Can Microscopic Biliary Reconstruction Reduce Biliary Complication Rate in ABO-Incompatible Adult Living Donor Liver Transplantation?

BACKGROUND With the introduction of rituximab, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been considered a feasible and safe procedure to overcome the shortage of organ donors. However, higher biliary complication rates remain an unresolved problem in the ABOi group. In our center, biliary anastomosis has been done with microscopic biliary reconstruction (MBR), which effectively reduced the biliary complication rate. The aim of the current study was to investigate whether the microscopic approach reduced anastomotic biliary complications in ABOi LDLT. MATERIAL AND METHODS From March 2006 to December 2018, 30 adult ABOi and 60 ABO-compatible (ABOc) LDLT patients were selected from over 1300 recipients through 1: 2 propensity score-matched cohorts. All patients received MBR during the transplantation. Biliary complications included bile leakage and biliary stricture. Patients with diffuse intrahepatic biliary stricture were excluded from analysis. RESULTS Patient characteristics were similar in the 2 groups. There was no in-hospital mortality in the ABOi LDLT. The long-term survival rates of the ABOi patients were comparable to those of the patients that underwent ABOc LDLT (87.1% vs 87.4%, P=0.964). Those in the ABOi group with anastomotic biliary complications were about 40%, which was higher than in the ABOc patients (40% vs 15%, P=0.01). CONCLUSIONS Microscopic biliary reconstruction does not help to reduce the high biliary complication rate in ABOi LDLT. Further investigation and identification regarding other risk factors and precautionary measures involving immunologic and adaptation mechanisms are needed.

The Effect of Preoperative Biliary Drainage with or without Pancreatic Stenting on Complications after Pancreatoduodenectomy: A Retrospective Cohort Study.

BACKGROUND: The necessity of preoperative biliary drainage (PBD) prior to pancreaticoduodenectomy (PD) is still controversial. However, in some settings, PBD with endoscopic retrograde cholangiopancreatography (ERCP) procedure is recommended as a preferred management. Meanwhile, pancreatic duct stenting in the drainage procedure is rarely performed for selected indications, and its associated complications after PD remain quite unknown. METHODS: A retrospective observational longitudinal cohort study was performed on patients who underwent PBD and PD from a prospectively maintained database at the National Cancer Center from March of 2015 to July of 2019. Patients who underwent biliary stenting alone, biliary and pancreatic stenting, were distributed into two study cohort groups, and their records were scrutinized for the incidence of postoperative complications. RESULTS: A total of 83 patients who underwent successful PD after biliary drainage were identified. 29 patients underwent nasobiliary drainage (ENBD)/plastic or metal bile duct stenting (BS) and pancreatic duct stenting (PS group), and 54 patients underwent only ENBD/BS, without pancreatic duct stenting (NPS group). No differences were found between the two groups with respect to in-hospital time, overall complication rate, respective rate of serious (grade 3 or higher) complication rate, bile anastomotic leakage, bleeding, abdominal infection, surgical wound infection, organ dysfunction, and pancreatic anastomotic leakage. Postoperative gastrointestinal dysfunction rates differed significantly, which occurred in 3 (5.56%) cases in the NPS group, compared with 6 (20.7%) cases in the PS group (P = 0.06). In the univariate and multivariate regression model analysis, pancreatic duct stenting was correlated with higher rates of gastrointestinal dysfunction [odds ratio (OR) = 4.25, P = 0.0472]. CONCLUSION: Our data suggested that PBD and pancreatic duct stenting prior to pancreatoduodenectomy would increase the risk of postoperative delayed gastric emptying, while the overall incidence of postoperative complications and other complications, such as pancreatic leakage and bile duct leakage, showed no statistical difference.

Biliary cystadenoma: A rare occurrence.

Biliary cystadenoma is a rare benign tumour with the potential to transform into malignant carcinoma of the biliary ductal system. There is difficulty in differentiating a benign one from a malignant biliary cystadenoma, and therefore these lesions should always be completely resected. We report a case of biliary cystadenoma which underwent a complete resection.

