Search Results (114)

There is growing evidence that dysregulation of vesicle-mediated intracellular trafficking pathways leads to the development of various diseases, including cancer. Cancer exploits the intracellular trafficking pathways to modulate the protein flow, alter cell surface protein expression, and drive the hallmarks of cancer progression, such as sustained proliferation signaling and evading immune surveillance. As such, there is increasing interest in understanding the proteins that regulate these processes to better understand cancer biology and to identify novel ways to hinder disease progression. A group of small proteins, known as the Tumor Protein D52 (TPD52)-like family, has been identified and is increasingly recognized for its roles in intracellular trafficking within cancer cells. This family consists of four members: TPD52, TPD53, TPD54, and TPD55. Herein, we review the current literature on the TPD52-like family in cancer and detail the current known cellular functions (e.g., intracellular trafficking roles, lipid biogenesis, cell proliferation, and cell cycle regulation). Overexpression of family members, notably TPD52 and TPD54, has been heavily implicated in tumorigenic roles such as cell migration, invasion, proliferation, and protein–protein interactions. Additionally, there is mounting evidence that this family also has isoform-specific and/or tissue-specific functions, which is of clinical interest. A better understanding of the mechanistic actions of this protein family holds the promise of identifying novel therapeutic targets that exploit the broader multi-target nature of intracellular trafficking regulators to disrupt oncogenic processes. Full article

Background: Enterococcus faecium bloodstream infections (EF-BSI) cause significant morbidity and mortality in solid organ transplant (SOT) recipients, with the role of vancomycin resistance (VR) remaining controversial as an independent driver. Methods: This was a retrospective cohort study including SOT recipients with EF-BSI at our institution from 2019 to 2023. We used Cox proportional hazards regression to identify predictors of 30-day all-cause mortality. A time-dependent covariate was used to model the effects of receiving targeted, effective antibiotic therapy. Results: A total of 79 patients were included (26.6%, with VR). The overall 30-day mortality was 12.7% (10/79). In univariable analysis, septic shock (Hazard Ratio, HR: 17.1, 95% CI: 3.64–80.8, p < 0.001), the need for Continuous Venovenous Hemofiltration (HR: 6.40, 95% CI: 1.85–22.1, p = 0.003), and a Pitt Bacteremia Score ≥ 2 (HR: 5.17, 95%CI: 1.10–24.3, p = 0.038) were associated with increased mortality, while source control was protective (HR: 0.20, 95% CI: 0.05–0.76, p = 0.018). In the final multivariable model, only septic shock remained an independent predictor of 30-day mortality (HR: 11.4, 95% CI: 1.63–79.5, p = 0.014). VR was not significantly associated with mortality, though the confidence interval was wide and included clinically meaningful effects (HR: 2.07, 95% CI: 0.40–10.6, p = 0.4). Conclusions: In SOT recipients with EF-BSI, 30-day mortality is overwhelmingly driven by the host’s physiological response, manifested as septic shock, rather than the VR profile of the pathogen. The early recognition of severe sepsis/septic shock and the aggressive implementation of supportive care and source control measures in this setting are crucial. Full article

The gut immune microenvironment and the liver engage in intricate information exchange via the gut–liver axis. The disruption of these interactions plays a pivotal role in the formation and exacerbation of pathological damage to the liver. The gut immune microenvironment is not an independent layer of the gut barrier; rather, it permeates and regulates all other barrier functions, serving as the core coordinator. Disruption of the immune microenvironment in the gut–liver axis drives progression across the full disease spectrum—from steatosis to hepatitis, fibrosis, and even liver cancer—through the continuous influx of immune-stimulatory signals that overwhelm the liver’s intrinsic immune regulatory mechanisms. Dysfunction of innate immunity components, amplification of inflammatory factors and key cellular signaling pathways, activation of adaptive immune T cells, and systemic effects mediated by liver-derived inflammatory factors collectively form a disordered immune microenvironment. This damages the intestinal barrier and exacerbates liver disease via the gut–liver axis, leading to further intestinal injury, thus establishing a self-reinforcing vicious cycle. Current therapeutic strategies based on modulating the gut–liver axis microenvironment remain limited, yet studies have demonstrated that suppressing gut immune cells, cytokines, and signaling pathways can help delay liver disease progression. Hopefully, future combined, precise, and cutting-edge gut immunotherapies will provide more effective strategies for liver disease treatment. Full article

