Search Results (116)

Background: Pancreatic cancer (PC) has a very poor 5-year survival and prognosis. Even when CT or MRI shows no metastasis, staging laparoscopy(SL) still detects tiny peritoneal deposits in 20–30% of patients, making them ineligible for surgery. SL is invasive, requiring general anesthesia and substantial resources. Endoscopic ultrasound (EUS) allows the observation of the bile ducts, pancreas, and abdominal cavity, and EUS-guided fine-needle aspiration (EUS-FNA) is essential for pathological diagnosis. Reports on using EUS to perform peritoneal lavage cytology are currently not available. We hypothesized that combining EUS-FNA with peritoneal lavage (EUS-lavage technique; EUS-LT) could enhance staging accuracy and avoid unnecessary surgical procedures. Methods: Ten ex vivo porcine models underwent EUS-LT. Using a 19G FNA needle, 800 mL saline was instilled into the intraperitoneal cavity and then recovered. Two refinements were introduced sequentially: an ENBD catheter with additional side holes and, subsequently, a side-hole introducer (EndoSheather) that eliminated balloon dilation. The primary endpoint was procedural success. Secondary endpoints included safety, complications, recovered volume, duration of endoscopic procedure, and time required to instill 800 mL. Nonparametric tests compared outcomes across iterations. Results: Ten-model porcine ex vivo model series were included, and all procedures were successful. No device malfunctions or unanticipated technical failures; one minor mucosal injury during saline injection resolved after re-puncture. The average procedure time was 31.1 min. Stepwise refinements shortened procedure and infusion times and increased recovered volume. Recovered volume approached the instilled amount in later cases, indicating efficient performance. Conclusions: In this ten-model ex vivo series, EUS-LT demonstrated technical feasibility and short-term safety. Full article

Background: Traumatic injuries of the duodenum are generally rare but when they occur, they can result in serious complications. Inaccurate injury classification, delayed diagnosis, or late treatment can significantly raise morbidity and mortality. A multidisciplinary approach is often necessary. Mechanisms of injury: Isolated duodenal injuries are relatively uncommon due to the duodenum’s proximity to pancreas and major vascular structures. Duodenal injuries can result from blunt or penetrating trauma. Classification: The 2019 World Society of Emergency Surgery (WSES)-American Association for the Surgery of Trauma (AAST) guidelines recommend incorporating both the AAST-OIS grading and the patient’s hemodynamic status to stratify duodenal injuries into four categories: Minor injuries WSES class I, Moderate injuries WSES class II, Severe injuries WSES class III, and WSES class IV. Diagnosis: The diagnostic approach involves a combination of clinical assessment, laboratory investigations, radiological imaging and, in particular situations, surgery. Prompt diagnosis is critical because delays exceeding 24 h are associated with a higher incidence of postoperative complications and a significant rise in mortality. Contrast-enhanced abdominal computed tomography (CT) represents the gold standard for diagnosis in patients who are hemodynamically stable. Management: Duodenal trauma requires a multimodal approach that considers hemodynamic stability, the severity of the injury and the presence of associated lesions. Non-operative management (NOM) is reserved for hemodynamically stable patients with minor duodenal injuries without perforation (AAST I/WSES I), as well as all duodenal hematomas (WSES I–II/AAST I–II) in the absence of associated abdominal organ injuries requiring surgical intervention. All hemodynamically unstable patients, those with peritonitis, or with CT findings consistent with duodenal perforations or AAST grade III or higher injuries are candidates for emergency surgery. If intervention is required, primary repair should be the preferred option whenever feasible, while damage control surgery is the best choice in cases of hemodynamic instability, severe associated injuries, or complex duodenal lesions. Definitive reconstructive surgery should be postponed until the patient has been adequately resuscitated. The role of endoscopic techniques in the treatment of duodenal injuries and their complications is expanding. Conclusions: Duodenal trauma is burdened by potentially high mortality. Among the possible complications, duodenal fistula is the most common, followed by duodenal obstruction, bile duct fistula, abscess, and pancreatitis. The overall mortality rate for duodenal trauma persists to be significant with an average rate of 17%. Future prospective research needed to reduce the risk of complications following duodenal trauma. Full article

