Search Results (16)

Cancer progression is driven not only by biochemical signals but also by abnormal physical forces within a stiffened tumor microenvironment. This review re-examines the anticancer compound sulforaphane (SFN) through the integrative lens of tumor biomechanics. We propose SFN functions as a “mechano-modulator,” whose pleiotropic effects converge to disrupt pro-invasive mechanotransduction. SFN targets key force-sensitive pathways (e.g., YAP/TEAD, Rho/ROCK), destabilizes invasion machinery (cytoskeleton, invadopodia), and promotes tissue-level changes such as extracellular matrix remodeling. While preclinical evidence for this mechano-modulatory role is compelling, this perspective also highlights the critical need for clinical validation and discusses the key translational challenges. By systematically linking SFN’s molecular actions to the biophysics of tumor progression, this synthesis provides a novel framework for understanding its efficacy and outlines a rational path for its future development as a mechano-inspired therapeutic. Full article

Background and Objectives: Pancreatoduodenectomy (PD) is the primary treatment for patients with resectable, non-metastatic pancreatic adenocarcinoma and periampullary tumors. Although surgical methods and perioperative management have improved, the procedure still carries a high risk of complications, with postoperative pancreatic fistula (POPF) being the most significant. This study focuses on identifying current risk factors for POPF after PD in a single HPB center. Materials and Methods: We retrospectively analyzed prospectively collected data from patients undergoing PD in our department between October 2018 and April 2024. Data included demographics, comorbidities, lifestyle factors, preoperative tests (bilirubin, CA19-9, HbA1c), intraoperative variables (pancreatic texture, duct diameter), and postoperative outcomes. POPF was classified using the International Study Group of Pancreatic Surgery (ISGPS) criteria. Univariate and multivariate logistic regression analyses were performed. Results: A total of 118 patients underwent PD (82 males, 36 females; mean age 67 (45–85) years; mean body mass index (BMI) 26.6 kg/m²). POPF occurred in 37 patients (31%), with 27 Grade B (23%) and 10 Grade C (9%). The 30- and 90-day mortality rates were 5% and 12.7%, respectively. Univariate analysis showed associations between POPF and soft pancreas (p = 0.018), c-reactive protein (CRP) on postoperative day (POD) 5 (p = 0.004), and serum amylase on POD 0 (p = 0.008). Diabetes mellitus was associated with a lower incidence of POPF (p = 0.014). Multivariate analysis confirmed CRP on POD 5 (OR 1.007, p = 0.025) and DM (OR 0.254, p = 0.015), as independent factors. ROC analysis identified POD 0 amylase >113.5 U/L (AUC 0.717) and POD 5 CRP >125.3 mg/dL (AUC 0.669) as predictive values. Conclusions: POPF remains an important complication after PD. CRP > 126 mg/dL on POD 5 was associated with POPF and may serve as an adjunctive signal to guide further assessment, including imaging. The observed inverse association with diabetes mellitus is hypothesis-generating and should be interpreted cautiously, considering potential confounding and the influence of center volume, surgeon heterogeneity, and institutional protocols. Full article

Background: Timely identification of individuals at elevated risk for gastric cancer (GC) within routine care could enable earlier endoscopy and referral. We posit that cancers within the gastrointestinal/hepatopancreatobiliary spectrum share signals that can be leveraged via transfer learning on electronic health records (EHRs) variables. Methods: We developed a cross-cancer transfer learning framework (TransferGC) on structured EHR data from the MIMIC-IV database, including 508 GC cases in the target cohort, that pretrains on non-gastric gastrointestinal/hepatopancreatobiliary cancers (colorectal, esophageal, liver, pancreatic) and then adapts to GC using only structured variables. We compared transfer variants against strong non-transfer baselines (logistic regression, XGBoost, architecturally matched multilayer perceptron), with area under the receiver operating characteristic curve (AUROC) and average precision (AP) as primary endpoints and F1 and sensitivity/specificity as secondary endpoints. Results: In the full-label setting, Transfer achieved AUROC $0.854$ and AP $0.600$, outperforming logistic regression (LR), extreme gradient boosting (XGB) and improving over the scratch multilayer perceptron (MLP) in AUROC ($+0.024$) and F1 ($+0.027$), while AP was essentially tied (Transfer $0.600$ vs. MLP $0.603$). As GC labels were reduced, Transfer maintained the strongest overall performance. Conclusions: Cross-cancer transfer on structured EHR data suggests a sample-efficient route to GC risk modeling under label scarcity. However, because all models were developed and evaluated using a single-center inpatient dataset, external validation on multi-center and outpatient cohorts will be essential to establish generalizability before deployment. If confirmed in future studies, the proposed framework could be integrated into EHR-based triage and clinical decision support workflows to flag patients at elevated GC risk for timely endoscopy and specialist referral. Full article

