/2025: Davos course for HPB Surgery; Hands-On- Course of the North-German Surgical Association; ESSO Course Pancreatic Surgery). After watching videos and performing anastomoses on 3D-biotissue organ models, participants anonymously completed standardized questionnaires. RESULTS:Out of 51 participants (20 residents; 31 specialists), most reported that QR codes facilitated video access (n=48, 96%). The majority found the videos useful (n=31, 62%). Most preferred a combination of expert tutoring and surgical video instructions (n=49, 96%) and agreed that expert tutoring was more effective when supported by videos (n=44, 86%). Furthermore, 28 (55%) participants felt they could improve their surgical skills with the videos in self-directed training without expert guidance. Older and more experienced participants were more likely to agree that videos added value to expert tutoring. CONCLUSION:Surgical video instructions were well accepted and perceived as valuable additions to expert-tutored courses on HPB anastomoses. Further studies should assess translation into improved training outcomes.

Bouveret's syndrome represents a rare variant of gallstone ileus characterized by the migration of a gallstone through a bilioenteric fistula into the duodenum, resulting in pyloric obstruction. We present the case of a 79-year-old woman who presented to a regional hospital with symptoms of vomiting and constipation. Diagnostic imaging revealed duodenal obstruction with multiple concretions and pneumobilia. An attempted endoscopic retrieval of the obstructing gallstones was complicated by an iatrogenic distal esophageal perforation, necessitating transfer to our tertiary care center for further management. Subsequent imaging and endoscopic assessment confirmed the findings and the patient underwent emergency surgical intervention comprising discontinuous resection of the perforated esophageal segment and excision of the cholecystoduodenal fistula. After clinical stabilization, esophageal reconstruction was performed 3 months later via retrosternal colon interposition. The postoperative course was uneventful. This case highlights the necessity of early interdisciplinary management and decision-making in gallstone-induced bowel obstructions and esophageal perforation.

BackgroundColorectal cancer (CRC) is among the most prevalent malignancies worldwide and remains the second leading cause of cancer-related death. Curative treatment approaches rely on R0 resection with adequate regional lymphadenectomy. Current international guidelines recommend a lymph node yield (LNY) of at least 12 lymph nodes to ensure accurate pathological staging and to guide decisions regarding adjuvant therapy. However, it remains controversial whether this historically established threshold is sufficient to optimize oncological outcomes. The aim of this study was to evaluate the association between operative LNY and clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) in patients undergoing curative resection for CRC.MethodsThis retrospective study included 333 patients who underwent colorectal cancer resection at a high-volume center in Germany between 2016 and 2023. Only patients with Union for International Cancer Control (UICC) stage I–III disease who underwent curative-intent R0 resection were included. Patients were stratified into two groups according to LNY: <20 versus ≥20 retrieved lymph nodes.ResultsLNY of ≥20 was associated with distinct tumor- and treatment-related characteristics, including advanced local tumor stage, microsatellite instability (MSI), colon cancer, right hemicolectomy, and absence of neoadjuvant treatment. No significant differences were observed between the groups regarding nodal stage, number of positive lymph nodes, lymphatic invasion, surgical approach, urgency of surgery, intraoperative blood loss, major postoperative morbidity, anastomotic leakage, chyle leak, reoperation or length of hospital stay. Higher LNY was not independently associated with improved OS or DFS in the overall cohort. Subgroup analyses stratified by UICC stage showed no significant association between LNY ≥20 on OS or DFS in stage I, II, or III disease. In procedure-specific analyses, LNY ≥20 was associated with improved OS after anterior rectal resection.ConclusionsOverall, these findings suggest that higher LNY is not a general prognostic determinant of oncological outcomes, but may have procedure-specific prognostic relevance.

