Diseases of bile duct in children.

Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common disease of the bile duct in newborns is biliary atresia, whose prognosis varies according to the age of surgical correction. Other diseases such as Alagille syndrome, inspissated bile duct syndrome, and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction. The majority of these diseases present with cholestatic jaundice in the newborn or infant period, which is quite difficult to differentiate regarding clinical acumen and initial investigations. Intraoperative cholangiography is potentially necessary to make an accurate diagnosis, and further treatment will be performed synchronously or planned as findings suggest. This article provides a concise review of bile duct diseases, with interesting cases.

Non-operative management of biliary complications after Liver Transplantation in pediatric patients: A 30-year experience.

BACKGROUND: To evaluate the efficacy of percutaneous and endoscopic therapeutic interventions for biliary strictures and leaks following LT in children. METHODS: Retrospective analysis of 49 consecutive pediatric liver transplant recipients (27 girls, 22 boys, mean age at transplant 3.9 years) treated at our institution from 1989 to 2019 for biliary leak and/or biliary stricture was performed. Minimally invasive approach was considered clinically successful if it resulted in patency of the narrowed biliary segment and/or correction of the biliary leak. RESULTS: Forty-two patients had a stricture at the biliary anastomosis; seven had a biliary leak. After an average 13.8 years of follow-up, long-term clinical success with minimally invasive treatment (no surgery or re-transplant) was achieved for 24 children (57%) with biliary stricture and 4 (57%) with biliary leaks. Eight patients required re-transplant; however, only one was due to failure of both percutaneous and surgical management. For biliary strictures, failure of non-surgical management was associated with younger age at stricture diagnosis (p < .02). CONCLUSIONS: Percutaneous and endoscopic management of biliary strictures and leaks after LT in children is associated with a durable result in >50% of children.

Liver and Biliary Disease of Pregnancy and Anesthetic Implications: A Review.

Liver and biliary disease complicates pregnancy in varying degrees of severity to the mother and fetus, and anesthesiologists may be asked to assist in caring for these patients before, during, and after birth of the fetus. Therefore, it is important to be familiar with how different liver diseases impact the pregnancy state. In addition, knowing symptoms, signs, and laboratory markers in the context of a pregnant patient will lead to faster diagnosis and treatment of such patients. This review article discusses changes in physiology of parturients, patients with liver disease, and parturients with liver disease. Next, general treatment of parturients with acute and chronic liver dysfunction is presented. The article progresses to specific liver diseases with treatments as they relate to pregnancy. And finally, important aspects to consider when anesthetizing parturients with liver disease are discussed.

Routine versus selective intraoperative cholangiography during cholecystectomy: systematic review, meta-analysis and health economic model analysis of iatrogenic bile duct injury.

BACKGROUND: Bile duct injury (BDI) is a severe complication following cholecystectomy. Early recognition and treatment of BDI has been shown to reduce costs and improve patients' quality of life. The aim of this study was to assess the effect and cost-effectiveness of routine versus selective intraoperative cholangiography (IOC) in cholecystectomy. METHODS: A systematic review and meta-analysis, combined with a health economic model analysis in the Swedish setting, was performed. Costs per quality-adjusted life-year (QALY) for routine versus selective IOC during cholecystectomy for different scenarios were calculated. RESULTS: In this meta-analysis, eight studies with more than 2 million patients subjected to cholecystectomy and 9000 BDIs were included. The rate of BDI was estimated to 0.36 per cent when IOC was performed routinely, compared with to 0.53 per cent when used selectively, indicating an increased risk for BDI of 43 per cent when IOC was used selectively (odds ratio 1.43, 95 per cent c.i. 1.22 to 1.67). The model analysis estimated that seven injuries were avoided annually by routine IOC in Sweden, a population of 10 million. Over a 10-year period, 33 QALYs would be gained at an approximate net cost of €808 000 , at a cost per QALY of about €24 900. CONCLUSION: Routine IOC during cholecystectomy reduces the risk of BDI compared with the selective strategy and is a potentially cost-effective intervention.

Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.

Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium.

If It Looks Like a Duct and Acts Like a Duct: On the Role of Reprogrammed Hepatocytes in Cholangiopathies.