Iatrogenic bile duct injury (IBDI) constitutes a major complication of cholecystectomy. The optimal timing, method, and setting for definitive repair remain subjects of debate. This study aimed to systematically evaluate management strategies, timing of repair, and prognostic factors influencing postoperative outcomes following IBDI. A systematic review and meta-analysis were conducted in accordance with PRISMA and MOOSE guidelines (PROSPERO CRD420251003227). PubMed and the Cochrane Library were searched through March 2025. Eligible randomized trials and cohort studies reporting management outcomes were included. Data extraction and quality assessment were performed independently. Pooled analyses were conducted using random-effects models. Twenty-eight studies (2 randomized trials, 24 cohort studies, 2 systematic reviews) involving >18,000 patients were analyzed. Surgical repair achieved higher success than endoscopic therapy (92.6% vs. 76.1%; RR 1.22, 95% CI 1.10–1.35) and reduced stricture risk (RR 0.24, 95% CI 0.15–0.38). Roux-en-Y hepaticojejunostomy provided durable outcomes (success 83.5%; stricture 8.9%). Early (<2 weeks) or delayed (>6 weeks) repair after sepsis control was associated with lower morbidity (9–11%) compared with intermediate repair (2–6 weeks). Referral to hepatopancreatobiliary (HPB) centers reduced complications (RR 0.32, 95% CI 0.23–0.46). Overall morbidity and mortality were 22.7% and 2.9%. Outcomes following IBDI are determined primarily by surgical expertise and patient stability rather than timing alone. In optimized patients, both early and delayed reconstruction are safe and effective, whereas intermediate repair and non-specialist interventions increase risk. Timely referral to HPB centers should be considered standard practice. Full article

Background: Hepatopancreatobiliary (HPB) surgery is among the most complex domains in oncologic care, where decisions entail significant risk–benefit considerations. Artificial intelligence (AI) has emerged as a promising tool for improving individualized decision-making through enhanced risk stratification, complication prediction, and survival modeling. However, its role in HPB oncologic surgery has not been comprehensively assessed. Methods: This systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO ID: CRD420251114173. A comprehensive search across six databases was performed through 30 May 2025. Eligible studies evaluated AI applications in risk–benefit assessment in HPB cancer surgery. Inclusion criteria encompassed peer-reviewed, English-language studies involving human s ubjects. Two independent reviewers conducted study selection, data extraction, and quality appraisal. Results: Thirteen studies published between 2020 and 2024 met the inclusion criteria. Most studies employed retrospective designs with sample sizes ranging from small institutional cohorts to large national databases. AI models were developed for cancer risk prediction (n = 9), postoperative complication modeling (n = 4), and survival prediction (n = 3). Common algorithms included Random Forest, XGBoost, Decision Trees, Artificial Neural Networks, and Transformer-based models. While internal performance metrics were generally favorable, external validation was reported in only five studies, and calibration metrics were often lacking. Integration into clinical workflows was described in just two studies. No study addressed cost-effectiveness or patient perspectives. Overall risk of bias was moderate to high, primarily due to retrospective designs and incomplete reporting. Conclusions: AI demonstrates early promise in augmenting risk–benefit assessment for HPB oncologic surgery, particularly in predictive modeling. However, its clinical utility remains limited by methodological weaknesses and a lack of real-world integration. Future research should focus on prospective, multicenter validation, standardized reporting, clinical implementation, cost-effectiveness analysis, and the incorporation of patient-centered outcomes. Full article

Background: Hepato-pancreato-biliary (HPB) surgery involves operations that depend heavily on precise imaging, careful planning, and intraoperative decision-making. The rapid emergence of artificial intelligence (AI) and digital tools has assisted in these domains. Methods: We performed a PRISMA-guided systematic review (searches through June 2025) of AI/digital technologies applied to HPB surgical care, including novel models such as machine learning, deep learning, radiomics, augmented/mixed reality, and computer vision. Our focus was for eligible studies to address imaging interpretation, preoperative planning, intraoperative guidance, or outcome prediction. Results: In total, 38 studies met inclusion criteria. Imaging models constructed with AI showed high diagnostic performance for lesion detection and classification (commonly AUC ~0.80–0.98). Moreover, risk models using machine learning frequently exceeded traditional scores for predicting postoperative complications (e.g., pancreatic fistula). AI-assisted three-dimensional visual reconstructions enhanced anatomical understanding for preoperative planning, while augmented and mixed-reality systems enabled real-time intraoperative navigation in pilot series. Computer-vision systems recognized critical intraoperative landmarks (e.g., critical view of safety) and detected hazards such as bleeding in near real time. Most of the studies included were retrospective, single-center, or feasibility designs, with limited external validation. Conclusions: The usage of AI and digital tools show promising results across the HPB pathway—from preoperative diagnostics to intraoperative safety and guidance. The evidence to date supports technical feasibility and suggests clinical benefit, but routine adoption and further conclusions should await prospective, multicenter validation and consistent reporting. With continued refinement, multidisciplinary collaboration, appropriate cost effectiveness, and attention to ethics and implementation, these technologies could improve the precision, safety, and outcomes of HPB surgery. Full article