Introduction: Graft and patient survival after kidney transplantation in children has increased in the past decade; however, post-transplant surgical complications occur in up to 15.4% of recipients and pose a significant threat to graft survival. Due to anatomic discrepancies in children, kidney transplantation in this population is nuanced and requires meticulous planning. This narrative review summarizes the most common postoperative surgical complications following kidney transplantation in children. Methods: PubMed and Google Scholar were queried for full-text articles that reported pediatric kidney transplantation surgical complications and their management following kidney transplantation. Results: Vascular complications can occur in approximately 1.3–13.8% of cases and are the leading cause of graft nephrectomy, with arterial stenosis and venous thrombosis being the most common. Urologic complications occur in 1.3–30% of patients and are more frequent in children due to pre-existing genitourinary abnormalities prior to transplantation. Vesicoureteral reflux is the most common urologic complication. Discussion: Surgical complications following kidney transplantation in children continue to significantly affect graft viability. Ultimately, meticulous surgical techniques and close postoperative surveillance are critical to mitigating the risk of allograft nephrectomy. Prospective studies focused on best surgical practice, techniques, prevention, and postoperative care in pediatric kidney transplant recipients are needed. Full article

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

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory roles throughout MASLD progression remain insufficiently defined. A 10-week high-fat, choline-deficient (HFCD) mouse model was established, and liver pathology was evaluated at weeks 6, 8, and 10. Time-resolved assessments combined untargeted metabolomics, magnetic resonance imaging–proton density fat fraction (MRI-PDFF), serum biochemistry, histological staining, immunofluorescence, and transmission electron microscopy to characterize dynamic alterations in lipid metabolism, redox status, inflammation, and fibrogenesis. The HFCD diet produced a clear temporal sequence of liver injury. Steatosis, phosphatidylcholine depletion, and early antioxidant loss appeared by week 6. By week 8, mitochondrial structural damage and pronounced cytokine elevation were evident. At week 10, collagen deposition and α-SMA activation signaled fibrotic progression. Metabolomics indicated significant disruptions in pathways related to ATP-binding cassette (ABC) transporters, one-carbon metabolism, and the tricarboxylic acid (TCA) cycle. Using integrated analytical strategies, this study suggests that choline deficiency may be associated with a time-dependent pathological cascade in MASLD, beginning with phospholipid destabilization and extending to altered mitochondria–endoplasmic reticulum crosstalk at mitochondria-associated membranes, alongside amplified oxidative–inflammatory responses, which collectively may contribute to progressive fibrogenesis as the disease advances. 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

Background: Osteosarcoma (OS) is the most common primary malignant bone tumor, mainly affecting adolescents and young adults. While lung metastases are common, visceral metastases in the hepatopancreatobiliary system are extremely rare and usually associated with a poor prognosis. The limited diagnostic and therapeutic options for such metastases make the treatment of affected patients difficult. The possibility of very late metastatic onset in high-grade OS highlights the potential need for extended follow-up (FU) beyond established intervals. Methods: This study combines a retrospective analysis of prospectively collected data from the Vienna Bone and Soft Tissue Tumor Registry with a review of the literature of patients with OS and metastases to the hepatopancreatobiliary system. A descriptive statistical analysis is presented for the entire cohort. In addition, publications from scientific databases (PubMed, Embase) were analyzed to evaluate the frequency, diagnosis, therapy, and prognosis of visceral metastasis from both conventional OS and primary extraskeletal osteosarcoma (ESOS). Results: A total of six male patients with conventional OS and metastases in the liver (5) and pancreas (1), with a mean lesion size of 38 mm (range, 10–120), were included. The median age at the time of visceral metastasis was 29 years (mean, 32 years; range, 20–62 years), and the mean interval since initial diagnosis was five years and ten months (range, 9 months–10 years and 9 months). Visceral metastases are very rare in general and usually occur in advanced stages of disease. We identified 51 cases of visceral metastases from conventional OS and 34 cases of ESOS in the hepatopancreatobiliary system in the literature. The metastasis interval was three years (range, 15 months before diagnosis–17 years) at a median age of 27 years (mean, 32 years; range, 10–69 years). Conclusions: Visceral metastases from OS are rare but represent a significant therapeutic challenge. Early, targeted imaging in combination with improved methods for diagnosis confirmation and interdisciplinary treatment strategies may potentially improve the results. This study underlines the importance of early diagnosis and highlights the need for individualized long-term surveillance strategies exceeding ten years, especially in high-grade OS, aiming at early detection of late-onset metastasis. Full article

Background: The management of complex hepato-pancreato-biliary (HPB) pathologies demands exceptional surgical precision. Traditional two-dimensional imaging has limitations in depicting intricate anatomical relationships, potentially complicating preoperative planning. This review explores the synergistic application of three-dimensional (3D) reconstruction and artificial intelligence (AI) to support surgical decision-making in complex HPB cases. Methods: This narrative review synthesized the existing literature on the applications, benefits, limitations, and implementation challenges of 3D reconstruction and AI technologies in HPB surgery. Results: The literature suggests that 3D reconstruction provides patient-specific, interactive models that significantly improve surgeons’ understanding of tumor resectability and vascular anatomy, contributing to reduced operative time and blood loss. Building upon this, AI algorithms can automate image segmentation for 3D modeling, enhance diagnostic accuracy, and offer predictive analytics for postoperative complications, such as liver failure. By analyzing large datasets, AI can identify subtle risk factors to guide clinical decision-making. Conclusions: The convergence of 3D visualization and AI-driven analytics is contributing to an emerging paradigm shift in HPB surgery. This combination may foster a more personalized, precise, and data-informed surgical approach, particularly in anatomically complex or high-risk cases. However, current evidence is heterogeneous and largely observational, underscoring the need for prospective multicenter validation before routine implementation. 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