Physical Activity Modulating Lipid Metabolism in Gallbladder Diseases.

Physical activity encompasses a series of overall benefits on cardiovascular health and metabolic disorders. Research has recently focused on the hepatobiliary tract, as an additional target of the health-related outcomes of different types of physical exercise. Here, we focus on the global features of physical activity with respect to exercise modality and intensity, and on studies linking physical activity to lipid metabolism, gallbladder diseases (gallstones, symptoms, complications and health-related quality of life), gallbladder motor-function, enterohepatic circulation of bile acids, and systemic metabolic inflammation. Additional studies need to unravel the pathophysiological mechanisms involved in both beneficial and harmful effects of physical activity in populations with different metabolic conditions.

TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function.

OBJECTIVE: We explored the hypothesis that TGR5, the bile acid (BA) G-protein-coupled receptor highly expressed in biliary epithelial cells, protects the liver against BA overload through the regulation of biliary epithelium permeability. DESIGN: Experiments were performed under basal and TGR5 agonist treatment. In vitro transepithelial electric resistance (TER) and FITC-dextran diffusion were measured in different cell lines. In vivo FITC-dextran was injected in the gallbladder (GB) lumen and traced in plasma. Tight junction proteins and TGR5-induced signalling were investigated in vitro and in vivo (wild-type [WT] and TGR5-KO livers and GB). WT and TGR5-KO mice were submitted to bile duct ligation or alpha-naphtylisothiocyanate intoxication under vehicle or TGR5 agonist treatment, and liver injury was studied. RESULTS: In vitro TGR5 stimulation increased TER and reduced paracellular permeability for dextran. In vivo dextran diffusion after GB injection was increased in TGR5-knock-out (KO) as compared with WT mice and decreased on TGR5 stimulation. In TGR5-KO bile ducts and GB, junctional adhesion molecule A (JAM-A) was hypophosphorylated and selectively downregulated among TJP analysed. TGR5 stimulation induced JAM-A phosphorylation and stabilisation both in vitro and in vivo, associated with protein kinase C-ζ activation. TGR5 agonist-induced TER increase as well as JAM-A protein stabilisation was dependent on JAM-A Ser285 phosphorylation. TGR5 agonist-treated mice were protected from cholestasis-induced liver injury, and this protection was significantly impaired in JAM-A-KO mice. CONCLUSION: The BA receptor TGR5 regulates biliary epithelial barrier function in vitro and in vivo through an impact on JAM-A expression and phosphorylation, thereby protecting liver parenchyma against bile leakage.

Peribiliary Gland Niche Participates in Biliary Tree Regeneration in Mouse and in Human Primary Sclerosing Cholangitis.

BACKGROUND AND AIMS: Mechanisms underlying the repair of extrahepatic biliary tree (EHBT) after injury have been scarcely explored. The aims of this study were to evaluate, by using a lineage tracing approach, the contribution of peribiliary gland (PBG) niche in the regeneration of EHBT after damage and to evaluate, in vivo and in vitro, the signaling pathways involved. APPROACH AND RESULTS: Bile duct injury was induced by the administration of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 14 days to Krt19Cre TdTomatoLSL mice. Human biliary tree stem/progenitor cells (BTSC) within PBGs were isolated from EHBT obtained from liver donors. Hepatic duct samples (n = 10) were obtained from patients affected by primary sclerosing cholangitis (PSC). Samples were analyzed by histology, immunohistochemistry, western blotting, and polymerase chain reaction. DDC administration causes hyperplasia of PBGs and periductal fibrosis in EHBT. A PBG cell population (Cytokeratin19- /SOX9+ ) is involved in the renewal of surface epithelium in injured EHBT. The Wnt signaling pathway triggers human BTSC proliferation in vitro and influences PBG hyperplasia in vivo in the DDC-mediated mouse biliary injury model. The Notch signaling pathway activation induces BTSC differentiation in vitro toward mature cholangiocytes and is associated with PBG activation in the DDC model. In human PSC, inflammatory and stromal cells trigger PBG activation through the up-regulation of the Wnt and Notch signaling pathways. CONCLUSIONS: We demonstrated the involvement of PBG cells in regenerating the injured biliary epithelium and identified the signaling pathways driving BTSC activation. These results could have relevant implications on the pathophysiology and treatment of cholangiopathies.