Cholangiopathies are chronic, progressive diseases of the biliary tree, and can be either acquired or genetic. The primary target is the cholangiocyte (CC), the cell type lining the bile duct that is responsible for bile modification and transport. Despite advances in our understanding and diagnosis of these diseases in recent years, there are no proven therapeutic treatments for the majority of the cholangiopathies, and liver transplantation is the only life-extending treatment option for patients with end-stage cholestatic liver disease. One potential therapeutic strategy is to facilitate endogenous repair of the biliary system, which may alleviate intrahepatic cholestasis caused by these diseases. During biliary injury, hepatocytes (HC) are known to alter their phenotype and acquire CC-like features, a process known as cellular reprogramming. This brief review discusses the potential ways in which reprogrammed HC may contribute to biliary repair, thereby restoring bile flow and reducing the severity of cholangiopathies. Some of these include modifying bile to reduce toxicity, serving as a source of de novo CC to repair the biliary epithelium, or creating new channels to facilitate bile flow.

Long-term outcomes after temporary placement of a self-expanding fully covered metal stent for benign biliary strictures secondary to chronic pancreatitis.

BACKGROUND AND AIMS: Temporary single, fully covered self-expanding metal stent (FCSEMS) placement for benign biliary strictures (BBSs) associated with chronic pancreatitis (CP) may require fewer interventions than endotherapy with multiple plastic stents and may carry less morbidity than biliary diversion surgery. This study aimed to assess long-term outcomes in CP-associated BBSs after FCSEMS placement and removal. METHODS: In this open-label, multinational, prospective study, subjects with CP and a BBS treated with FCSEMS placement with scheduled removal at 10 to 12 months were followed for 5 years after FCSEMS indwell. Kaplan-Meier analyses assessed BBS resolution and cumulative probability of freedom from recurrent stent placement to 5 years after FCSEMS indwell. RESULTS: One hundred eighteen patients were eligible for FCSEMS removal. At a median of 58 months (interquartile range, 44-64) post-FCSEMS indwell, the probability of remaining stent-free was 61.6% (95% confidence interval [CI], 52.5%-70.7%). In 94 patients whose BBSs resolved at the end of FCSEMS indwell, the probability of remaining stent-free 5 years later was 77.4% (95% CI, 68.4%-86.4%). Serious stent-related adverse events occurred in 27 of 118 patients (22.9%); all resolved with medical therapy or repeated endoscopy. Multivariate analysis identified severe CP (hazard ratio, 2.4; 95% CI, 1.0-5.6; P = .046) and longer stricture length (hazard ratio, 1.2; 95% CI, 1.0-1.4; P = .022) as predictors of stricture recurrence. CONCLUSION: In patients with symptomatic BBSs secondary to CP, 5 years after placement of a single FCSEMS intended for 10 to 12 months indwell, more than 60% remained asymptomatic and stent-free with an acceptable safety profile. Temporary placement of a single FCSEMS may be considered as first-line treatment for patients with CP and BBSs. (Clinical trial registration number: NCT01014390.).

Study of Recellularized Human Acellular Arterial Matrix Repairs Porcine Biliary Segmental Defects.

Background: With the popularity of laparoscopic cholecystectomy, common bile duct injury has been reported more frequently. There is no perfect method for repairing porcine biliary segmental defects. Methods: After the decellularization of human arterial blood vessels, the cells were cultured with GFP+ (carry green fluorescent protein) porcine bile duct epithelial cells. The growth and proliferation of porcine bile duct epithelial cells on the human acellular arterial matrix (HAAM) were observed by hematoxylin-eosin (HE) staining, electron microscopy, and immunofluorescence. Then, the recellularized human acellular arterial matrix (RHAAM) was used to repair biliary segmental defects in the pig. The feasibility of it was detected by magnetic resonance cholangiopancreatography, liver function and blood routine changes, HE staining, immunofluorescence, real-time quantitative PCR (RT-qPCR), and western blot. Results: After 4 weeks (w) of co-culture of HAAM and GFP+ porcine bile duct epithelial cells, GFP+ porcine bile duct epithelial cells grew stably, proliferated, and fused on HAAM. Bile was successfully drained into the duodenum without bile leakage or biliary obstruction. Immunofluorescence detection showed that GFP-positive bile duct cells could still be detected after GFP-containing bile duct cells were implanted into the acellular arterial matrix for 8 w. The implanted bile duct cells can successfully resist bile invasion and protect the acellular arterial matrix until the newborn bile duct is formed. Conclusion: The RHAAM can be used to repair biliary segmental defects in pigs, which provides a new idea for the clinical treatment of common bile duct injury.

Postoperative bleeding and biliary leak after liver resection: A cohort study between two different fibrin sealant patches.

