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To compare the effect of endoscopic balloon dilation (EPBD) of the papilla with that of endoscopic biliary sphincterotomy (EST) in the treatment of patients with common bile duct stones. Searches of computerized bibliographic and scientific citations, and review of citations in relevant primary articles. Eight fully published prospective, randomized trials in English that compared EPBD with EST for the removal of common bile duct stones were subjected to metaanalysis. EPBD compared with EST resulted in similar outcomes with regards to overall successful stone removal (94.3% vs 96.5%) and overall complications (10.5% vs 10.3%). Bleeding occurred less frequently with EPBD (0% vs 2.0%, p = 0.001). Post-ERCP pancreatitis occurred more commonly in the EPBD group (7.4% vs 4.3%, p = 0.05). No significant differences were seen in the rates of perforation or infection. Patients undergoing EPBD were more likely to require mechanical lithotripsy for stone extraction (20.9% vs 14.8%, p = 0.014). On the basis of lower rates of bleeding, EPBD should be the preferred strategy over EST for endoscopic removal of common bile duct stones in patients with coagulopathy. Although EPBD is theoretically attractive for use in young patients for biliary sphincter preservation, the rate of pancreatitis is higher with EPBD and cannot be routinely recommended at this time.

Repair of defects in the common bile duct is hampered by a lack of healthy donor tissue. Developing human extrahepatic cholangiocyte organoids and testing them in mouse models may provide a way to overcome this limitation. The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties. We explore the regenerative potential of these organoids in vivo and demonstrate that ECOs self-organize into bile duct–like tubes expressing biliary markers following transplantation under the kidney capsule of immunocompromised mice. In addition, when seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary characteristics. The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs can successfully reconstruct the biliary tree, providing proof of principle for organ regeneration using human primary cholangiocytes expanded in vitro .

: Biliary tract injury remains the most dreaded complication during laparoscopic cholecystectomy. New intraoperative guidance technologies, including near-infrared (NIR) fluorescence cholangiography with indocyanine green (ICG), are under comprehensive evaluation. Previous studies had shown the limitations of traditional NIR light (NIR-I, 700-900 nm) in visualizing the biliary tract structures in specific clinical situations. The aim of this study was to evaluate the feasibility of performing the extrahepatic cholangiography in the second NIR window (NIR-II, 900-1700 nm) and compare it to the conventional NIR-I imaging. : The absorption and emission spectra, as well as fluorescence intensity and photostability of ICG-bile solution in the NIR-II window were recorded and measured. intralipid phantom imaging was performed to evaluate tissue penetrating depth in NIR-I and NIR-II window. Different clinical scenarios were modeled by broadening the penetration distance or generating bile duct injuries, and bile duct visualization and lesion site diagnosis in the NIR-II window were evaluated and compared with NIR-I imaging. : The fluorescence spectrum of ICG-bile solution extends well into the NIR-II region, exhibiting intense emission value and excellent photostability sufficient for NIR-II biliary tract imaging. Extrahepatic cholangiography using ICG in the NIR-II window obviously reduced background signal and enhanced penetration depth, providing more structural information and improved visualization of the bile duct or lesion location in simulated clinical scenarios, outperforming the NIR-I window imaging. : The conventional clinically approved agent ICG is an excellent fluorophore for NIR-II bile duct imaging. Fluorescence cholangiography with ICG in the NIR-II window could provide adequate visualization of the biliary tract structures with increased resolution and penetration depth and might be a valid option to increase the safety of cholecystectomy in difficult cases.