Imaging of Acute Hepatobiliary Dysfunction.

Abdominal pain is a common cause for emergency department visits in the United States, and biliary tract disease is the fifth most common cause of hospital admission. Common causes of acute hepatobiliary include gallstones and its associated complications and multiple other hepatobiliary etiologies, including infectious, inflammatory, vascular, and neoplastic causes. Postoperative complications of the biliary tract can result in an acute abdomen. Imaging of the hepatobiliary tree is integral in the diagnostic evaluation of acute hepatobiliary dysfunction, and imaging of the biliary tree requires a multimodality approach utilizing ultrasound, computed tomography, nuclear medicine, and MR imaging.

Evaluation of a three-session biliary dilation protocol following transplant-related biliary stricture in pediatric patients.

To evaluate whether a serial biliary dilation protocol improves outcomes and decreases total biliary drainage time for biliary strictures following pediatric liver transplantation. From 2006 to 2016, 213 orthotopic deceased and living related liver transplants were performed in 199 patients with a median patient age of 3.1 years at a single pediatric hospital. Patients with biliary strictures were managed by IR or surgically by the transplant team. Patients managed by IR were divided into two groups. The first group was managed with a standardized three-session protocol consisting of dilation every two weeks for three dilations. The second group was managed clinically with varying number and interval of dilations as determined by a multidisciplinary team. The location of biliary stricture, duration of drainage, number of balloon dilations, balloon diameter, time interval between dilations, and success of percutaneous treatment were recorded. Thirty-four patients developed biliary strictures. Thirty-one patients were managed with percutaneous intervention. Three strictures could not be crossed and were converted to operative management. Ten patients were managed in the three-session protocol, and 18 patients were managed in the clinically treated group. There was no significant difference in clinical success rates between groups, 80% and 61%, respectively. The three-session protocol group trended toward a lower total biliary drain indwell time (median 49 days) compared with the clinically treated group (median 89 days), P = .089. Our study suggests that a three-session dilation protocol following transplant-related biliary stricture may decrease total biliary drainage time for some patients.

Human Liver Regeneration: An Etiology Dependent Process.

Regeneration of the liver has been an interesting and well-investigated topic for many decades. This etiology and time-dependent mechanism has proven to be extremely challenging to investigate, certainly in human diseases. A reason for this challenge is found in the numerous interactions of different cell components, of which some are even only temporarily present (e.g., inflammatory cells). To orchestrate regeneration of the epithelial cells, their interaction with the non-epithelial components is of utmost importance. Hepatocytes, cholangiocytes, liver progenitor cells, and peribiliary glands have proven to be compartments of regeneration. The ductular reaction is a common denominator in virtually all liver diseases; however, it is predominantly found in late-stage hepatic and biliary diseases. Ductular reaction is an intriguing example of interplay between epithelial and non-epithelial cells and encompasses bipotential liver progenitor cells which are able to compensate for the loss of the exhausted hepatocytes and cholangiocytes in biliary and hepatocytic liver diseases. In this manuscript, we focus on the etiology-specific damage that is observed in different human diseases and how the liver regulates the regenerative response in an acute and chronic setting. Furthermore, we describe the importance of morphological keynotes in different etiologies and how spatial information is of relevance for every basic and translational research of liver regeneration.

Sublingual microcirculation in pancreatico-biliary surgery: An observational study.

