Bile duct anatomical variations: Relevance for liver division and preparing left split liver grafts for pediatric transplantation: Cohort study.

BACKGROUND: liver lateral section graft is the most common graft type used for transplantation in children worldwide. Compared to whole liver grafts, a higher rate of biliary complications has been described. Historically, 2 techniques have been described for transection of liver - trans-hilar or trans-umbilical parenchymal transection. Though these techniques allow dividing the biliary system at two distinct positions, the usual surgical strategies do not take advantage of this advantage. MATERIAL AND METHODS: A retrospective study was conducted on 40 candidates who volunteered for donation of their left lateral liver section for transplantation, between October 2017 and April 2019. Preoperative imaging was analyzed to depict the arterial and biliary anatomy of the liver and their variations, with a dedicated attention to the left liver (segments 2, 3 and 4). Anatomy of the biliary system was taken into account for defining the optimal surgical strategy - either through a trans-hilar or a trans-umbilical parenchymal transection. RESULTS: In 26/40 patients, arterial or biliary variations were much relevant for decision-making on the optimal plane of liver division (trans-umbilical (N = 14) and trans-hilar (N = 26)). This resulted in 23 grafts with a single artery and bile duct, 6 grafts with double arteries and a single bile duct, and 9 grafts with double bile ducts and a single artery; only two grafts had complex anatomy. There was no arterial complication and the overall incidence of biliary problems was 14.7%. All grafts are functioning well at a mean follow-up of 19.6 ± 8.5 months. CONCLUSIONS: Anatomical variations are frequent and their knowledge is relevant for procurement of lateral section liver graft. Knowledge of these variation, or -better- preoperative biliary imaging is helpful in guiding parenchymal transection at procurement and preparing optimal liver grafts.

Imaging post liver transplantation part II: biliary complications.

Biliary complications post liver transplantation are a significant source of morbidity and mortality and early recognition is paramount to the long-term success of the liver graft. Part II of this series will focus on liver transplant biliary anatomy, including the blood supply to the biliary system and potential problems if it is interrupted. The imaging rationale for investigating suspected biliary complications, potential pitfalls, and treatment options will be discussed. The various biliary complications will be illustrated using a collection of cases.

Radiological findings in ischaemic cholangiopathy.

Ischaemic cholangiopathy occurs as a consequence of deficient arterial blood flow to the bile duct wall. Bile duct ischaemia can lead to full-thickness necrosis, bile leakage, biloma formation, and sepsis. It is an important cause of graft failure post-orthotopic liver transplantation. In the native liver, the causes of biliary ischaemia are diverse and include vasculitis or a complication of endovascular procedures. The present review describes the pathology and radiological findings of ischaemic cholangiopathy and outlines the role of interventional radiology in its management.

Heterogeneity of Bile Duct Management in the Development of Ischemic Cholangiopathy After Liver Transplantation: Results of a European Liver and Intestine Transplant Association Survey.

BACKGROUND: Surgical factors and direct cytotoxicity of bile salts on cholangiocytes may play a role in the development of ischemic cholangiopathy (IC) after liver transplantation (LTx). There is no validated consensus on how to protect the bile ducts during procurement, static preservation, and LTx. Meanwhile, IC remains the most troublesome complication after LTx. AIM: To characterize bile duct management techniques during the LTx process among European transplant centers in cases of donation after brain death (DBD) and circulatory death (DCD). METHOD: An European Liver and Intestine Transplant Association-European Liver Transplant Registry web survey designed to conceal respondents' personal information was sent to surgeons procuring and/or transplanting livers in Europe. RESULTS: Sixty-five percent of responses came from large transplant centers (>50 procurements/y). In 8% of DBDs and 14% of DCDs the bile duct is not rinsed. In 46% of DBDs and 52% of DCDs surgeons prefer to remove the gallbladder after graft reperfusion. Protocols concerning preservation solutions (nature, pressure, volume) are extremely heterogeneous. In 54% of DBDs and 61% of DCDs an arterial back table pressure perfusion is performed. Steroids (20%-10%), heparin (72%-60%), prostacyclin (3%-7%), and fibrinolytics (4%-11%) are used as donor-protective interventions in DBD and DCD cases, respectively. In 2% of DBD and 6% of DCD cases a hepatic artery reperfusion is performed first. In 4% of DBD and 6% of DCD cases, fibrinolytics are administered through the hepatic artery during the bench and/or implantation. CONCLUSION: This European web survey shows for the first time the heterogeneity in the management of bile ducts during procurement, preservation, and transplantation in Europe. In the context of sharing more marginal liver grafts, an expert meeting must be organized to formulate guidelines to be applied to protect liver grafts against IC.