Background/Objectives: Biliary complications are common after liver transplantation (LT), with bile leaks representing a major cause of morbidity. Conventional imaging modalities such as ultrasound, CT, MRCP, and endoscopic techniques may fail to localize peripheral or complex leaks. This study aimed to evaluate the feasibility of [⁶⁸Ga]Ga-TEoS-DAZA-PET/CT for non-invasive localization of bile leaks after LT. Methods: Five male patients (mean age 53.2 years) with suspected bile leakage and inconclusive prior imaging underwent [⁶⁸Ga]Ga-TEoS-DAZA-PET/CT. The tracer was synthesized under GMP conditions and administered at a mean activity of 204 ± 42 MBq. Dynamic PET/CT imaging was performed for 60 min, and findings were classified according to the Nagano classification. Results: Bile leaks were detected and anatomically localized in all five patients. Sites included the liver resection surface, central bile ducts, bilioenteric anastomosis, and biliary drainage exit. PET/CT findings guided revision surgery in one case and endoscopic treatment in three, while one patient improved without intervention. No adverse effects occurred. Conclusions: [⁶⁸Ga]Ga-TEoS-DAZA-PET/CT is a feasible and safe imaging technique for the anatomical localization of bile leaks following LT. Its antegrade visualization of biliary flow, high spatial and temporal resolution, and lack of contraindications make it a promising complementary modality when conventional imaging is inconclusive or not feasible. Larger studies are warranted to validate its diagnostic value and clinical utility in postoperative and post-traumatic biliary injuries. Full article

Cholangiopathies encompass a wide range of chronic liver diseases that target biliary epithelial cells, leading to significant morbidity and mortality due to their progressive nature, limited treatment options, and complex clinical management. Currently, clinically validated biomarkers capable of distinguishing obstructive cholangiopathies, such as biliary atresia (BA), from other cholangiopathies are lacking, hindering timely intervention. RNA-binding proteins (RBPs) have been increasingly linked to human diseases but their roles in cholangiopathies remain underexplored. We assessed the expression of the RBP epithelial splicing regulatory protein 1 (ESRP1) in murine models of cholangiopathies and in the human system. Our findings demonstrate that ESRP1 is highly and specifically expressed in cholestatic liver injury models, including bile duct-ligated, diethoxycarboncyl-1,4-dihydrocollidine-treated, and Mdr2^−/− mice when compared with other liver injury models. Importantly, ESRP1 is markedly elevated in the livers of patients with BA and cystic fibrosis-related liver disease, localizing to cholangiocytes and peri-biliary hepatic cells, but is minimal in primary sclerosing cholangitis and primary biliary cholangitis. Moreover, patient-derived BA organoids and biliatresone-treated healthy organoids also display ESRP1 expression. Bioinformatics analysis further implicates ESRP1 in key cholangiopathy-associated pathways, warranting deeper mechanistic investigation. Thus, ESRP1 holds potential as a molecular marker for obstructive cholangiopathies, warranting further mechanistic studies. 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

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies, but they may cause a wide range of immune-related adverse events (irAEs). Hepatic toxicity occurs in approximately 1–6% of patients treated with nivolumab and usually presents with a hepatocellular pattern responsive to corticosteroids. The cholestatic-predominant immune-mediated hepatitis seems to respond poorly to immunosuppression. We describe an 87-year-old man with metastatic melanoma treated with nivolumab who developed steroid-refractory, cholestatic-predominant immune-mediated hepatitis after 18 cycles of therapy. Laboratory tests revealed a mixed but predominantly cholestatic pattern (ALT 585 U/L, GGT 2261 U/L, total bilirubin 2.0 mg/dL). Imaging excluded biliary obstruction or hepatic metastases. Liver biopsy showed acute lobular hepatitis with intracanalicular cholestasis and mild bile duct injury, consistent with immune-mediated, drug-induced injury (Ishak score 5). Mycophenolate mofetil produced only partial biochemical improvement. The patient died one month later from influenza A pneumonia in the context of combined immunosuppressive therapy. This case illustrates a cholestatic-predominant phenotype of nivolumab-induced hepatitis, characterized by poor corticosteroid response and incomplete recovery despite second-line immunosuppression. Recognition of this entity is essential, as early introduction of agents such as mycophenolate may improve outcomes. In elderly and frail patients, however, the risks of intensified immunosuppression must be carefully balanced against infection risk, highlighting the need for individualized management and vigilant monitoring. 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

Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive bile duct inflammation and fibrosis. Its strong association with inflammatory bowel disease (IBD) highlights the possible role of the gut–liver axis in disease pathogenesis. Here, we review the mechanisms that may contribute to the disruption of the gut–liver axis, leading to liver injury and the development of PSC. In particular, disruption of the intestinal barrier allows microbial products to enter the portal circulation, stimulating hepatic immune cells and triggering biliary inflammation. Concurrently, gut-primed lymphocytes expressing mucosal homing receptors migrate aberrantly to the liver, where they may contribute to biliary epithelial cell injury. Dysbiosis, characterized by reduced microbial diversity and the expansion of bile-tolerant and pro-inflammatory taxa, amplifies this immune activation and disturbs gut–liver homeostasis. Moreover, bile acids act as signaling molecules, regulating metabolism and immune responses through receptors such as FXR and TGR5. Dysregulation of these pathways may promote cholestasis, inflammation, and fibrosis. By understanding these interactions, we may identify novel therapeutic targets for PSC. Full article

Background: Laparoscopic subtotal cholecystectomy (LSTC), either fenestrating or reconstituting, offers potential benefits for the “difficult gallbladders” in terms of reduced bile duct injury (BDI) risk. Methods: This single-center retrospective cohort study analyzed data from patients who underwent reconstituting or fenestrating LSTC at a tertiary care center. We excluded patients who were converted to open cholecystectomy or had incomplete medical records. The data examined included demographic and clinical characteristics, preoperative assessments, operative details, and postoperative outcomes. No multivariable regression was performed because of the limited sample size. Results: The study included 46 patients (reconstituting: 20 patients; fenestrating: 26 patients). The severity of cholecystitis assessed by the Tokyo guidelines showed a higher proportion of Grade 2 severity in the reconstituting group than the fenestrating group (90% vs. 56.5%; p = 0.027). Both surgical techniques were similarly challenging and showed no significant differences in operative difficulty, operative duration, blood loss, or total hospital stay. Fenestrating procedures had non-significantly higher incidences of BDI (7.7% vs. 0%; p = 0.21), bile leakage (23.1% vs. 10%; p = 0.246), and intraoperative drain placement (88.5% vs. 75%; p = 0.232). Postoperative complications such as bile leaks were also comparable between the two techniques. Nevertheless, given the small sample, these observations are descriptive and should not be interpreted as evidence of comparability or superiority. Conclusions: Despite limitations, our analysis suggests that fenestrating and reconstituting approaches have comparable postoperative outcomes, although fenestrating procedures were associated with slight but non-significant increases in BDI and drain placement due to leaks. The choice of LSTC technique should depend on intraoperative findings, surgical expertise, and familiarity with each technique, but further studies are needed to obtain firm conclusions. Full article

This study investigated the structural features of adult duck liver and compared pathological alterations induced by duck Tembusu virus (DTMUV, strain XZ-2012) and lipopolysaccharide (LPS). Histological techniques (HE, reticular fiber, and trichrome staining) revealed normal duck liver exhibited reddish-brown coloration with indistinct lobule boundaries and no prominent bile ducts. Kupffer cell distribution was mapped via jugular ink injection. DTMUV infection caused liver swelling, congestion, and yellowish discoloration. Histopathology showed lymphocyte infiltration around central veins and portal areas, increased reticular fibers, thickened basement membranes, hepatocyte vacuolation, and erythrocyte accumulation in sinusoids. In contrast, LPS exposure led to mild hepatic enlargement without vacuolar degeneration but with marked perivascular lymphocyte aggregation and reticular fiber proliferation. Both treatments elevated Kupffer cell numbers. These findings demonstrate distinct liver injury patterns: DTMUV induces direct hepatocellular damage with inflammatory responses, while LPS triggers intense immune cell recruitment without significant hepatocyte degeneration. The study provides insights into avian viral versus bacterial pathogenesis and liver defense mechanisms, offering a foundation for further research into waterfowl infectious diseases. Full article