BACKGROUND: An observational cohort study was conducted to identify potential sublingual microcirculation parameters as a target for goal-directed fluid therapy. METHODS: Patients that were scheduled for an open elective pancreatico-biliary surgery in Erasmus Medical Center were included. All patients underwent sublingual microcirculatory measurement at three time points: one day before surgery (T0), within the first 24 hours after surgery (T1) and on the fourth day after surgery (T2). The following parameters were obtained: microvascular flow index (MFI (AU)), Total vessels density (TVD (mm/mm2/)), Perfused vessels density (PVD (mm/mm2)), and proportion of perfused vessels (PPV (%)). RESULTS: Sixteen patients were included in the final analysis. The differences between the time points T1 and T0 in patients without clinical significant complication and in patients with these complications gave a significant difference for PVD small vessels (PVDs) (delta PVDs mean -0.1 vs -8.2, p=0.01) and PPV small vessels (PPVs) (delta PPVs median 7.0 % vs -15.5 %, p=0.01). CONCLUSION: The most significant microcirculatory parameter for a perioperative complicated course is the change of PVD and PPV. In the first 24 hours after surgery, if these parameters decrease there is a high chance of a complicated perioperative course.

Ultrasound Assessment of Hepatobiliary and Splenic Changes in Patients With Dengue and Warning Signs During the Acute and Recovery Phases.

OBJECTIVES: To evaluate whether abdominal ultrasound (US) with a gallbladder (GB) contractility study or motor function test can be used as a diagnostic tool in patients with dengue and warning signs in acute and recovery phases. METHODS: Fifty-one individuals in the acute phase of dengue presenting with warning signs (dengue group) and 49 healthy individuals without a history of dengue or hepatobiliary disease (control group) were studied with abdominal US and a GB contractility study. RESULTS: Statistical differences in US measurements of the liver (right lobe, P = .012; left lobe, P = .001) and spleen (P = .008) dimensions, GB wall thickness (P < .001), and the GB emptying fraction (P < .001) were observed in dengue during the acute phase compared with the control group. After 60 days, abdominal US of the dengue group showed a statistical difference in liver (right lobe, P < .001; left lobe, P = .078) and spleen (P < .001) dimensions, GB wall thickness, and the GB emptying fraction (P < .001) compared with the results obtained during the acute phase. Furthermore, a statistical difference in the spleen volume and GB emptying fraction (P < .001) was observed when comparing dengue after clinical recovery and the control group. Abdominal pain in patients with dengue was positively associated with hepatomegaly (P = .031), splenomegaly (P = .008), increased GB wall thickness (P = .016), and a reduced GB emptying fraction (P = .038) during the acute phase and with splenomegaly (P = .001) and a reduced GB emptying fraction (P = .003) after clinical recovery. CONCLUSIONS: Abdominal US with a GB motor function test can be used as a diagnostic tool in patients with dengue during acute and recovery phases.

Pathophysiological consequences of obstructive jaundice and perioperative management.

BACKGROUND: Obstructive jaundice is a common problem in daily clinical practice. Understanding completely the pathophysiological changes in obstructive jaundice remains a challenge for planning current and future management. DATA SOURCES: A PubMed was searched for relevant articles published up to August 2016. The effect of obstructive jaundice on proinflammatory cytokines, coagulation status, hemodynamics and organ functions were evaluated. RESULTS: The effects of obstructive jaundice included biliary tree, the hepatic cell and liver function as well as systemic complications. The lack of bile in the gut, the disruption of the intestinal mucosal barrier, the increased absorption of endotoxin and the subsequent endotoxemia cause proinflammatory cytokine production (TNF-α, IL-6). Bilirubin induces systemic inflammatory response syndrome which may lead to multiple organ dysfunction syndrome. The principal clinical manifestations include hemodynamic instability and acute renal failure, cardiovascular suppression, immune compromise, coagulation disorders, nutritional impairment, and wound healing defect. The proper management includes full replacement of water and electrolyte deficiency, prophylactic antibiotics, lactulose, vitamin K and fresh frozen plasma, albumin and dopamine. The preoperative biliary drainage has not been indicated in overall, but only in a few selected cases. CONCLUSION: The perioperative management is an essential measure in improving the outcome after the appropriate surgical operation in jaundiced patients especially those with malignancy.

