Abstract Background Current imaging assessment for pancreatic cancer resectability demonstrates problematic inter-observer variability, with only fair-to-moderate agreement among experienced raters. Virtual reality technology offers stereoscopic three-dimensional visualization that may improve diagnostic accuracy and agreement. However, optimal visualization strategies for clinical adoption remain unclear. Methods Ten hepatopancreatobiliary surgeons from two high-volume centers were randomized 1:1 to assess twelve contrast-enhanced CT cases using either VR volumetric rendering or CSI. Primary outcomes included inter-rater agreement, diagnostic accuracy against expert reference standard, assessment time, and surgeon confidence. Statistical analysis employed Fleiss’ κ for inter-rater agreement and two-sided Mann–Whitney U tests on surgeon-level summary measures for between-group comparisons. Results CSI display on 2D screens achieved substantial inter-rater agreement for resectability assessment (κ = 0.609) while VR demonstrated only slight agreement (κ = 0.127). Diagnostic accuracy was superior with CSI (84.7% vs. 79.7%), with the most pronounced difference in resectability determination (83.3% vs. 58.3%, p = 0.033). VR users reported significantly lower confidence (4.85 ± 1.15 vs. 6.32 ± 0.77, p = 0.028). Assessment times were comparable between groups (median 313.5 s vs. 327.5 s, p = 1.00). Conclusions In this preliminary investigation, our VR visualization strategy demonstrated lower diagnostic accuracy and inter-rater agreement than CSI. However, prior studies suggest that VR systems employing alternative, hybrid visualization approaches may improve inter-rater agreement, indicating that visualization strategy, rather than VR technology per se, is the primary determinant of utility. Trial registration DRKS00033932 (German Clinical Trials Register), registered prospectively.

Background Painless icterus, elevated cholestatic parameters and cholangitis are among the most common symptoms associated with patients with perihilar cholangiocarcinoma. Preoperative optimization of these conditions is crucial and usually done through preoperative biliary stenting. Cholangitis is a frequent complication of biliary obstruction through tumor, and of stenting, but its impact on surgical and oncologic outcomes remains controversial. Methods We analyzed patients undergoing curative-intent surgery for perihilar cholangiocarcinoma. Clinical, laboratory, operative and pathological data were collected. Propensity score matching was performed to minimize baseline differences. Outcomes of patients with and without preoperative cholangitis were compared, with particular focus on survival in relation to preoperative biliary stenting. Result Of 305 patients, 204 remained after prospective score matching for baseline characteristics, including 108 with cholangitis and 96 without. Severe complications (Clavien Dindo IV-V) were more common in patients with cholangitis (25 % vs. 13.8%, p = 0.028). Median overall survival was significantly shorter in patients with cholangitis (2.05 vs. 3.03 years, p = 0.014), as was disease-free survival (1.26 vs. 2.21 years, p = 0.0006). Patients with both stenting and cholangitis had the poorest overall survival, when compared to those with stenting only (3.63 years) or those without stenting and without cholangitis (2.31 years, p = 0.03). Conclusion Preoperative cholangitis, particularly when combined with biliary stenting, is associated with significantly worse perioperative outcomes and long-term survival in patients with perihilar cholangiocarcinoma. These results underscore the importance of prophylactic antibiotics in the preoperative phase and call for strategies aimed at reducing stent-associated cholangitis.