Background/Objectives: Like many other countries, the management of pancreatic cancer in Spain has developed in a fragmented manner. This study analyzes clinical outcomes related to patient volume at different centers after left pancreatectomy (LP). Our goal is to determine whether our practices align with the standards established in the literature and assess whether centralization’s advantages significantly outweigh its disadvantages. Methods: The SPANDISPAN Project (SPANish DIStal PANcreatectomy) is an observational, prospective, multicenter study focused on LP conducted in Spanish Hepato-Pancreato-Biliary (HPB) Surgery Units from 1 February 2022 to 31 January 2023. HPB units were defined as high volume if they performed more than 10 LPs annually. Results: This study included 313 patients who underwent LP at 42 centers across Spain over the course of a year. A total of 40.3% of the procedures were performed in high-volume centers. Significant differences in preoperative variables were only observed in ASA scores, which were higher in the high-volume group. Intraoperatively, minimally invasive surgical techniques were performed more frequently in high-volume centers. Postoperatively, the administration of somatostatin, major complications, and B and C postoperative pancreatic fistula (POPF) were more frequent in low-volume hospitals. Conclusions: The findings revealed that high-volume centers had a higher rate of minimally invasive surgery, lower intraoperative bleeding, fewer complications, and reduced POPFs compared to low-volume centers. However, it is important to note that low-volume centers still demonstrated acceptable outcomes. Thus, the selective referral of more complex laparoscopic procedures could initiate a gradual centralization of surgical practices. Full article

Background: According to current guidelines, preoperative endoscopic retrograde cholangiopancreatography (ERCP) with biliary stenting (ERCP/stenting) is often necessary in patients with obstructive jaundice due to pancreatic ductal adenocarcinoma (PDAC), including severe jaundice (bilirubin > 250 umol/l), pruritus, cholangitis, cholestatic liver dysfunction, renal failure, severe malnutrition, or delayed surgery for tumors requiring neoadjuvant chemotherapy. We aimed to investigate the impact of preoperative ERCP/stenting on postoperative and long-term outcomes following pancreaticoduodenectomy (PD) for PDAC. Methods: Clinicopathological data of patients who underwent partial/total PD for PDAC between 2012 and 2019 in two hepato-pancreato-biliary centers in Germany and Switzerland were assessed. We compared patients treated with preoperative ERCP/stenting with those directly undergoing surgery according to postoperative morbidity, postoperative mortality, overall survival (OS) and disease-free survival (DFS). Results: During the study period, 192 patients underwent partial/total PD for PDAC. ERCP/stenting was performed in 105 patients, and 87 patients underwent resection without prior intervention. Postoperative 90-day overall morbidity rate (71% vs. 56%, p = 0.029) and superficial surgical site infection (SSI) rate (39% vs. 17%, p < 0.001) were significantly worse following preoperative ERCP/stenting. Major postoperative morbidity rate (18% vs. 21%, p = 0.650), organ/space SSI rate (7% vs. 14%, p = 0.100), and 90-day postoperative mortality rate (4% vs. 2%, p = 0.549) did not significantly differ between the two groups. After excluding 44 patients for whom the indication for ERCP/stenting was not consistent with current guidelines, ERCP/stenting was associated with a higher superficial SSI rate (36% vs. 17%, p = 0.009) and shorter length of stay (12 vs. 16 days, p = 0.004). Median OS (ERCP/stenting: 18 months vs. no ERCP/stenting: 23 months, p = 0.490) and median DFS (ERCP/stenting: 14 months vs. no ERCP/stenting: 18 months, p = 0.645) were independent from the utilization of ERCP/stenting. Conclusions: Preoperative ERCP/stenting in patients with PDAC can be performed without increasing organ/space SSI, major perioperative morbidity, and mortality rates and without worsening oncologic outcomes. However, it is associated with higher superficial SSI rates. If ERCP/stenting is not performed routinely but according to current guidelines, it is also associated with a shorter length of hospital stay. Further refinement of the indications for preoperative ERCP/stenting may reduce superficial SSI rates. Full article