Background: Common bile duct (CBD) treatments are often associated with complications, limiting long-term efficacy. To overcome these issues, polymeric grafts have been suggested as promising alternatives, since they are highly customizable, biocompatible, and may reduce side effects frequency. Methods: A systematic review was conducted, interrogating MEDLINE and Cochrane Library. Next, an in vivo study involved 20 pigs, which underwent a former controlled biliary injury. To repair the defect, a α,β-Poly(N-2-hydroxyethyl)-DL-Aspartamide (PHEA)–Polylactic-acid (PLA)–Polycaprolactone (PCL) scaffold was implanted. The animals were sacrificed at one and three months for gross and histological examinations, to assess tissue integration and healing outcomes. Results: The systematic review highlighted that such scaffolds have shown promising results in CBD regeneration, both in single and joined applications. These findings were confirmed by the in vivo study, where the use of such scaffolds—particularly, the planar ones—led to safe and complete bile duct regeneration. Histological analysis revealed lymphomonocytic infiltrates and neovascularization, while microscopic examination showed progressive scaffold degradation accompanied by biliary tissue regeneration. Conclusions: Experimental results are consistent with the literature, confirming the potential of such polymeric scaffolds in aiding complete CBD regeneration and being reabsorbed shortly after. Still, further studies are needed to fully validate their translational application. PROSPERO ID: CRD420251115056. Full article

Primary biliary cholangitis (PBC) is a chronic, immune-mediated liver disease characterized by progressive destruction of the small intrahepatic bile ducts, leading to cholestasis, inflammation, and ultimately fibrosis and cirrhosis. This review emphasizes the central role of bile acids in PBC pathogenesis, exploring how disruptions in their synthesis, transport, and detoxification contribute to cholangiocyte damage and disease progression. In addition to discussing the autoimmune features of PBC, including the presence of specific autoantibodies and cellular immune responses, we examine how bile acid dysregulation exacerbates cholestasis and promotes lipid metabolic disturbances. Particular attention is given to the “bicarbonate umbrella” hypothesis, which describes a protective mechanism by which cholangiocytes resist bile acid–induced injury—an essential factor disrupted in PBC. The aim of this review is to summarize current knowledge gaps in the pathophysiology of PBC, with a focus on the role of bile acids not only as key drivers of disease mechanisms, but also as potential biomarkers of disease progression and treatment response. Full article

Urolithin (Uro)-B, a gut microbiota metabolite of ellagic acid, has recently gained considerable attention due to its beneficial bioactivities. This study investigated the potential hepatoprotective effect of Uro-B against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and explored the possible involved mechanisms. Mice were treated with Uro-B (50 and 100 mg/kg) for four days and received ANIT (75 mg/kg) once on the second day. Our data revealed that Uro-B reduced elevated serum transaminases, alkaline phosphatase, lactate dehydrogenase, and total bilirubin levels associated with ANIT injection. Histopathologically, Uro-B effectively ameliorated ANIT-induced disruption of the hepatic architecture as represented by repressed necro-inflammation and bile duct proliferation. Uro-B also maintained oxidant/antioxidant status that was dysregulated by ANIT. Mechanistically, Uro-B markedly activated Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling with subsequent upregulation of hepatic heme oxygenase-1 expression. On the other hand, Uro-B suppressed the ANIT-induced expression of nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Interestingly, Uro-B repressed peroxisome proliferator-activated receptor alpha (PPARα) expression in the liver. These findings indicate a promising hepatoprotective effect of Uro-B against ANIT-induced CLI in mice. Uro-B modulated the interplay between Keap1/Nrf2, NF-κB/TNF-α, and PPARα signaling pathways, resulting in powerful antioxidant and anti-inflammatory effects. Full article

Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article

This case report describes index pancreatoduodenectomy in a 32-year-old male following a close-range gunshot wound to the abdomen, with consequent 4 cm pancreatic head defect, duodenal and common bile duct perforation, right kidney laceration, and through-and-through inferior vena cava (IVC) injury. Although standard trauma protocols often favor damage control surgery (DCS) with delayed reconstruction in unstable patients, this patient’s hemodynamic stability—attributed to retroperitoneal self-tamponade—enabled a single-stage definitive approach. The rationale for immediate reconstruction was to prevent the risks associated with delayed management, such as ongoing pancreatic and biliary leakage, chemical peritonitis, and subsequent sepsis or hemorrhage. This case highlights that, in select stable patients with severe pancreaticoduodenal trauma, immediate pancreatoduodenectomy may be preferable to DCS, provided care is delivered in a high-volume hepatopancreaticobiliary (HPB) center with appropriate expertise and resources. Full article