Changes in beta-catenin expression and activation during progression of primary sclerosing cholangitis predict disease recurrence

Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. We have previously demonstrated the importance of Wnt/β-catenin signaling in mouse models of PSC. In this study, we wished to determine the clinical relevance of β-catenin localization in patient samples. In livers explanted from patients diagnosed with PSC, the majority (12/16; 75%) lacked β-catenin protein expression. Biopsies from patients post-transplant were classified as recurrent or non-recurrent based on pathology reports and then scored for β-catenin activation as a function of immunohistochemical localization. Despite lack of statistical significance, patients with recurrent primary disease (n = 11) had a greater percentage of samples with nuclear, transcriptionally active β-catenin (average 58.8%) than those with no recurrence (n = 10; 40.53%), while non-recurrence is correlated with β-catenin staining at the cell surface (average 52.63% for non-recurrent vs. 27.34% for recurrent), as determined by three different methods of analysis. β-catenin score and years-to-endpoint are both strongly associated with recurrence status (p = 0.017 and p = 0.00063, respectively). Finally, there was significant association between higher β-catenin score and increased alkaline phosphatase, a marker of biliary injury and disease progression. Thus, β-catenin expression and activation changes during the progression of PSC, and its localization may be a useful prognostic tool for predicting recurrence of this disease.

Diagnosis of a single gallbladder with double cystic ducts and dominant accessory duct draining into the right hepatic duct: a case report

Biliary anomalies are a high risk for biliary injury during surgery, and although a biliary anomaly is occasionally encountered, variations in cystic ducts are rare. A preoperative diagnosis is highly valuable in facilitating surgical procedures and avoiding surgical complications. Herein, the case of a 67-year-old female patient with acute cholecystitis, in which preoperative fluoroscopic cholangiography clearly demonstrated a single gallbladder with double cystic ducts, is presented. The accessory duct was found to be dominant, draining into the otherwise normal right intrahepatic bile duct, and laparoscopic cholecystectomy was performed smoothly and successfully. Fluoroscopic cholangiography is a powerful tool that may clearly depict the anomaly of a single gallbladder with double cystic ducts. Through appropriate preoperative knowledge and demonstration of this biliary anomaly in the present case, laparoscopic cholecystectomy was safely performed, and the patient was symptom-free at the 3-year follow-up assessment.

Thrombolytic Therapy During ex-vivo Normothermic Machine Perfusion of Human Livers Reduces Peribiliary Vascular Plexus Injury

Background: A major limitation in expanding the use of donation after circulatory death (DCD) livers in transplantation is the increased risk of graft failure secondary to ischemic cholangiopathy. Warm ischemia causes thrombosis and injury to the peribiliary vascular plexus (PVP), which is supplied by branches of the hepatic artery, causing higher rates of biliary complications in DCD allografts.Aims/Objectives: We aimed to recondition discarded DCD livers with tissue plasminogen activator (tPA) while on normothermic machine perfusion (NMP) to improve PVP blood flow and reduce biliary injury.Methods: Five discarded DCD human livers underwent 12 h of NMP. Plasminogen was circulated in the base perfusate prior to initiation of perfusion and 1 mg/kg of tPA was administered through the hepatic artery at T = 0.5 h. Two livers were split prior to perfusion (S1, S2), with tPA administered in one lobe, while the other served as a control. The remaining three whole livers (W1-W3) were compared to seven DCD control liver perfusions (C1-C7) with similar hepatocellular and biliary viability criteria. D-dimer levels were measured at T = 1 h to verify efficacy of tPA. Lactate, total bile production, bile pH, and difference in biliary injury scores before and after perfusion were compared between tPA and non-tPA groups using unpaired, Mann-Whitney tests.Results: Average weight-adjusted D-dimer levels were higher in tPA livers in the split and whole-liver model, verifying drug function. There were no differences in perfusion hepatic artery resistance, portal vein resistance, and arterial lactate between tPA livers and non-tPA livers in both the split and whole-liver model. However, when comparing biliary injury between hepatocellular and biliary non-viable whole livers, tPA livers had significantly lower PVP injury scores (0.67 vs. 2.0) and mural stroma (MS) injury scores (1.3 vs. 2.7).Conclusion: This study demonstrates that administration of tPA into DCD livers during NMP can reduce PVP and MS injury. Further studies are necessary to assess the effect of tPA administration on long term biliary complications.

Laparoscopic-Assisted Transgastric Endoscopic Retrograde Cholangiopancreatography With Placement of a Biliary Stent to Treat Traumatic Intrahepatic Bile Duct Disruption in a Patient With Roux-en-Y Gastric Bypass

Hepatic injuries are common following blunt trauma and while frequently managed expectantly, biliary injury as a result of the trauma requires a high index of suspicion, a focused workup, and likely interventional treatment. A 44-year-old female with a history of Roux-en-Y gastric bypass presented after a ground level fall and was initially discharged home but represented with worsening abdominal pain and elevated liver enzymes. She was found to have a segment 5/6 biliary injury requiring laparoscopic-assisted transgastric endoscopic retrograde cholangiopancreatography with common bile duct stent placement. This case represents the difficulty of diagnosing biliary injuries following blunt trauma, and the need for advanced endoscopic interventions for treatment in patients with atypical anatomy.

The Role of Endoscopic Retrograde Cholangiopancreatography in the Management of Biliary Complication Post-Laparoscopic Cholecystectomy

BACKGROUND: Laparoscopic cholecystectomy considers a golden surgery for gallbladder removal nowadays, and it carries some complications like biliary injuries, which can manage successfully by endoscopic retrograde cholangiopancreatography. AIM: To estimate the role of endoscopic management of bile duct injury (BDI) following laparoscopic cholecystectomy. PATIENT AND METHODS: A prospective study conducted at Al-Sader Medical City, Najaf City, Iraq, during the period between September 2018 and December 2020, included 44 patients complicated by the biliary injury resulting in a persistent biliary leak and/or jaundice after laparoscopic cholecystectomy and evaluated by endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Findings revealed that 25% of cases had complete BDI, only one managed by plastic stent placement, the other 10 referred for open surgical constructions, 61% had partial injury associated with the biliary leak, all managed by sphincterotomy and plastic stent placement through ERCP, almost 7% had a partial clipping of bile duct all managed with sphincterotomy, balloon dilatation/stone extraction, and plastic stent placement, 5% had slipped clips of cystic duct stump, are managed with sphincterotomy and plastic stent placement. Moreover, only one patient, 2%, had distal common bile duct stone with bile leak, managed by sphincterotomy and stone extraction. CONCLUSIONS: Laparoscopic cholecystectomy, a gold standard therapeutic option for symptomatic cholecystolithiasis, is associated with an increased risk of biliary injury due to many factors. ERCP is a safe means of diagnosing the cause of bile leakage after laparoscopic cholecystectomy. It also offers definitive treatment in most cases by endoscopic sphincterotomy and plastic stent placement.