This study aimed to understand the dynamic changes in fibrosis and its relationship with the evaluation of post-treatment viral hepatitis using qFibrosis. A total of 158 paired pre- and post-treatment liver samples from patients with chronic hepatitis B (CHB; n = 100) and C (CHC; n = 58) were examined. qFibrosis was employed with artificial intelligence (AI) to analyze the fibrosis dynamics in the portal tract (PT), periportal (PP), midzonal, pericentral, and central vein (CV) regions. All patients with CHB achieved a virological response after 78 weeks of treatment, whereas patients with CHC achieved a sustained viral response after 24 weeks. For patients initially staged as F5/6 (Ishak system) at baseline, the post-treatment cases exhibited a significant reduction in the collagen proportionate area (CPA) (25–69%) and number of collagen strings (#string) (9–72%) across all regions. In contrast, those initially staged as F3/4 at baseline showed a similar CPA and #string trend at 24 weeks. For regression patients, 27 parameters (25 in the CV region) in patients staged as F3/4 and 15 parameters (three in the PT and 12 in the PP regions) in those staged as F5/6 showed significant differences between the CHB and CHC groups at baseline. Following successful antiviral treatment, the pre- and post-treatment liver samples provided quantitative evidence of the heterogeneity of fibrotic features. qFibrosis has the potential to provide new insights into the characteristics of fibrosis regression in both patients with CHB and CHC as early as 24 weeks after antiviral therapy. Full article

Median arcuate ligament syndrome (MALS) is an uncommon condition characterized by the compression of the celiac trunk by the median arcuate ligament. Due to the anatomical proximity to the foregut, MALS has significant implications in hepato-pancreato-biliary (HPB) surgery. It can pose complications in pancreatoduodenectomy and orthotopic liver transplantation, where the collateral arterial supply from the superior mesenteric artery is often disrupted. The estimated prevalence of MALS in HPB surgery is approximately 10%. Overall, there is consensus for a cautious approach to MALS when embarking on complex foregut surgery, with a low threshold for intraoperative median arcuate ligament release or hepatic artery reconstruction. The role of endovascular intervention in the management of MALS prior to HPB surgery continues to evolve, but more evidence is required to establish its efficacy. Recognizing the existing literature gap concerning optimal management in this population, we describe our tertiary center experience as a clinical algorithm to facilitate decision-making. Research question: What is the significance and management of median arcuate ligament syndrome in patients undergoing hepato-pancreato-biliary surgery? Full article

Gastrointestinal (GI) cancers constitute over 25% of global cancer cases annually, with hepato-pancreato-biliary (HPB) cancers presenting particularly poor prognosis and challenging surgical treatments. While advancements in clinical care have improved post-operative outcomes over time, surgery for HPB cancers remains associated with high morbidity and mortality rates. Patients with HPB cancer are often older, diagnosed at later stages, and have a higher prevalence of co-morbid conditions, leading to reduced life expectancy, suboptimal post-operative recovery, and increased recurrence risk. Exercise and nutrition interventions have emerged as safe non-pharmacological strategies to enhance clinical outcomes among cancer survivors, but their potential in the pre-operative period for patients with HPB cancer remains underexplored. This narrative review evaluates existing evidence on exercise and nutritional interventions during pre-operative prehabilitation for HPB cancer populations, focusing on clinically relevant post-operative outcomes related to frailty and malnutrition. We conducted a literature search in PubMed and Google Scholar databases to identify studies utilizing a prehabilitation intervention in HPB cancer populations with exercise and nutritional components. The currently available evidence suggests that incorporating exercise and nutrition into prehabilitation programs offers a critical opportunity to enhance post-operative outcomes, mitigate the risk of comorbidities, and support overall survivorship among HPB cancer populations. This review underscores the need for further research to optimize the timing, duration, and components of pre-operative prehabilitation programs, emphasizing patient-centered, multidisciplinary approaches in this evolving field. Full article