BACKGROUND:Length of hospital stay (LOS) is a commonly reported postoperative outcome measure in pancreatic surgery. However, LOS may be influenced by various factors, including healthcare systems, cultural traditions, and readmission rate. This systematic review and meta-analysis investigated LOS in pancreatic surgery. METHODS:A meta-analysis was conducted to identify all randomized clinical trials (RCTs) of pancreatic surgery reporting LOS. Analyses were conducted using a random-effects model with mean differences as the effect estimator for the continuous outcome LOS. RESULTS:In all, 186 RCTs published between 1994 and 2025, comprising 28 381 patients, were included. The mean LOS differed significantly by type of resection (P = 0.003) and by country (P < 0.001). Country remained a statistically significant factor after adjusting for readmission rate, year of study, and type of resection. The shortest LOS was observed in the USA, with a pooled value of 11 days (95% confidence interval (c.i.) 9.93 to 12.32) and the longest was seen in Japan, with a pooled value of 28 days (95% c.i. 25.60 to 31.67). Subgroup analysis of studies comparing minimally invasive and open surgery showed a mean LOS difference of 2 days (95% c.i. -2.79 to -0.85; prediction interval -7.70 to 4.06). However, this effect varied across countries, with mean LOS differences ranging from 1 to 6 days. CONCLUSION:LOS after pancreatic surgery exhibited substantial statistical heterogeneity based on country, the type of operation, and access. This highlights the importance of considering contextual factors when evaluating and comparing LOS as an outcome measure in pancreatic surgery.

OBJECTIVE:The International Study Group of Pancreatic Surgery (ISGPS) aimed to uniform the definition and classification of mortality following pancreatic resections, to guide strategies for reducing preventable deaths and standardize reporting. BACKGROUND:Reported rates of mortality after pancreatic surgery vary widely depending on patient comorbidities, case mix, and institutional expertise and resources. Conventional reporting lacks granularity and fails to capture the mechanisms leading to death. A standardized classification rooted in causal analysis may provide a more meaningful framework to appraise outcomes and design targeted interventions. METHODS:A systematic review of the literature, focusing on mortality rates, causes of death, and existing classification systems after pancreatectomy was conducted. A consensus definition and tripartite classification were developed through iterative discussions, revisions, and final approval by the ISGPS board members. RESULTS:Postpancreatectomy mortality (PPM) was defined as death occurring within 90 days of any pancreatic resection, directly or indirectly attributable to a surgical complication and retrospectively linked to it through root-cause analysis. Three categories were established: PPM 1, vascular/technical complexity-related mortality (15-30%); PPM 2, pancreatectomy-specific complication-related deaths, mainly due to postoperative pancreatic fistula (POPF) and secondary systemic deterioration (45-65%); and PPM 3, cardiopulmonary and cerebrovascular deaths (10-25%). Each category reflects distinct mechanisms, timing of onset, intervention windows, and opportunities for rescue. DISCUSSION:The proposed ISGPS classification of mortality enables the development of targeted strategies to reduce potentially preventable deaths and provides a more robust framework for the appraisal and benchmarking of surgical outcomes. Prospective validation is warranted to standardize this newly defined quality metric, ensuring its consistent use in future reporting and ultimately enhancing surgical quality and patient safety on a global scale.

BACKGROUND:Enhanced recovery after surgery (ERAS) pathways improve postoperative outcomes across surgical specialties, but the impact of ERAS compliance on outcomes after liver resection remains unclear. A retrospective cohort study of consecutive patients undergoing liver resection in an ERAS-certified centre was conducted to examine the association between overall and item-specific ERAS compliance and postoperative morbidity and length of hospital stay (LOS). METHODS:This retrospective cohort included elective liver resections performed between 2020 and 2024 at an ERAS-certified centre of excellence. ERAS compliance was prospectively recorded and categorized as high (≥ 70%) versus low/moderate (< 70%). Primary outcomes were any postoperative complication, major morbidity (Clavien-Dindo grade ≥ IIIa), and LOS; these were assessed by univariable and multivariable analyses, including a sensitivity analysis using an early compliance score excluding postoperative items. RESULTS:Data from 637 consecutive liver resections were analysed. Mean (standard deviation) overall ERAS compliance was 64.0 (10.2%) and remained stable over time. High compliance was associated with fewer complications (51% (104) versus 69.8% (303); odds ratio (OR) 0.45; 95% confidence interval (c.i.) 0.30 to 0.67; P < 0.001), lower major morbidity (7.25% (15) versus 12.8% (55); OR 0.25, 95% c.i. 0.10 to 0.64; P = 0.001), and shorter LOS (7.42 versus 10.62 days; mean difference -3.21 days; P < 0.001). In multivariable analyses, high overall compliance was associated with major morbidity (OR 0.16; 95% c.i. 0.04 to 0.56; P = 0.005). Minimally invasive surgery independently decreased overall complications (OR 0.41; 95% c.i. 0.21 to 0.75; P = 0.005), major morbidity (OR 0.13; 95% c.i. 0.01 to 0.66; P = 0.050), and LOS (β = -2.31 days; P = 0.020). In sensitivity analyses, high compliance remained associated with fewer complications (OR 0.62; 95% c.i. 0.40 to 0.96; P = 0.035). Higher intraoperative intravenous fluid volume independently predicted morbidity and prolonged LOS (P < 0.001). CONCLUSION:Higher ERAS compliance after liver resection is associated with lower severe morbidity and shorter LOS. Prioritizing potentially high-impact items may maximize recovery benefits.