We describe in this review the different types of injuries caused to the biliary tree after liver transplantation. Furthermore, we explain underlying mechanisms and why oxygenated perfusion concepts could not only protect livers, but also repair high-risk grafts to prevent severe biliary complications and graft loss. Accordingly, we summarize experimental studies and clinical applications of machine liver perfusion with a focus on biliary complications after liver transplantation. Key points: (1) Acute inflammation with subsequent chronic ongoing liver inflammation and injury are the main triggers for cholangiocyte injury and biliary tree transformation, including non-anastomotic strictures; (2) Hypothermic oxygenated perfusion (HOPE) protects livers from initial oxidative injury at normothermic reperfusion after liver transplantation. This is a unique feature of a cold oxygenation approach, which is effective also end-ischemically, e.g., after cold storage, due to mitochondrial repair mechanisms. In contrast, normothermic oxygenated perfusion concepts protect by reducing cold ischemia, and are therefore most beneficial when applied instead of cold storage; (3) Due to less downstream activation of cholangiocytes, hypothermic oxygenated perfusion also significantly reduces the development of biliary strictures after liver transplantation.

Iatrogenic and traumatic bile leaks are uncommon. However, given the overall increase in number of hepatobiliary surgeries and the paradigm shift toward nonoperative management of patients with liver trauma, they have become more prevalent in recent years. Imaging is essential to establishing early diagnosis and guiding treatment as the clinical signs and symptoms of bile leaks are nonspecific, and a delay in recognition of bile leaks portends a high morbidity and mortality rate. Findings suspicious for a bile leak at computed tomography or ultrasonography include free or contained peri- or intrahepatic low density fluid in the setting of recent trauma or hepatobiliary surgery. Hepatobiliary scintigraphy and magnetic resonance cholangiopancreatography (MRCP) with hepatobiliary contrast agents can be used to detect active or contained bile leak. MRCP with hepatobiliary contrast agents has the unique ability to reveal the exact location of bile leak, which often governs whether endoscopic management or surgical management is warranted. Percutaneous transhepatic cholangiography and fluoroscopy via an indwelling catheter that is placed either percutaneously or surgically are useful modalities to guide percutaneous transhepatic biliary drain placement which can provide biliary drainage and/or diversion in the setting of traumatic biliary injury. Surgical treatment of a bile duct injury with Roux-en-Y hepaticojejunostomy is warranted if definitive treatment cannot be accomplished through percutaneous or endoscopic means.

Background Biliary leak following severe blunt liver injuries is a complex problem becoming more frequent with improvements in non-operative management. Standard treatment requires main bile duct drainage usually performed by endoscopic sphincterotomy and stent placement. We report our experience with cholecystostomy as a first minimally invasive diagnostic and therapeutic approach. Methods We performed a retrospective analysis of consecutive patients with post-traumatic biliary leak between 2006 and 2015. In the first period (2006–2010), biliary fistula was managed using perihepatic drainage and endoscopic, percutaneous or surgical main bile duct drainage. After 2010, cholecystostomy as an initial minimally invasive approach was performed. Results Of 341 patients with blunt liver injury, 18 had a post-traumatic biliary leak. Ten patients received standard treatment and eight patients underwent cholecystostomy. The cholecystostomy (62.5%) and the standard treatment (80%) groups presented similar success rates as the first biliary drainage procedure ( p  = 0.41). Cholecystostomy presented no severe complications and resulted, when successful, in a bile flow rate inversion between the perihepatic drains and the gallbladder drain within a median [IQR] 4 days [1–7]. The median time for bile leak resolution was 26 days in the cholecystostomy group and 39 days in the standard treatment group ( p  = 0.09). No significant difference was found considering median duration of hospital stay (54 and 74 days, respectively, p  = 0.37) or resuscitation stay (17.5 and 19.5 days, p  = 0.59). Conclusion Cholecystostomy in non-operative management of biliary fistula after blunt liver injury could be an effective, simple and safe first-line procedure in the diagnostic and therapeutic approach of post-traumatic biliary tract injuries.