Ischemic Cholangiopathy: Insight From an Explant Liver Allograft Affected by Severe Post-transplant Hypoxemia Due to Hepatopulmonary Syndrome: A Case Report.

Increased biliary complications in hepatopulmonary syndrome (HPS) have been hypothesized due to post-transplant hypoxemia. Supporting this hypothesis, we report histopathological findings from an explant liver allograft where the recipient suffered severe and prolonged post-operative hypoxemia. A 4-year-old child underwent liver transplantation (LT) for decompensated chronic liver disease complicated by severe HPS. The post-operative period was complicated by severe prolonged hypoxemia. HPS resolved completely 6 months after LT only to recur 3 months later due to graft dysfunction. The child underwent retransplantation 8 months after the first LT. The explant liver showed bile duct loss along with ulceration and fibrosis of large hilar bile ducts biliary, suggestive of ischemic cholangiopathy. Based on the histopathology findings, we suggest that severe prolonged hypoxemia during post-transplant period could cause ischemic cholangiopathy, which can lead to biliary complications.

Extending resectability of hilar cholangiocarcinomas: how can it be assessed and improved?

Until the 1980's, Klatskin tumors were considered 'desperate cases' and most of them were not resected; almost no oncologic concept was available. After many improvements, today, extended hepatectomy, including caudate lobe resection and lymphoadenectomy, have become a standard of care for oncologicaly radical resection of Klatskin tumors. Portal vein en bloc resection, if necessary, is a diffused standard assuring R0-resection without any improvement of survival in most series. Arterial resection remains episodical and controversial in its oncologic impact. Arterial resection-reconstruction was demonstrated to be feasible with many different technical possibilities. Neoadjuvant chemotherapy, refinement of associating liver partition and portal vein ligation for staged hepatectomy and liver transplantations are some possible future resources for treatment of those aggressive tumors that could be able to expand the pool of treatable patients.

In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival.

Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from whom 43 livers were transplanted. These were compared with 187 non-NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs. 32% for non-NRP livers, P = .0076), 30-day graft loss (2% NRP livers vs. 12% non-NRP livers, P = .0559), freedom from ischemic cholangiopathy (0% vs. 27% for non-NRP livers, P < .0001), and fewer anastomotic strictures (7% vs. 27% non-NRP, P = .0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (P < .0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.

[Hepatocellular Carcinoma with Bile Duct Thrombosis - A Case Report].

Hepatocellular carcinoma(HCC)is not commonly observed with bile duct thrombosis.Here, we report a case of HCC with bile thrombi that extended to the liver hilum.The patient was a 61-year-old man who visited us due to untreated type B hepatitis.He underwent screening with a CT scan that revealed LDA on the right posterior lobe of his liver with infiltration of the bile duct.Generally, bile resection and reconstruction should be considered for curative resection for bile thrombi; however, we attempted to conserve the common bile duct to preserve the options of percutaneous therapy in case of tumor recurrence.We performed right lobectomy of the liver.The bile duct thrombus was extracted without bile duct resection or reconstruction.The patient is alive 6 months after the surgery without any development.

Clinical Analysis of Classification and Prognosis of Ischemia-Type Biliary Lesions After Liver Transplantation.

BACKGROUND The aim of this study was to classify ischemia-type biliary lesions after liver transplantation according to their imaging findings and severity of clinical manifestations and to analyze the relationship between such classification and prognosis. MATERIAL AND METHODS We collected clinical data of patients with ischemia-type biliary lesions (ITBL) after liver transplantation in the Organ Transplantation Center, the First Central Hospital of Tianjin, from August 2012 to July 2013; all patients were classified according to their imaging findings and relevant clinical data to analyze the relationship between their classification and prognosis. RESULTS The mean postoperative survival time, as well as the 1-, 3-, and 5-year survival rate, in Group ITBL showed statistical significance when compared with those in Group NITBL (log rank=12.13, P<0.001), but the mean postoperative survival times among the mild, moderate, and severe ITBL cases showed no statistical significance. The incidence rates of 1-, 3-, and 5-year adverse prognosis in Group ITBL showed statistical significance when compared with Group NITBL with <2% patients who had anastomotic biliary obstruction (log rank=277.06, P<0.001), among which the difference in the incidence rate of adverse prognosis between severe and moderate ITBL cases showed no statistical significance. The difference in the incidence rate of adverse prognosis between mild and moderate ITBL cases showed statistical significance (log rank=6.01, P=0.014), and the difference in the incidence rate of adverse prognosis between mild and severe ITBL cases showed statistical significance (log rank=10.98, P=0.001). CONCLUSIONS ITBL classification based on the severity of biliary imaging and bilirubin level can predict the prognosis of ITBL.