Different topical products have been tested in liver resection to get a control of bleeding. This study compares the effectiveness and complications between two haemostatic agents Tachosil versus Hemopatch. A cohort study including patients who underwent liver resection since November 2014 to April 2016 was conducted. The study was performed in a single institution. Demographic variables, intraoperative characteristics and postoperative complications were analysed. A total of 92 patients (50 in Tachosil group and 42 in Hemopatch group) were included. No differences were found in patients who required intraoperative (Tachosil 6 (12%) vs Hemopatch 2 (4.8%); p = 0.28) and postoperative (Tachosil 4 (8%) vs Hemopatch 3 (7.1%); p = 0.87) blood transfusion. There were no differences in length of hospital stay (Tachosil 7.02 ± 4.1 days vs Hemopatch 7.63 ± 9.1; p = 0.67). Overall postoperative complications were similar between both patches (Tachosil 21 (42%) vs Hemopatch 14 (33%); p = 0.48). No differences were found in specific complications, however Hemopatch showed a higher incidence of intraabdominal abscess 5 (11.9%) and vs 0 (0%) p = 0.01.In this study no differences have been found between Hemopatch and Tachosil in the effectiveness and overall postoperative complication after liver resection, although Hemopatch shows a higher incidence of intraabdominal abscess. Further studies are necessary to confirm these findings.

Biliary Paracoccidioidomycosis: An Unusual Infection Simulating Malignant Neoplasm.

Paracoccidioidomycosis is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis and is restricted to Latin America. It normally affects lungs, skin and lymph nodes. Abdominal organs are usually not involved. In rare cases paracoccidioidomycosis may simulate neoplasm. Herein we describe our experience with four cases of paracoccidioidomycosis mimicking cholangiocarcinoma. To the best of our knowledge, this is the largest case series on this subject produced in English. Paracoccidioidomycosis must be considered as a differential diagnosis of cholangiocarcinoma, especially in individuals who come from endemic areas.

A retrospective clinical and microbial analysis of 32 patients with bilomas.

BACKGROUND: Bilomas are defined collections of bile fluids mainly caused by iatrogenic injuries of the bile duct system. Owing to the infrequency of this disease, studies addressing bilomas are rare. METHODS: By using an endoscopic database, this retrospective study identified 32 patients with bilomas treated between 2004 to 2015, in order to analyse aetiology, clinical presentation, spectrum of pathogens, and resolution rate of bilomas. RESULTS: 65.6% of the study population (21/32) developed bilomas after surgery and 21.9% (7/32) after endoscopic retrograde cholangiography (ERC). Icterus, fever, and abdominal pain were the leading symptoms. 93.9% (46/49) of microbiological bile cultures revealed a positive microbiology. The predominant microorganisms were the group of Enterobacteriaceae (43.0%, 52/121), followed by Enterococcus spp. (32.2%, 39/121), and Candida spp. (9.1%, 11/121). Multiresistant bacteria like Enterobacteriaceae were isolated from one quarter of all patients. Single or multimodal treatment resulted in an overall complication rate of 4.8% (9/188). Clinical follow-up analysis showed a complete resolution rate of 78.3% for interventional therapy and 80% in the non-interventional group. CONCLUSIONS: Pathogen spectrum of bilomas mainly comprises the group of Enterobacteriacae and Enterococcus spp., with a high proportion of multiresistant bacteria. Different interventional approaches are available for biloma drainage, which seem to be safe and effective for most patients. TRIAL REGISTRATION: German Clinical Trials Register DRKS00015208 , retrospectively registered.

Biliary interventions using single-operator cholangioscopy.

Cholangioscopy provides an opportunity to directly visualize the bile duct for diagnosing biliary lesions and for therapeutic interventions. Although there are different cholangioscopy techniques available, single-operator cholangioscopy has gained widespread acceptance as the standard technique for interventions in the biliary system because of its ease of use and widespread availability. Single-operator cholangioscopy can be used for both diagnostic and therapeutic indications in the biliary tract. Diagnostic cholangioscopy is used for direct evaluation of indeterminate bile duct strictures with biopsies, diagnosing filling defects in the bile ducts observed during endoscopic retrograde cholangiography (ERC) imaging, preoperative mapping of the precise location and extension of tumors of the biliary tract, and diagnosis of intraductal neoplasms. Therapeutic cholangioscopy is used for visually guided treatment of biliary stones that have failed extraction with conventional ERC techniques, residual or impacted stones by using intraductal lithotripsy, ablation of biliary tumors and for facilitation of guidewire advancement into selective intrahepatic ducts for adequate biliary drainage. In this review, we will focus on advances in the single-operator cholangioscopy techniques in the diagnosis and management of biliary disorders.