Fatal Elizabethkingia MeningosepticaCholangitis Following Biliary Stent Placement.

Elizabethkingia (E.) meningosepticais a ubiquitous gram-negative bacillus belonging to the genus Chryseobacteriumand has been reported to cause nosocomial infections in both the immunocompromised and immunocompetent patients. E. meningoseptica can colonize the biliary tree after endoscopic procedures; and cholangitis, caused by this organism, is associated with a favorable prognosis. Here, we report a fatal case of cholangitis secondary to E. meningoseptica that developed following biliary stent placement. This case suggests that E. meningoseptica can be a cause of potentially fatal biliary tract infections in patients who undergo biliary tract endoscopic procedures. Clinicians must not disregard this organism as a contaminant (or colonizer) as a delay in diagnosis and treatment can lead to a fatal outcome, as seen in this case.

Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A case-control study.

BACKGROUND/OBJECTIVE: The potential benefit of preoperative biliary drainage (PBD) on postoperative outcomes remains controversial. The aim of this study was to elucidate surgical outcomes of pancreaticoduodenectomy (PD) in patients with PBD and to show the impact of bilirubin level. METHODS: We retrospectively studied all patients who underwent PD in our center between January 2003 and June 2015. Patients were divided into: Group A (PBD) and Group B (no PBD). The primary outcome was the rate of postoperative complication. RESULTS: A total of 588 cases underwent PD. Group A included 314 (53.4%) patients while Group B included 274 (46.6%) patients. The overall incidence of complications and its severity were higher in Group A (p = 0.03 and p = 0.02). There was significant difference in the incidence of postoperative pancreatic fistula (p = 0.002), delayed gastric emptying (p = 0.005), biliary leakage (p = 0.04), abdominal collection (p = 0.04), and wound infection (p = 0.04) in Group A. The mean length of hospital stay was significantly longer in Group A than in Group B (12.86 ± 7.65 days vs. 11.05 ± 7.98 days, p = 0.01). No significant impact of preoperative bilirubin level on surgical outcome was detected. CONCLUSION: PBD before PD was associated with major postoperative complications and stent-related complications.

Cope's sign and complete heart block in a 78-year-old patient with biliary colic.

INTRODUCTION: Acute cholecystitis and biliary colic may have signs and symptoms similar to those of Acute Coronary Syndrome(ACS) along with ischemic ECG changes. Cholecystitis and/or biliary colic have been both reported as trigger factors for bradyarrhythmia in the literature. CASE REPORT: A 78-year-old male patient was admitted to our Emergency Department (ED) due to acute abdominal pain. The ECG on admission showed sinus bradycardia with a rate of 40 beats per minute (bpm) without signs of acute ischemia and a brief period (7 s) of complete atrioventricular (AV) block. He was initially treated with analgesics. After the remission of the pain, a subsequent ECG was performed which showed sinus bradycardia of 55 bpm. The AV block terminated one hour after the patient's admission. The patient remained hemodynamically stable during the episode. He underwent an ultrasound of the abdomen in the ED which revealed sludge and one stone in the gallbladder without signs of inflammation. Laboratory test results for D-dimer and troponin were negative, while the coronary angiography showed coronary vessels without significant lesions. CONCLUSION: Biliary colic can cause severe reversible reflex bradycardia (Cope's Sign), even complete heart block. Pain relief is very important in the management of such cases.

[Inflammatory and neoplastic cholangiopathies.] / Colangiopatie infiammatorie e neoplastiche.