Hepatocellular carcinoma (HCC) is a tumor that poses a serious threat to human health, with an extremely low five-year survival rate due to its difficulty in early diagnosis and insensitivity to radiotherapy and chemotherapy. To improve the therapeutic efficiency of HCC, we developed a novel multifunctional nanoplatform (SCF NPs) with an amphiphilic polymer (Ce6-PEG2000-FA) and a multitarget tyrosine kinase inhibitor sunitinib. SCF NPs showed superior therapeutical efficiency for HCC due to the synergetic effect of molecular targeted therapy and phototherapy. The Ce6-PEG2000-FA not only serves as a nanocarrier with excellent biocompatibility but also can act as a therapeutic reagent for photothermal therapy (PTT) and photodynamic therapy (PDT). Furthermore, the folic acid group of Ce6-PEG2000-FA enhanced the active targeting performance of SCF NPs. As a multitargeted tyrosine kinase inhibitor, sunitinib in SCF NPs can play a role in molecular targeted therapies, including tumor growth inhibition and anti-angiogenesis. In vivo experiments, SCF NPs showed multimode imaging capabilities, which can be used for tumorous diagnosis and intraoperative navigation. Meanwhile, SCF NPs showed outstanding synergetic tumor inhibition ability. Tumors of SCF NPs group with laser radiation were eradicated without any recrudescence after 14 days of treatment. Such theranostic nanoparticles offer a novel therapeutic tactic for HCC. Full article

(1) Background: Pancreatic cancer is increasingly becoming the leading cause of cancer deaths worldwide. In eukaryotic cells, m6A is the most abundant mRNA methylation modification. (2) Methods: We performed a bioinformatic multidimensional analysis using files containing the clinical data of patients and m6A-related gene expression differences downloaded from web-based databases, and performed a statistical analysis and image mapping mainly using R-package. Next, we studied the RBM15 expression in cancer and paracancerous tissues. We then validated these findings in two cell lines by western blot, PCR, Transwell, CCK-8, and EDU animal models. (3) Results: We discovered that RBM15 was highly expressed in pancreatic cancer patients and that it is a significant cause of poor prognosis. Its association with lymphatic T cell family aggregation was established through immune infiltration analysis. A retrospective analysis of data from clinical patient specimens revealed that high expression of RBM15 in patients was closely and positively correlated with preoperative glucose values, gender, and lymphocyte counts. Results from cellular experiments and animal experiments indicated that when the RBM15 gene was silenced, cell proliferation, migration, and metastasis were inhibited. (4) Conclusions: We propose that RBM15 plays a key role in the progression of pancreatic cancer by promoting tumor proliferation, migration and metastasis. Full article

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers. Full article

As life expectancy is increasing, elderly patients are evaluated more frequently for resection of benign or malignant pancreatic lesions. However, the impact of age on postoperative morbidity, mortality, and treatment costs in octogenarian patients (≥80 years) undergoing major pancreatic surgery needs further investigation. The clinicopathological data of patients who underwent pancreatic surgery between January 2015 and March 2019 in a major hepatopancreatobiliary center in Switzerland were assessed. Postoperative outcomes and hospital costs of octogenarians and younger patients were compared in univariate and multivariate regression analysis. During the study period, 346 patients underwent pancreatic resection. Pancreatoduodenectomy, distal pancreatectomy, total pancreatectomy, and other procedures were performed in 54%, 20%, 13%, and 13% of patients, respectively. The major postoperative morbidity rate and postoperative mortality rate were 25% and 3.5%, respectively. A total of 39 patients (11%) were ≥80 years old, and 307 patients were <80 years old. The majority of octogenarians suffered from ductal adenocarcinoma, whereas among younger patients, other indications for a pancreatic resection were predominant (ductal adenocarcinoma 64% vs. 41%, p = 0.006). Age ≥80 was associated with more frequent postoperative medical (pulmonary, cardiovascular) and surgical (high-grade pancreatic fistula, postoperative hemorrhage) complications. Postoperative mortality was significantly higher in octogenarians (15.4% vs. 2%, p < 0.0001). This finding may be explained by the higher rate of type C pancreatic fistula (13% vs. 5%), resulting more frequently in postoperative hemorrhage (18% vs. 5%, p = 0.002) among patients ≥80 years old. In the multivariate logistic regression analysis, patient age ≥80 years predicted postoperative mortality independently of the tumor entity and surgical technique (p = 0.013, OR 6.71, 95% CI [1.5–30.3]). Increased major postoperative morbidity was responsible for lower cost recovery in octogenarians (94% vs. 102%, p = 0.046). In conclusion, patient age ≥80 years is associated with increased postoperative medical and surgical morbidity after major pancreatic surgery leading to lower cost recovery and a lower chance for successful resuscitation in patients requiring revisional surgery for postoperative hemorrhage and/or pancreatic fistula. In octogenarian patients suffering from pancreatic tumors, careful selection, and thorough prehabilitation is crucial to achieve the best postoperative and long-term oncologic outcomes. Full article