Hepato-pancreato-biliary (HPB) injuries can be extremely challenging to manage. This scoping review (8438 citations) offers a number of recommendations. If diagnosis and therapy are rapid, patients with major hepatic injuries who present in physiologic extremis have high survival rates despite prolonged hospital stays. Nonoperative management of major liver injuries, as diagnosed using computed tomography, is typically successful. Adjuncts (e.g., angioembolization, laparoscopic washouts, biliary stents) are essential in managing high-grade injuries. Injury to the extrahepatic biliary tree is rare. Cholecystectomy is indicated for all gallbladder trauma. Full-thickness common bile duct injuries require a hepaticojejunostomy, although damage control remains closed suction drainage. Injuries to the pancreatic head often involve concurrent trauma to regional vasculature. Damage control necessitates drainage after stopping hemorrhage. Injury to the left pancreas commonly requires a distal pancreatectomy. Outcomes for high-grade pancreatic and liver injuries are improved by involving an HPB team. Complications are multidisciplinary and should be managed without delay.

Purpose To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. Methods Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4–75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100–300 μm beads loaded with ≤100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. Results: DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size ( p  < 0.0003) and a 56 % decrease in tumor enhancement ( p  < 0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. Conclusions Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.

Background The management of post-endoscopic retrograde cholangiopancreatography (ERCP) perforation is often unknown by many physicians, and there is a paucity of literature regarding the best surgical management approach. Patients and methods A retrospective review of ERCP-related perforations to the duodeno-pancreato-biliary tract observed at the Digestive Surgery Department of the Catholic University of Rome was conducted to identify their optimal management and clinical outcome. Results From January 1999 to December 2011, 30 perforations after ERCP were observed. Seven patients underwent ERCP at another institution, and 23 patients underwent an endoscopic procedure at our hospital. Diagnosis of perforation was both clinical and instrumental. Fifteen patients (50 %) were successfully treated conservatively. Fifteen patients (50 %) underwent surgery after a mean time of 8.1 days (range 1–26 days) from ERCP: ten received a retroperitoneal laparostomy approach, three of them both an anterior and posterior laparostomy approach, and two an anterior laparostomy approach. Duodenal leak closure was observed after a mean (±standard deviation, SD) of 12.6 (±4.6) and 24.6 (±7.9) days after conservative and surgical treatment, respectively ( p  < 0.001). The overall and postoperative mortality rates were 13.3 % (4 of 30 patients) and 26.6 % (4 of 15 patients), respectively. Conclusions Post-ERCP perforation is burdened by a high risk of mortality. Early clinical and radiographic features have to be used to determine which type of surgical or conservative treatment is indicated. Half of patients can be treated conservatively, but in case of sepsis or unstable general conditions, early surgical procedure is indicated as the only possible chance of recovery.

Alterations in the Wnt signaling pathway including those impacting hepatic stellate cells (HSCs) have been implicated in liver fibrosis. In the current study, we first examined the expression of Wnt genes in human HSC (HHSCs) after treatment with a profibrogenic factor TGF-β1. Next, we generated HSC-specific Wntless (Wls) knockout (KO) using the Lrat-cre and Wls-floxed mice. KO and littermate controls (CON) were characterized for any basal phenotype and subjected to two liver fibrosis protocols. In vitro, TGF-β1 induced expression of Wnt2, 5a and 9a while decreasing Wnt2b, 3a, 4, and 11 in HHSC. In vivo, KO and CON mice were born at normal Mendelian ratio and lacked any overt phenotype. Loss of Wnt secretion from HSCs had no effect on liver weight and did not impact β-catenin activation in the pericentral hepatocytes. After 7 days of bile duct ligation (BDL), KO and CON showed comparable levels of serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total and direct bilirubin. Comparable histology, Sirius red staining, and immunohistochemistry for α-SMA, desmin, Ki-67, F4/80, and CD45 indicated similar proliferation, inflammation, and portal fibrosis in both groups. Biweekly administration of carbon tetrachloride for 4 or 8 weeks also led to comparable serum biochemistry, inflammation, and fibrosis in KO and CON. Specific Wnt genes were altered in HHSCs in response to TGF-β1; however, eliminating Wnt secretion from HSC did not impact basal β-catenin activation in normal liver nor did it alter the injury-repair response during development of liver fibrosis.