The biliary tree consists of mature epithelial cells called cholangiocytes and is subdivided in intra and extrahepatic bile ducts. They facilitate the secretion and modification of the bile constituents and act as transport ducts of bile to the intestine. The alteration of the normal function of cholangiocyte, can lead to the development of multiple biliary diseases, known as cholangiopathies, generally chronic, with a progressive course and which often are lacking of an effective treatment, determining a poor prognosis, even lethal, for the patient. These cholangiopathies have peculiar characteristics both for onset and clinical course. The pathogenetic processes affecting cholangiocytes are not yet fully known. Depending on their nature, these diseases are further subdivided into genetic, idiopathic, which include primary biliary cholangitis, primary sclerosing cholangitis and associated IgG4 cholangitis and malignant such as cholangiocarcinoma or mixed hepato-cholangiocarcinoma. This review is focused on the new insights on the pathophysiological and molecular mechanisms involved in the liver damage cascade which provide the basis of novel therapeutic approaches for these cholangiopathies.

Biliary system architecture: experimental models and visualization techniques.

The complex architecture of the liver biliary network represents a structural prerequisite for the formation and secretion of bile as well as excretion of toxic substances through bile ducts. Disorders of the biliary tract affect a significant portion of the worldwide population, often leading to cholestatic liver diseases. Cholestatic liver disease is a condition that results from an impairment of bile formation or bile flow to the gallbladder and duodenum. Cholestasis leads to dramatic changes in biliary tree architecture, worsening liver disease and systemic illness. Recent studies show that the prevalence of cholestatic liver diseases is increasing. The availability of well characterized animal models, as well as development of visualization approaches constitutes a critical asset to develop novel pathogenetic concepts and new treatment strategies.

Percutaneous interventional management of biliary complications after pediatric liver transplantation: A 16-year single-institution experience.

The aim of the study was to investigate the BiCx after the pediatric OLT and to assess the efficacy of the fluoroscopic-guided PBI in the patients with BiCx as compared to the SR. A total of 340 OLTs were performed in 302 patients over the last 16 years. The inclusion criteria were the presence of BS or BL as a complication after OLT. The management of the BiCx was studied. Graft revision, graft loss, and survival were evaluated following PBI and SR. BiCx occurred in 17.1% (58/339) of the transplants; 6.2% (21/339) of transplants demonstrated BL and 12.7% (43/339) of the transplants had BS. Overall graft survival rates at 1 and 3 years in OLT with BL treated with PBI were 75.0% and 68.8% as compared with 75% and 66.7% in OLT treated with SR (P>.05). Overall graft survival rates at 1 and 3 years in OLT with BS treated with PBI were 70.6% and 54.5% as compared with 71.4% and 50% in OLT with SR or ERCP, respectively (P>.05). Based on the results, we conclude that PBI is as effective as SR in patients with the BL and BS after OLT.

Biliary tract enhancement in gadoxetic acid-enhanced MRI correlates with liver function biomarkers.

PURPOSE: To evaluate the association between gadoxetic-acid-enhanced magnetic resonance (MR) imaging measurements and laboratory and clinical biomarkers of liver function and fibrosis. MATERIALS AND METHODS: One hundred thirty nine consecutive patients with suspected liver disease or liver tumor underwent gadoxetic-acid-enhanced MR imaging. MR imaging measurements during the hepatobiliary phase included biliary tract structure-to-muscle signal intensity ratio (SIR). These measurements were compared with Child-Pugh classification, end-stage liver disease (MELD) score, and aspartate aminotransferase-to-platelet ratio index (APRI). RESULTS: The SIRs of cystic duct and common bile duct were significantly correlated with Child-Pugh classification (P=0.012 for cystic duct and P<0.0001 for common bile duct), MELD score (P=0.0016 and P=0.0033), and APRI (P=0.0022 and P=0.0015). The sensitivity, specificity, and area under the receiver-operating-characteristic curve were: (74%, 88%, 0.86) with the SIR of common bile duct for the detection of patients with Child-Pugh class B or C; (100%, 87%, 0.94) with the SIR of cystic duct for MELD score (>10); (65%, 76%, 0.70) with the SIR of common bile duct for APRI (>1.5). CONCLUSION: Gadoxetic-acid contrast enhancement of cystic duct and common bile duct could be used as biomarkers to assess liver function.