Bile duct angulation and tumor vascularity are useful radiographic features for differentiating pancreatic head cancer and intrapancreatic bile duct cancer.

BACKGROUND AND PURPOSE: To perform radical resection without leaving residual cancer, surgeons must distinguish between pancreatic head cancer (PHC) and intrapancreatic bile duct cancer (IPBDC) preoperatively. The aim of this study was to establish the points of difference between these two cancers, especially on preoperative multi-detector computed tomography (MDCT) images. METHODS: The subjects of this study were 28 patients with PHC and proven bile duct invasion who underwent pancreatoduodenectomy (PHC group) and 22 patients with IPBDC and upstream bile duct dilation (IPBDC group). We compared the preoperative clinical and radiographic features, including the bile duct angle, calculated on coronal images of MDCT, and the vascularity of the tumor. RESULTS: The optimal cut-off values for the bile duct angle, the CT value ratio of the tumor (late arterial phase/non-enhanced), and the main pancreatic duct (MPD) ratio (diameter of MPD/diameter of parenchyma) were 110°, 3.0, and 0.2, respectively. Multivariate analysis revealed that a bile duct angle < 110°, a CT value ratio of the tumor < 3, and an MPD ratio ≥ 0.2 were independently associated with PHC. CONCLUSIONS: A bile duct angle and CT value reflecting the vascularity of the tumor might be useful radiographic features for differentiating PHC and IPBDC, in addition to MPD dilatation.

S-Adenosylmethionine attenuates bile duct early warm ischemia reperfusion injury after rat liver transplantation.

Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 µmol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (P < .05). Simultaneously, SAM effectively improved the survival of the transplant recipients. Furthermore, the H2O2 and malondialdehyde (MDA) of the IRI group were much higher compared to the SAM group (P < .05). The GSH/GSSG ratio in the SAM group was significantly increased by SAM treatment compared to the IRI group (P < .05). SAM administration significantly inhibited macrophage infiltration in liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (P < .05). The number of apoptotic biliary epithelial cells and caspase-3-positive cells in IRI rat livers were much higher compared to those in SAM-treated rats at 24 h after liver transplantation (P < .05). These data suggested that SAM protected bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α.

Effect of heme oxygenase-1 on the protection of ischemia reperfusion injury of bile duct in rats after liver transplantation.

OBJECTIVE: To investigate the effect of heme oxygenase-1 (HO-1) on the ischemic reperfusion injury (IRI) of bile duct in rat models after liver transplantation. METHODS: 320 SD rats were equally and randomly divided into 5 groups, which were group A receiving injection of 3×108/pfu/ml adenovirus (adv), group B with donor receiving Adv-HO-1 and recipient receiving Adv-HO-1-siRNA, group C with donor and recipient both receiving Adv-HO-1, group D with donor receiving Adv-HO-1-siRNA and recipient receiving Adv-HO-1, and group E with donor and recipient both receiving Adv-HO-1-siRNA at 24h before liver transplantation. Donor liver was stored in UW liquid at 4°C followed by measuring HO-1 level by western blot before transplantation. On d1, d3, d7 and d14, serum and liver was isolated for analysis of liver function, inflammatory cell infiltration by H&E staining, ultrastructure of liver by transmission electron microscopy as well as the expression of HO-1, Bsep, Mrp2 and Ntcp by western blot. RESULTS: Compared with group D and E, group B and C displayed improved liver function as demonstrated by lower level of ALT, AST, LDH, TBIL, ALP and GGT, increased secretion of TBA and PL as well as expression of transporter proteins (Bsep, Mrp2 and Ntcp), reduced inflammatory cells infiltration and liver injury. CONCLUSION: Our study demonstrated that overexpression of HO-1 in donor liver can ameliorate the damage to bile duct and liver, and improved liver function, suggesting HO-1 might be a new therapeutic target in the treatment of IRI after liver transplantation.