Background: Achieving negative resection margins (R0) is considered essential for curative surgery in pancreatic ductal adenocarcinoma (PDAC). However, in the setting of complex multivisceral pancreatic resections, the prognostic relevance of margin status and its association with perioperative morbidity and long-term survival remain uncertain. We aimed to evaluate the association between resection margin status (R0 vs R1) and short-term and long-term outcomes in patients undergoing multivisceral pancreatic resections for PDAC. Methods: In this retrospective, international, multicentre cohort study, we analysed data from the largest global database of multivisceral pancreatic resections. Patients were recruited from multiple high-volume centres across several countries. Eligible participants were adults undergoing multivisceral pancreatic resection for histologically confirmed PDAC. Patients with incomplete key covariate data were excluded from propensity score matching (PSM). Clinical and pathological data were retrieved from institutional medical records and prospectively maintained databases.Propensity score matching (1:1) was performed using age, sex, body mass index, Charlson Comorbidity Index, ASA score, ECOG performance status, tumour stage, type of resection, and number of resected organs. The primary outcome was overall survival (OS). Secondary outcomes included 90-day mortality, perioperative morbidity (Clavien–Dindo classification), postoperative pancreatic fistula, delayed gastric emptying, reoperation, intraoperative complications, and ICU length of stay. Findings: After matching, 186 patients were analysed (93 R0; 93 R1). Ninety-day mortality was identical in both groups (6·5%). Rates of major morbidity, postoperative pancreatic fistula, delayed gastric emptying, reoperation, blood loss, operative time, and ICU stay were comparable between groups. Median OS was 23·6 months (95% CI 18·7–39·3) in the R0 group and 14·5 months (9·0–22·8) in the R1 group. After adjustment for residual imbalances, R1 resection was independently associated with poorer survival (HR 1·57, 95% CI 1·05–2·35; p=0·027). Interpretation: R0 resection in multivisceral pancreatic surgery is independently associated with improved long-term survival without increased perioperative morbidity or mortality. Margin-negative resection should remain the surgical goal in specialised high-expertise centres.

Human pancreatic islets are essential for studies in β-cell biology, cell transplantation, and tissue engineering, yet access to viable human islets remains limited because conventional isolation protocols primarily rely on whole pancreases from deceased donors. Surgical pancreatectomy specimens may represent an accessible alternative source, but factors influencing successful isolation and functional preservation remain poorly defined. In this study, we evaluated a standardized method for isolating human islets from pancreatic tissue obtained from surgical pancreatectomy specimens and investigated patient-, specimen-, and surgery-related factors affecting islet yield and functionality. Between March and October 2024, 50 consecutive islet isolations were performed from pancreatic specimens obtained during surgical resections. Following enzymatic digestion, tissue fractions were cultured for 24 h before handpicking of morphologically intact islets. Islet yield was quantified as islet equivalents (IEQ), and functional integrity was assessed by glucose-stimulated insulin secretion assays on culture days 1, 3, and 5. A mean yield of 6690 IEQ/g pancreatic tissue was obtained (range 0–56,500 IEQ/g). Exploratory analyses suggested potential associations between islet yield and factors such as younger patient age, shorter surgical duration, and preserved pancreatic parenchyma. However, these findings should be interpreted cautiously given the variability of the specimens and the exploratory design of the study. These findings support the feasibility of using surgical pancreatectomy specimens as an accessible source of functional human islets for experimental and translational research.

Abstract Background Chemoresistance in treatment of colorectal liver metastases (CRLM) poses a major challenge in preventing disease relapse, with up to 80% of patients developing drug resistance over the course of treatment. Proteomic signatures of responsive vs. non-responsive metastases can provide insights into functional expression patterns, potentially identifying biomarkers for therapy efficacy. Methods A total of 33 CRLM tissue samples from 31 patients were subjected to histopathological and proteomic analysis. The patients were included in the study after undergoing preoperative treatment (n = 28), including platinum-based chemotherapy (n = 19), non-platinum-based chemotherapy (n = 8), as well as targeted therapies (n = 20), or without preoperative therapy (n = 5). Based on Rubbia-Brandt criteria and vital tumor cell percentage, CRLM were categorized to major (MR), partial (PR) and no response (NR) groups. Proteomic analysis was conducted using label-free mass spectrometry (LFQ-MS), followed by clustering according to histological response and distinct treatment regimens. Results Proteomic analysis revealed significant differential protein expression of 607 proteins linked to distinct histopathological response types. CRLM responsive to chemotherapy displayed marked enrichment (p ≤ 0.01) in pathways associated with immune infiltration, ECM matrix organization, the complement system, and apolipoprotein-associated processes, indicative of distinct stromal and immune invasion patterns with multimodal importance of cell adhesion proteins. In contrast, attenuated expression of proteins enriched in pathways of mitochondrial translation initiation, elongation and termination was detectable. Conclusion CRLM exhibited distinct proteomic phenotypes based on their histopathological response to preoperative systemic therapy largely independent of chemotherapy regimens. This proteomic profiling establishes a foundation for identifying critical biomarker profiles by nominating protein markers for major chemotherapy response.

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors that exhibit a range of biological behaviors, from indolent to aggressive. Identifying prognostic factors for pNETs is essential for risk stratification and personalized treatment planning. Clinicopathological data of stage I to III patients who underwent pancreatic resection and were treated for pNET at an ENETS Center of Excellence from 2009 to 2023 were analyzed retrospectively. 89 pNET patients were included (45 female, 44 male). Proximal pNETs had higher proportions of lymph node metastases (48.4

OBJECTIVES:MR elastography (MRE) offers valuable mechanical tissue characterization for clinical diagnosis. However, conventional single-driver, single-frequency MRE systems are often limited by insufficient coverage of deep-seated organs like the pancreas. This study investigates whether multiplex MRE using multiple drivers and vibration frequencies can overcome these limitations. MATERIALS AND METHODS:This prospective study used single-shot spin-echo MRE in 18 healthy volunteers (mean age 30±8 y) targeting the liver, pancreas, kidneys, and spleen. Each healthy volunteer underwent 16 MRE examinations with different sets of 4 vibration frequencies in the range of 30 to 60 Hz and 4 driver combinations, and an additional null experiment without vibrations. In addition, a cohort of 14 patients with pancreatic ductal adenocarcinoma (PDAC, mean age 57±15 y) were retrospectively assessed. The quality of shear-wave fields and stiffness maps were assessed in terms of displacement amplitudes and image sharpness. RESULTS:In healthy volunteers, abdominal coverage with displacement amplitudes above the pre-determined noise level of 4 µm varied among the MRE investigated: 24.2% (0.0% to 56.2%, single-driver at 60 Hz), 66.9% (24.8% to 97.7%, single-driver at 30 to 60 Hz), 70.2% (0.0% to 92.5%, multi-driver at 60 Hz), and 99.9% (89.4% to 100%, multi-driver at 30 to 60 Hz). In the pancreas, more than 60% coverage was achieved in all subjects using 4 drivers and multiple frequencies. This was achieved in only 2 of 18 subjects (11%) using single-driver/single-frequency MRE. Superficial organs were adequately assessed with all configurations. In patients with PDAC, multi-driver MRE at 30 to 60 Hz achieved 99.1% (91.4% to 100%) coverage of the pancreas and 96.3% (63.1% to 100%) abdominal coverage, suggesting that tomographic stiffness mapping is clinically feasible. CONCLUSION:MRE with at least 4 drivers and multiple vibration frequencies in the range of 30 to 60 Hz enables tomographic mapping of tissue stiffness across the entire abdomen, including the pancreas. Our results thus indicate that multiplex MRE is a promising approach for generating detailed images of abdominal stiffness that can improve clinical diagnosis of abdominal and pancreatic diseases.

Postoperative hemorrhagic complications in pancreatic surgery are classified according to the International Study Group for Pancreatic Surgery (ISGPS). However, following total pancreatectomy, the predominant bleeding causes associated with pancreatic fistula or insufficiency of the pancreatico-enteric anastomosis are eliminated. The objective of this study is to examine bleeding sources following total pancreatectomy, and propose a novel classification, termed Post-Total Pancreatectomy Hemorrhage (PTPH). An overall of 195 patients was included and reviewed for baseline characteristics, comorbidities, intraoperative findings, perioperative coagulation profiles, and postoperative courses. Applicability of the ISGPS classification to PTPH was critically assessed with respect to the existing criteria: timely onset, location and cause, and severity. Subgroups were defined with regard to bleeding sources including erosion, surgical, gastrointestinal, and diffuse bleeding. Furthermore, we developed a severity index to enhance objectivity. Thirty-five of the patients experienced hemorrhagic complications. Timely onset and our severity index corresponded significantly with the bleeding source. The ISGPS classification, although widely utilized in pancreatic surgery, does not fully account for the bleeding complications associated with total pancreatectomy. Our proposed classification for PTPH introduces a more granular and clinically relevant framework, with clearly delineated subgroups based on source, and an innovative severity index.