Frozen section (FS) analysis is a rapid intraoperative tool that provides real-time pathological assessment, guiding surgical decisions in gastrointestinal and hepatobiliary disease. Its main applications include confirming diagnoses, assessing resection margins, staging lymph nodes, and evaluating unexpected intraoperative findings. Drawing on a 14-year experience at Queen’s Medical Centre, Nottingham, this review highlights the strengths and limitations of FS in gastrointestinal and hepatopancreato-biliary surgery. Concordance with final paraffin diagnoses exceeded 97%, underscoring its reliability when performed under optimal conditions. FS is particularly valuable in complex scenarios such as distinguishing benign from malignant hepatic or pancreatic lesions, identifying metastatic disease, and evaluating conditions like Hirschsprung disease. Although interpretive artefacts and sampling errors remain challenges, careful technique and close clinical–pathological communication mitigate these issues. Beyond diagnosis, FS also supports molecular applications through targeted tissue selection for genomic testing. Overall, FS remains an essential adjunct to modern surgical pathology, enhancing intraoperative decision-making and contributing to precision oncology. Looking ahead, the integration of FS with artificial intelligence, telepathology, and minimally invasive surgical platforms is poised to expand its accuracy, accessibility, and impact in real-time precision surgery. Full article

Background and Objectives: Bile leak is a common complication after hepatopancreatobiliary surgery, requiring timely management to prevent life-threatening outcomes. Endoscopic retrograde cholangiopancreatography (ERCP) is essential in treatment, but large data concerning optimal timing and technique selection are unavailable. This study evaluates whether the timing of ERCP influences healing and if different bile duct injuries affect outcomes. Materials and Methods: Data from a prospectively maintained database over 25 years (2001–2025) included 176 patients (M/F: 91/85, mean age 62) undergoing ERCP for bile leaks. Results: Most leaks followed cholecystectomy (n = 143, 81.5%). The median time from leak to ERCP was 7 days. Ten patients (5.7%) had complete common bile duct (CBD) transection—considered major leaks—requiring surgery. Among the 166 minor leaks, the cystic duct stump (40.1%) was the most common injury site, followed by the CBD (24.1%) and the gallbladder bed (15.4%). Healing occurred in 90.6%. Stent placement improved healing rates (93.9% vs. 75.9%, p = 0.007), with no difference between pig-tail and (Amsterdam) straight plastic stents (90% vs. 96%, p = 0.267). Retained CBD stones or CBD strictures did not affect outcomes. Leaks from the cystic duct stump had a 96.9% resolution rate, whereas gallbladder bed leaks healed in 88%. The median healing time was 2 days, unaffected by stent placement or ES alone (p = 0.842), but later ERCP correlated with longer healing (RR: 0.362, p < 0.001). Following a right aberrant bile leak, the time for healing was longer than in leaks from other sites. Conclusions: ERCP with stenting remains the first-line approach for minor bile leaks. Early ERCP accelerates healing, emphasizing the importance of prompt intervention. 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/Objectives: Cholecystectomy (CE) is among the most commonly performed surgical procedures worldwide. While it effectively treats gallstone disease, concerns have been raised about a potential long-term association with colorectal cancer (CRC), given overlapping risk factors and post-surgical physiological changes. Previous studies have reported inconsistent findings. This updated systematic review aimed to reassess the association between CE and CRC risk by incorporating the most recent evidence. Methods: In accordance with PRISMA 2020 guidelines, a systematic literature search was conducted in PubMed, Embase, Medline, Web of Science, and the Cochrane Library for studies published after May 2022. Eligible studies were observational cohort studies reporting relative risk estimates for CRC following CE. Data were extracted manually, and study quality was assessed using the NewcastleOttawa Scale (NOS). Only high-quality studies were included to update the systematic review. Publication bias was assessed using funnel plots and Egger’s test. Results: Out of 156 identified records, three new high-quality cohort studies met the inclusion criteria and were added to the 18 studies from the previous review, resulting in a total of 21 studies. The findings were heterogeneous: while no consistent association with overall CRC risk was observed, several studies reported an elevated risk of proximal (right-sided) colon cancer following CE. Egger’s test indicated no significant publication bias (p = 0.50). Conclusions: This updated systematic review suggests a potential association between CE and an increased risk of proximal colon cancer; however, the evidence remains inconclusive. Further prospective studies with robust confounder control and detailed tumor location-specific analyses are warranted to clarify causality and guide future screening strategies. Full article