Hepatic or Cystic Artery Pseudoaneurysms Following a Laparoscopic Cholecystectomy: Literature review of aetiopathogenesis, presentation, diagnosis and management.

Pseudoaneurysms (PSAs) of the hepatic and/or cystic artery are a rare complication following a laparoscopic cholecystectomy (LC). Generally, PSA cases present with haemobilia several weeks following the procedure. Transarterial embolisation (TAE) is considered the optimal management approach. We report a 70-year-old woman who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2016 with massive hemoperitoneum two weeks after undergoing a LC procedure in another hospital. She was successfully managed using coil TAE. An extensive literature review revealed 101 cases of hepatic or cystic artery PSAs following a LC procedure. Haemobilia was the main presentation (85.1%) and the mean time of postoperative presentation was 36 days. The hepatic artery was involved in most cases (88.1%), followed by the cystic artery (7.9%) and a combination of both (4.0%). Most cases were managed with TAE (72.3%), with a 94.5% success rate. The overall mortality rate was 2.0%.

[Analysis of clinical prognosis and the correlation between bile duct injury after transcatheter arterial chemoembolization and the level of hepatic arterial embolization in patients with hepatocellular carcinoma].

Objective: To evaluate the correlation between bile duct injury after transcatheter arterial chemoembolization and the level of hepatic arterial embolization, and to analyze the clinical prognosis of hepatocellular carcinoma patients. Methods: From January18, 2012 to December18, 2014, 21 patients underwent TACE for HCC were retrospectively reviewed, including patients' clinical and pathological data. The clinical outcome and relevant factors for bile duct injury were analyzed. Results: A total of 21 patients were identified with bile duct injury at our single institution. All patients received 48 TACE treatments, including proper hepatic artery (14), left hepatic artery (3), the right hepatic artery (10), left and right hepatic artery (9) and tumor artery branches (12). Thirty-five bile duct injury occurred in 21 patients: 7 cases was close to the tumor, 2 distant to the tumor, 7 at right liver, 2 left liver, 11 both lobes of liver and 6 hepatic hilar. After medical conservative treatment and biliary tract inside and outside drainage, liver function of 10 cases were improved. In four patients with hepatic bile duct stricture and biloma, the effect of drainage was not obvious, which subsequently caused biliary complications such as infection, gallbladder and common bile duct stones. Three patients with liver cirrhosis at decompensation stage developed complications, and one of them died of hepatic encephalopathy. Four patients experienced tumor recurrence during the follow-up period. Conclusions: The location of bile duct injury after transcatheter arterial chemoembolization is quite consistent with the level of hepatic arterial embolization. There may be some blood vessels mainly involved in blood supply of biliary duct. Complete embolism of these vessels may lead to bile duct injuries. Biliary drainage is ineffective in patients with hilar bile duct stricture, and can lead to complications of biliary tract later on.

Low-Dose Lipopolysaccharide Causes Biliary Injury by Blood Biliary Barrier Impairment in a Rat Hepatic Ischemia/Reperfusion Model.

This study explored whether bacterial endotoxins, in the form of lipopolysaccharides (LPS), could have an injurious effect on the biliary tract in conjunction with ischemia. A total of 64 rats were randomly assigned to 4 groups: sham operation (sham group), 1 mg/kg LPS intraperitoneal (LPS group), hepatic ischemia/reperfusion (IR; IR group), and IR combined with LPS (IR+LPS group). Following 1 or 6 hours of reperfusion, serum liver tests, bile duct histology, immunofluorescence microscopy (zonula occludens-1 [ZO-1]), bile composition (bile salts, phospholipids, lactate dehydrogenase), hepatic gene expression (bile salt transporters and inflammatory mediators), as well as serum and biliary cytokine concentrations were quantified and compared between the study groups. In addition, the integrity of the blood biliary barrier (BBB) was assayed in vivo using horseradish peroxidase (HRP). LPS administration induced severe small bile duct injury following 6 hours of reperfusion. Furthermore, total bile salts and bilirubin concentrations in serum were increased in the LPS groups compared with sham controls (LPS, + 3.3-fold and +1.9-fold; IR+LPS, + 3.8-fold and +1.7-fold, respectively). The BBB was impaired in the LPS groups as evidenced by elevated levels of HRP in bile (+4.9-fold), and decreased expression of claudin 1 (-6.7-fold) and claudin 3 (-3.6-fold). LPS was found to be a potent inducer of small bile duct injury following hepatic ischemia and 6 hours of reperfusion. This injury was associated with increased permeability of the BBB and impaired hepatic bile salt clearance. Liver Transplantation 23 194-206 2017 AASLD.