Retroperitoneal sarcomas (RPS) pose major technical challenges because of their size, anatomical complexity, and need for multivisceral resection. We evaluated the feasibility of a standardized robotic approach for right- and left-sided retroperitoneal sarcoma (RPS) compartmental resection using the da Vinci Xi system in tumour-free human cadavers. In a two-phase IDEAL-D Stage 0 cadaveric study, two sarcoma surgeons first compared four trocar configurations in two cadavers to identify optimal port templates (Phase 1). Complete six-stage compartmental resection following a standardised protocol was then performed once on each side in a third cadaver (Phase 2). The confirmatory dissection was assessed with a 5-point anatomical reach rating per predefined landmark, an adapted System Usability Scale (SUS), and a structured safety surrogate log. Phase 1 yielded a horizontal suprasymphysial port template for the right side and an oblique xiphoid-to-right-lower-quadrant template for the left. In Phase 2, all six stages were completed bilaterally; all predefined landmarks were reached (pooled median reach 5/5, range 3–5; inter-rater agreement 90

Importance Total pancreatectomy (TP) is indicated for advanced pancreatic cancer or multifocal tumors. Furthermore, TP may be performed to avoid the risk of pancreatic fistula in selected patients to improve the perioperative risk profile. Objective To define reference values for TP based on a low-risk cohort treated at expert centers. Design, Setting, and Participants This multicenter study analyzed outcomes from patients undergoing primary TP for malignant or benign lesions from 25 international expert centers from January 2017 to November 2023. Low-risk patients undergoing TP (LR-TP) were without vascular resections or significant comorbidities. Exposures TP. Main Outcomes and Measures Twenty reference values were derived from the 75th or the 25th percentile of the median values of all centers. Outcomes of LR-TP were compared with a cohort of TP with vascular resection, TP due to high-risk pancreatic anastomosis, and the benchmark values for low-risk pancreatoduodenectomy. Results Of 994 patients, 333 (33.5%; median [IQR] age, 66 [58-72] years; 171 male [51.4%]) qualified as the LR-TP cohort. Reference values included blood loss (≤1000 mL), major complications (≤37%), 3-month postoperative mortality (<6%), and retrieved lymph nodes (≥29). Compared with TP with vascular resections, reference cutoffs were not met for major complications (51% vs LR-TP ≤37%) and 90-day mortality (11% vs LR-TP ≤6%). For TP due to high-risk anastomosis, failure to rescue rate (38% vs ≤6%) and 90-day mortality (11% vs LR-TP ≤6%) were not met. Compared with pancreatoduodenectomy, reference values for postoperative mortality were 3 times higher for LR-TP (≤2% vs ≤6%) and less for resected lymph nodes (≥16 vs ≥29). Conclusions and Relevance This case-control study provided global reference values for TP, indicating significantly higher postoperative morbidity and mortality compared with pancreatoduodenectomy. Perioperative morbidity of TP was especially increased in patients with vascular resections. These reference values can serve for quality control of pancreatic surgery.

Multimodal treatment with preoperative chemotherapy is increasingly used for locally advanced pancreatic cancer (LAPC) to enable surgical resection. However, the optimal time between the last cycle of preoperative chemotherapy and surgery remains unclear. This study aimed to evaluate the association between timing of surgery after preoperative chemotherapy and overall survival of patients with LAPC. Patients with LAPC who underwent pancreatic resection after preoperative chemotherapy between 2018 and 2023 were enrolled from a prospectively maintained database. The cohort was stratified by a predefined interval between the last cycle of chemotherapy and surgery (short interval: < 4 weeks vs long interval: ≥ 4 weeks). After preoperative chemotherapy, 169 patients underwent surgery, including 56 (33.1

Abstract The two mutually exchangeable ATPases SMARCA2 and SMARCA4 form the two catalytic subunits of a polymorphic family of SWI/SNF complexes. In both normal and malignant cells, they play a regulatory role in numerous essential cellular processes. For example, SWI/SNF affects the regulation of cell differentiation, programmed cell death, DNA repair, chromosome stability, signaling pathway crosstalk and cell metabolism. Topical interest in SMARCA4/SMARCA2 is due to the observation of their synthetic lethal relationship, potentially offering new therapeutic approaches. Targeting SMARCA4 deficient cancer cells with SMARCA2 inhibitors or degraders has resulted in significant growth inhibition in experimental systems and further agents are being tested in early clinical trials. To determine the prevalence of SMARCA2/SMARCA4 expression in cancer, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. SMARCA2 immunostaining was absent in 6.9%, weak in 8.0%, moderate in 18.3%, and strong in 66.8% of 12,253 interpretable tumors. SMARCA4 staining was absent in 0.7%, weak in 1.9%, moderate in 5.9%, and strong in 91.5% of 13,093 interpretable tumors. Remarkably, losses of SMARCA2 and SMARCA4 were strongly correlated. Of 91 SMARCA4 deficient tumors for which SMARCA2 data were also available, 28 (30.8%) did also show a complete loss of SMARCA2 expression. SMARCA2 deficiency was most commonly seen in Burkitt lymphoma (66.7%), endometrial carcinomas (up to 57.1%), rhabdoid tumors (50.0%) and ovarian carcinomas (up to 37.8%). SMARCA4 staining was predominantly lost in in neuroendocrine carcinomas (up to 25.0%), endometrioid carcinomas (up to 7.7%) and adenocarcinomas of the lung (7.5%). Absent or low SMARCA2 expression was significantly linked to unfavorable tumor phenotype in clear cell renal cell carcinoma, bladder cancer, and breast cancer while weak or absent SMARCA4 staining was linked to unfavorable tumor features in colorectal and clear cell renal cell carcinoma (p≤0.05). It is concluded, that SMARCA4 deficiency is a rather rare event in tumors, whereas SMARCA2 deficiency is much more common in many different tumor entities and is associated with unfavourable cancer characteristics in several tumor types. The frequent co-deficiency of SMARCA2 and SMARCA4 challenges the concept of a synthetic lethal relationship of these proteins in vivo. Citation Format: Nina Schraps, Anne Menz, Florian Lutz, Viktoria Chirico, Florian Viehweger, David Dum, Ria Schlichter, Andrea Hinsch, Fiete Gehrisch, Christoph Fraune, Christian Bernreuther, Seyma Büyücek, Martina Kluth, Claudia Hube-Magg, Katharina Möller, Viktor Reiswich, Andreas M. Luebke, Patrick Lebok, Baris Mercanoglu, Nathaniel Melling, Thilo Hackert, Guido Sauter, Maximilian Lennartz, Till S. Cauditz, Andreas H Marx, Ronald Simon, Stefan Steurer, Eike Burandt, Natalia Gorbokon, Maria Christina Tsourlakis, Sarah Minner, Till Krech, Morton Freytag. SMARCA2 and SMARCA4 expression in cancer: A tissue microarray study on 14,966 tumors from 134 different tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2980.

Robot-assisted pancreatoduodenectomy (RPD) is increasingly performed for cancer in the pancreatic head. Randomised evidence confirming its oncological safety and efficacy is lacking. The DIPLOMA-2x2 trial aims to compare the oncological safety of RPD versus OPD in terms of radicality (microscopically radical resection [R0] resection). We hypothesise that RPD is non-inferior to OPD in terms of radicality and superior regarding time to functional recovery. The DIPLOMA-2x2 trial is an investigator-initiated, international, multicentre, patient- and assessor-blinded randomised non-inferiority trial. The trial was conducted as a roll-over of the DIPLOMA-2 trial and includes 20 high-volume tertiary referral hospitals in 7 countries. Minimum surgeon’s experience is 60 RPD and 60 OPD, with a minimum annual centre volume of 30 RPD prior to trial initiation. Eligible patients are adults (≥18 years) with suspected or proven upfront resectable pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (DCC) without any vascular involvement. Participants are randomised in a 2:1 ratio to RPD or OPD, respectively, stratified by tumour indication (proven PDAC versus other) and preoperative pancreatic fistula risk (high versus low). In total, 413 patients will be included, of which 137 previously randomised in DIPLOMA-2 and 276 newly recruited in DIPLOMA-2x2. Patients are blinded up to postoperative day 5. Primary outcome is pathological R0-resection rate (pR0; >1 mm tumour clearance at surgical resection margins and anatomical surfaces, 0 mm clearance at anterior surface), tested for non-inferiority with a −7