BACKGROUND:Comprehensive preoperative risk stratification is essential for improving perioperative outcomes and guiding informed decisions in general surgery (GS). However, data scarcity remains a key challenge to developing robust, high-dimensional artificial intelligence (AI) models. To address this data barrier in surgical AI, transfer learning (TL) enables neural networks (NNs) to transfer and adapt knowledge from pretrained source models to new domains with critically limited data availability. METHODS:This multicenter study included patients undergoing advanced GS at three tertiary centers between 2015 and 2023. Multiple large-scale source models for 90-day mortality prediction were trained on 85 preoperative parameters. Subsequently, organ-specific fine-tuning was performed for esophageal, liver, pancreatic, and colorectal surgery individually. TL models were benchmarked against standard ML models and conventional risk scores using the area under the receiver-operating characteristic curve (AUROC), precision-recall curve (AUPRC), and F1-score, including 95% confidence intervals. Feature analyses were performed for each NN to investigate and compare model interpretability. RESULTS:14 922 patients (mean [SD] age: 58.5 [16.1] years) were included. Conventional ML achieved AUROCs of 0.75 (0.72-0.79; esophageal surgery), 0.80 (0.79-0.82; liver surgery), 0.73 (0.71-0.76; pancreatic surgery), and 0.92 (0.92-0.92; colorectal surgery) with corresponding AUPRCs reaching 0.37 (0.33-0.43), 0.30 (0.29-0.31), 0.29 (0.24-0.34), and 0.57 (0.56-0.58), respectively. TL significantly improved AUPRCs by 38% in esophageal (0.54 [0.51-0.58], P < 0.001), 14% in liver (0.34 [0.32-0.36], P < 0.001), and 8% in pancreatic surgery (0.31 [0.28-0.37], P < 0.001). Patient age and the Charlson Comorbidity Index (CCI) consistently emerged as the highest-weight features across all TL models. All NNs outperformed the American Society of Anesthesiologists Physical Status and CCI as conventional risk scores in predicting mortality. CONCLUSIONS:Machine learning outperforms conventional risk modeling in preoperative mortality prediction. TL can significantly enhance model performance in surgical domains with limited data availability, offering a promising approach to overcome persisting data constraints for AI in surgery.

The origin of mucinous cystic neoplasms (MCNs) remains a major challenge in hepato‐pancreato‐biliary pathology. These cystic tumors are defined by their mucinous epithelium and ovarian‐like stroma, with an estimated 10% risk of progression to invasive carcinoma. The origin of the ovarian‐like stroma remains a subject of debate. In this study, we conducted immunohistochemical profiling, targeted DNA sequencing, and genome‐wide DNA methylation analysis on a cohort of 15 pancreatic MCNs (MCN‐P) and six hepatic MCNs (MCN‐L). Using immunohistochemistry and targeted DNA sequencing, we unequivocally established the diagnosis of MCN. Unsupervised DNA methylation profile analysis of reference classes of pancreatic neoplasms (11 entities and normal pancreatic tissue from 224 unique samples) revealed that MCN‐P predominantly forms a distinct group. In the DNA methylation landscape of liver tumors, encompassing five tumor types and normal bile duct tissue from 136 unique samples, MCN‐L demonstrated a specific methylation profile when compared with all other entities. Furthermore, within the DNA methylation landscape of ovarian tumors – featuring five tumor types, normal Fallopian tube, and normal ovarian tissue from 90 unique samples – we found that both MCN‐P and MCN‐L grouped with mucinous ovarian carcinoma and mucinous borderline ovarian tumors (mBOTs). Notably, low‐grade MCNs exhibited greater DNA methylation similarities to mBOTs, while high‐grade or invasive MCNs were primarily associated with mucinous ovarian carcinomas. When analyzing all samples together (19 tumor types and four normal tissue types, n = 430), MCNs similarly grouped with mucinous ovarian tumors and normal ovarian tissue. Additionally, in a network analysis of differentially methylated probes, MCN‐P and MCN‐L share significant methylation traits, closely resembling mucinous ovarian tumors. In conclusion, our findings highlight that MCN‐P and MCN‐L are distinct entities in the landscape of pancreatic and hepatic tumors and show DNA methylation profile similarities with mucinous ovarian tumors, suggesting a potential common origin. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

OBJECTIVE:To evaluate short-term outcomes and identify predictors of morbidity and mortality following multivisceral oncologic resections involving the pancreas. SUMMARY BACKGROUND DATA:Multivisceral resections including the pancreas are required for locally advanced abdominal malignancies but are associated with considerable perioperative risk. While smaller series suggest acceptable outcomes in selected patients, large-scale international data are lacking to guide surgical decision-making and risk stratification. METHODS:This was a retrospective cohort study of 1,283 patients from 31 international centers who underwent multivisceral oncologic resections involving the pancreas. Patient demographics, tumor characteristics, operative details, and 90-day postoperative outcomes were analyzed. RESULTS:The cohort had a mean age of 64.7 years, and 54.7% were male. Distal pancreatectomy was the most frequent procedure (60.5%), and R0 resection was achieved in 60.9% of cases. Ninety-day mortality was 6.9%, highest in patients with gastric adenocarcinoma (16.7%). Major complications (Clavien-Dindo grade III-V) occurred in 34.4% of patients. Higher ASA classification and open surgical approach were independently associated with increased morbidity and mortality. Prolonged operative time was associated with morbidity only. Female gender and treatment at high-volume centers were protective. In patients with pancreatic tumors, resection involving the colon (OR 1.78, p<0.001), stomach (OR 1.33, p = 0.042), or three or more organs (OR 1.75, p = 0.006) significantly increased complication rates. CONCLUSIONS:Multivisceral resections involving the pancreas are associated with relevant perioperative risk. Optimizing patient selection, favoring minimally invasive techniques when feasible in selected patients, and centralizing care to high-volume centers may help improve outcomes for these complex surgical procedures.

BACKGROUND:Postoperative pancreatic fistula (POPF) remains a prevalent complication after left-sided pancreatectomy. Interventional treatment is regularly required and relies on interdisciplinary concepts, including interventional radiology and endoscopy. Evidence on the correct indication and clinical algorithms for available treatment modalities are needed. METHODS:During a 5-year observational period, we followed the clinical courses of 200 patients after left-sided pancreatectomy. Patients who fulfilled clinical and radiographic criteria for interventionally-relevant(IR-) POPF were identified. Interventional treatment groups were stratified via established step-up concepts for descriptive analyses and via a decision-based algorithm for comparative analyses. We used a Multi-State Time-to-Event Model (MSM) to assess clinical resolution efficacy. RESULTS:Following surgery, patients with IR-POPF needed multiple (58.2 %) and multimodal (49.4 %) interventions to achieve final resolution. Technical success rates were higher in ED (57.7 %) versus PD (32.7 %), and resulted in earlier resolution (8.4d, 95%C [5.5-11.2d]) when compared to the PD group (23.4d, 95%CI[2.8-17.9d]). At any given time, probability of reaching clinical resolution were higher for ED in multifaceted MSM analysis (HR 1.39, 95%CI[0.854, 2.25]). CONCLUSION:The present study highlights the importance of endoscopy-guided drainage placement after left-sided pancreatic resection. CRP value appeared to be a single objectifiable parameter for optimized treatment allocation.

Objectives: MR elastography (MRE) offers valuable mechanical tissue characterization, however, in deep abdominal organs like the pancreas conventional single-driver, single-frequency approaches often fail. This study evaluates whether multiplex MRE using multiple drivers and vibration frequencies can overcome these limitations. Methods: This study used single-shot spin-echo MRE in 18 healthy volunteers targeting the liver, pancreas, kidneys, and spleen. Each healthy volunteer underwent 16 MRE examinations with different sets of four vibration frequencies (30-60 Hz) and four driver combinations, and an additional null experiment without vibrations. Further, a cohort of 14 patients with pancreatic ductal adenocarcinoma (PDAC) were retrospectively assessed. The quality of shear-wave fields and stiffness maps was assessed by displacement amplitudes and image sharpness. Results: In healthy volunteers, abdominal coverage with displacement amplitudes above the pre-determined noise level of 4 μm varied between MRE configurations: 24.2 Conclusion: MRE with four drivers and multiple vibration frequencies between 30-60 Hz enables tomographic mapping of tissue stiffness across the entire abdomen, including the pancreas. Multiplex MRE offers a promising approach for generating detailed images of abdominal stiffness, potentially enhancing clinical diagnostics for abdominal and pancreatic diseases.

Background:Postoperative pancreatic fistula (POPF) is a major complication after pancreatic resection. This systematic review and meta-analysis investigated the impact of neoadjuvant therapy (NAT) on POPF rates after pancreatoduodenectomy (Whipple procedure) and distal pancreatectomy. Methods:A systematic search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Central Register of Controlled Trials was conducted for studies published since 2016 using the updated International Study Group of Pancreatic Fistula (ISGPF) definition for POPF. Random-effects models were used to pool data. Results:Thirty studies (22,048 patients) were included. Of those, 24 were comparative studies between neoadjuvant and upfront surgery (UPS) groups, while 6 reported POPF rates only in the neoadjuvant group. NAT significantly reduced POPF rates after Whipple procedure [risk ratio (RR) 0.44, 95% confidence intervals (CI): 0.38-0.52, P<0.01]. A harder pancreatic texture was more common after NAT compared to UPS (RR 1.27, 95% CI: 1.23-1.32, P<0.001). There were no significant differences between the neoadjuvant and upfront surgery groups regarding pancreatic duct size or body mass index (BMI). Conclusions:NAT reduces POPF after Whipple procedure, likely by altering pancreatic texture. The exact mechanisms by which the pancreas becomes harder during neoadjuvant treatment remain unclear. This finding could be implemented to improve surgical outcomes in patients with a soft pancreas. However, accurately predicting tumor response to NAT is a prerequisite for such an approach to avoid potential disease progression. Advances in personalized medicine, where tumor response could be predicted, offer hope for tailoring treatment strategies and maximizing outcomes.

BACKGROUND:This study evaluates the feasibility of a novel deep learning-accelerated half-fourier single-shot turbo spin-echo sequence (HASTE-DL) compared to the conventional HASTE sequence (HASTES) in postoperative single-sequence MRI for the detection of fluid collections following abdominal surgery. As small fluid collections are difficult to visualize using other techniques, HASTE-DL may offer particular advantages in this clinical context. MATERIALS AND METHODS:A retrospective analysis was conducted on 76 patients (mean age 65±11.69 years) who underwent abdominal MRI for suspected septic foci following abdominal surgery. Imaging was performed using 3-T MRI scanners, and both sequences were analyzed in terms of image quality, contrast, sharpness, and artifact presence. Quantitative assessments focused on fluid collection detectability, while qualitative assessments evaluated visualization of critical structures. Inter-reader agreement was measured using Cohen's kappa coefficient, and statistical significance was determined with the Mann-Whitney U test. RESULTS:HASTE-DL achieved a 46% reduction in scan time compared to HASTES, while significantly improving overall image quality (p<0.001), contrast (p<0.001), and sharpness (p<0.001). The inter-reader agreement for HASTE-DL was excellent (κ=0.960), with perfect agreement on overall image quality and fluid collection detection (κ=1.0). Fluid detectability and characterization scores were higher for HASTE-DL, and visualization of critical structures was significantly enhanced (p<0.001). No relevant artifacts were observed in either sequence. CONCLUSION:HASTE-DL offers superior image quality, improved visualization of critical structures, such as drainages, vessels, bile and pancreatic ducts, and reduced acquisition time, making it an effective alternative to the standard HASTE sequence, and a promising complementary tool in the postoperative imaging workflow.

The prevalence of asymptomatic pancreatic cysts is increasing due to advances in imaging techniques. Among these, intraductal papillary mucinous neoplasms (IPMNs) are most common, with potential for malignant transformation, often necessitating close follow-up. This study evaluates novel MRI techniques for the assessment of IPMN. From May to December 2023, 59 patients undergoing abdominal MRI were retrospectively enrolled. Examinations were conducted on 3-Tesla scanners using a Deep-Learning Accelerated Half-Fourier Single-Shot Turbo Spin-Echo (HASTEDL) and standard HASTE (HASTES) sequence. Two readers assessed minimum detectable lesion size and lesion-to-parenchyma contrast quantitatively, and qualitative assessments focused on image quality. Statistical analyses included the Wilcoxon signed-rank and chi-squared tests. HASTEDL demonstrated superior overall image quality (p < 0.001), with higher sharpness and contrast ratings (p < 0.001, p = 0.112). HASTEDL showed enhanced conspicuity of IPMN (p < 0.001) and lymph nodes (p < 0.001), with more frequent visualization of IPMN communication with the pancreatic duct (p < 0.001). Visualization of complex features (dilated pancreatic duct, septa, and mural nodules) was superior in HASTEDL (p < 0.001). The minimum detectable cyst size was significantly smaller for HASTEDL (4.17 mm ± 3.00 vs. 5.51 mm ± 4.75; p < 0.001). Inter-reader agreement was for (к 0.936) for HASTEDL, slightly lower (к 0.885) for HASTES. HASTEDL in IPMN imaging provides superior image quality and significantly reduced scan times. Given the increasing prevalence of IPMN and the ensuing clinical need for fast and precise imaging, HASTEDL improves the availability and quality of patient care. Question Are there advantages of deep-learning-accelerated MRI in imaging and assessing intraductal papillary mucinous neoplasms (IPMN)? Findings Deep-Learning Accelerated Half-Fourier Single-Shot Turbo Spin-Echo (HASTEDL) demonstrated superior image quality, improved conspicuity of “worrisome features” and detection of smaller cysts, with significantly reduced scan times. Clinical relevance HASTEDL provides faster, high-quality MRI imaging, enabling improved diagnostic accuracy and timely risk stratification for IPMN, potentially enhancing patient care and addressing the growing clinical demand for efficient imaging of IPMN.

Background: Pancreatic adenocarcinoma (PDAC) is still a complex, devastating disease. Cachexia symptoms frequently impair patient survival. This accompanying syndrome is commonly diagnosed late, when clinical signs become evident. Early diagnosis using conventional measurement methods is often difficult, and the discrimination of this disease from cancer progression is challenging and often overlaps. The aim of this study was to analyze whether conventional nutritional assessments or laboratory biomarkers are better predictive tools for the early detection of patients at risk of reduced survival. Methods: We analyzed a prospective predefined cohort of 182 patients with gastrointestinal cancer, 120 patients with PDAC and—as controls—62 patients with other gastrointestinal adenocarcinoma (oAC), from whom we have sufficient data of protocol-defined conventional nutritional assessments, clinical data, and specific laboratory parameters. Results: at the time of tumor diagnosis, high inflammatory biomarkers (c-reactive protein (CRP), interleukin-6 (IL-6)) and albumin serum levels were associated with impaired OS in PDAC patients, but not in patients with oAC. Hemoglobin, body mass index (BMI), and bioelectrical assessments alone did not have a prognostic impact at the time of diagnosis. In a multivariate analysis, only CRP (HR 1.91 (1.25–2.92), p = 0.003) was found to be an independent prognostic factor in PDAC patients. Over the course of the disease in PDAC patients, inflammatory biomarkers, albumin, hemoglobin, and bioelectrical assessments were associated with impaired OS. In multivariate testing, CRP (HR 2.21 (1.38–3.55), p < 0.001) and albumin (HR 1.71 (1.05–2.77), p = 0.030) were found to be independent prognostic factors in PDAC patients. Conclusion: Specifically for PDAC patients, high inflammatory index and albumin serum levels potentially represent a sufficient early surrogate marker to detect patients at high risk of impaired OS better than complex conventional methods. These findings could help to identify patients who may benefit from early therapeutic interventions.

Pancreatic ductal adenocarcinoma (PDAC) remains a particularly aggressive disease with few effective treatments. The PDAC tumor immune microenvironment (TIME) is known to be immune suppressive. Oncolytic viruses can increase tumor immunogenicity via immunogenic cell death (ICD). We focused on tumor-selective (vvDD) and cytokine-armed Western-reserve vaccinia viruses (vvDD-IL2 and vvDD-IL15) and infected carcinoma cell lines as well as patient-derived primary PDAC cells. In co-culture experiments, we investigated the cytotoxic response and the activation of human natural killer (NK). Infection and virus replication were assessed by measuring virus encoded YFP. We then analyzed intracellular signaling processes and oncolysis via in-depth proteomic analysis, immunoblotting and TUNEL assay. Following the co-culture of mock or virus infected carcinoma cell lines with allogenic PBMCs or NK cell lines, CD56+ NK cells were analyzed with respect to their activation, cytotoxicity and effector function. Both, dose- and time-dependent release of danger signals following infection were measured. Viruses effectively entered PDAC cells, emitted YFP signals and resulted in concomitant oncolysis. The proteome showed reprogramming of normally active core signaling pathways in PDAC (e.g., MAPK-ERK signaling). Danger-associated molecular patterns were released upon infection and stimulated co-cultured NK cells for enhanced effector cytotoxicity. NK cell subtyping revealed enhanced numbers and activation of a rare CD56dimCD16dim population. Tumor cell killing was primarily triggered via Fas ligands rather than granule release, resulting in marked apoptosis. Overall, the cytokine-armed vaccinia viruses induced NK cell activation and enhanced cytotoxicity toward human PDAC cells in vitro. We could show that cytokine-armed virus targets the carcinoma cells and thus has great potential to modulate the TIME in PDAC.

Background Acute necrotizing pancreatitis is still related to high morbidity and mortality rates. Minimal-invasive treatment options, such as endoscopic necrosectomy, may decrease peri-interventional morbidity and mortality. This study aims to compare the initial operative with endoscopic treatment on long-term parameters, such as endocrine and exocrine functionality, as well as mortality and recurrence rates. Methods We included 114 patients, of whom 69 were treated with initial endoscopy and 45 by initial surgery. Both groups were further assessed for peri-interventional and long-term parameters. Results In the post-interventional phase, patients in the group of initial surgical treatment (IST) showed significantly higher rates of renal insufficiency ( p < 0.001) and dependency on invasive ventilation ( p < 0.001). The in-house mortality was higher in the surgical group, with 22% vs. 10.1% in the group of patients following initial endoscopic treatment (IET; p = 0.077). In long-term follow-up, the overall mortality was 45% for IST and 31.3% for IET ( p = 0.156). The overall in-hospital stay and intensive care unit (ICU) stay were significantly shorter after IET ( p < 0.001). In long-term follow-up, the prevalence of endocrine insufficiency was 50% after IST and 61.7% after IET ( p = 0.281). 57.1% of the patients following IST and 16.4% of the patients following IET had persistent exocrine insufficiency at that point ( p = < 0.001). 8.9% of the IET and 27.6% of the IST patients showed recurrence of acute pancreatitis ( p = 0.023) in the long-term phase. Conclusion In our cohort, an endoscopic step-up approach led to a reduced in-hospital stay and peri-interventional morbidity. The endocrine function appeared comparable in both groups, whereas the exocrine insufficiency seemed to recover in the endoscopic group in the long-term phase. These findings advocate for a preference for endoscopic treatment of acute necrotizing pancreatitis whenever feasible.