Neither Isolated Hepatic Arterial Clamping nor Hepatic Arterial Ligation Induce Ischemic Type Biliary Lesions in Rats.

BACKGROUND Ischemic type biliary lesions (ITBL) is a troublesome complication after liver transplantation. Little is known about its pathogenesis and there is particularly little data about morphological alterations. Prolonged warm and cold ischemia time and reduced hepatic arterial perfusion are risk factors leading to ITBL. There are only a few animal models described in literature. Therefore, we examined the effects of 3 h of hepatic artery ischemia-reperfusion (3 h I/R) and hepatic arterial ligation (HAL), both combined with ligation of the peribiliary plexus (PBP). MATERIAL AND METHODS 3 h I/R was performed by clamping the hepatic artery with microvascular clamps for 3 h. HAL was performed by ligation of the hepatic artery. Both procedures were combined with stenting of the common bile duct with double ligation of the PBP. A sham group without clamping served as control. Serum activities of aspartate transaminase (AST) and alanine transaminase (ALT), direct and total bilirubin (DB/TB), and lactate dehydrogenase (LDH) were measured. Bile flow was analyzed and histological examinations of leukocyte infiltration (CAE), cell proliferation (PCNA), apoptotic cells (HE), and bile ducts morphology (CK7) were performed. Western blots of the vascular endothelial growth factor (VEGF) and caspase 3 were made to investigate vascular growth expression and apoptotic cell death. RESULTS 3 h I/R and HAL were associated with a significant hepatocellular injury and inflammation, shown through increased AST and ALT, leukocyte infiltration, and apoptotic cell death. An increase of bile ducts and a reduction of arteries/bile duct ratio after 30 days was observed in the 3 h I/R group and HAL, but no ITBL-typical bile duct necrosis, intrahepatic strictures, or dilatations of bile ducts occurred. CONCLUSIONS Morphological alterations in a rat animal model of 3 h I/R and HAL could be demonstrated. However, a model of intrahepatic biliary lesions could not be established through hepatic arterial ligation or through 3-h hepatic arterial ischemia and reperfusion.

Arterial blood gas anomaly in canine hepatobiliary disease.

Arterial blood gas analysis is an important diagnostic and monitoring tool for respiratory abnormalities. In human medicine, lung complications often occur as a result of liver disease. Although pulmonary complications of liver disease have not been reported in dogs, we have frequently encountered hypoxemia in dogs with liver disorders, especially extrahepatic biliary obstruction. In addition, respiratory disorders account for 20% of perioperative fatalities in dogs. Therefore, in this study, we evaluated the respiratory status in dogs with hepatobiliary disease by arterial blood gas analysis. PaO2 and PaCO2 were measured. Alveolar-arterial oxygen difference (AaDO2), the indicator of gas exchange efficiency, was calculated. Compared to healthy dogs (control group), hepatobiliary disease dogs had significantly lower PaO2 and higher AaDO2. Hypoxemia (PaO2 of ≤80 mmHg) was observed in 28/71 dogs with hepatobiliary disease. AaDO2 was higher (≥30 mmHg) than the control group range (11.6 to 26.4 mmHg) in 32/71 hepatobiliary disease dogs. By classifying type of hepatobiliary disease, dogs with extrahepatic biliary obstruction and chronic hepatitis showed significantly lower PaO2 and higher AaDO2 than in a control group. Dogs with chronic hepatitis also had significantly lower PaCO2. The present study shows that dogs with hepatobiliary disease have respiratory abnormalities more than healthy dogs. Preanesthetic or routine arterial blood gas analysis is likely beneficial to detect the respiratory abnormalities in dogs with hepatobiliary disease, especially extrahepatic biliary obstruction and chronic hepatitis.

Serum alkaline phosphatase and bilirubin are early surrogate markers for ischemic cholangiopathy and graft failure in liver transplantation from donation after circulatory death.

Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure.