Management of paediatric liver trauma.

Of all the intra-abdominal solid organs, the liver is the most vulnerable to blunt abdominal trauma. The majority of liver ruptures present in combination with other abdominal or extra-abdominal injuries. Over the last three decades, the management of blunt liver trauma has evolved from obligatory operative to non-operative management in over 90% of cases. Penetrating liver injuries more often require operative intervention and are managed according to adult protocols. The greatest clinical challenge remains the timely identification of the severely damaged liver with immediate and aggressive resuscitation and expedition to laparotomy. The operative management can be taxing and should ideally be performed in a dedicated paediatric surgical centre with experience in dealing with such trauma. Complications can occur early or late and include haemobilia, intrahepatic duct rupture with persistent biliary fistula, bilaemia, intrahepatic haematoma, post-traumatic cysts, vascular outflow obstruction, and gallstones. The prognosis is generally excellent.

Choleperitoneum due to intrahepatic bile duct rupture - case report.

Non-traumatic perforations of the bile ducts are unfrequently encountered entities, all the more when they affect the intrahepatic bile ducts, exteriorizing their biliary content in the great peritoneal cavity. Reporting such a case has determined the authors to perform a careful overview of the cases present in the literature. An observation that can be made based on these is that the obstruction of the main bile duct due to lithiasis determines, by pressure increase, the dilation of the bile system branches, all on the background of an unknown malformation of the intrahepatic bile ducts.

PERCUTANEOUS CHOLANGIOSCOPY AND LASER BILIARY LITHOTRIPSY FOR BILIARY INTRAHEPATIC STONES MANAGEMENT: CASE REPORT.

Intrahepatic biliary stone disease is a difficult condition to treat, due to anatomical complexity of biliary tract, association with colestasis, and high recurrence rates, with potential short- and long-term complications, such as cholangitis and secondary biliary cirrhosis. Removal of biliary stones via intraductal access can be achieved endoscopically or percutaneously, with preference for cholangioscopy-guided laser lithotripsy in complex cases. The surgical approach, despite its prolonged results, is a more invasive and risky procedure. The authors present a case of cholangioscopy with percutaneous laser biliary lithotripsy as an option for the treatment of intrahepatic biliary stone disease associated with biliary stricture following biliodigestive anastomosis due to bile duct injury following cholecystectomy, a safe and effective alternative with low morbidity and satisfactory outcomes in follow-up.

Notch signaling regulates tubular morphogenesis during repair from biliary damage in mice.

BACKGROUND & AIMS: Repair from biliary damages requires the biliary specification of hepatic progenitor cells and the remodeling of ductular reactive structures into branching biliary tubules. We hypothesized that the morphogenetic role of Notch signaling is maintained during the repair process and have addressed this hypothesis using pharmacologic and genetic models of defective Notch signaling. METHODS: Treatment with DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) or ANIT (alpha-naphthyl-isothiocyanate) was used to induce biliary damage in wild type mice and in mice with a liver specific defect in the Notch-2 receptor (Notch-2-cKO) or in RPB-Jk. Hepatic progenitor cells, ductular reaction, and mature ductules were quantified using K19 and SOX-9. RESULTS: In DDC treated wild type mice, pharmacologic Notch inhibition with dibenzazepine decreased the number of both ductular reaction and hepatic progenitor cells. Notch-2-cKO mice treated with DDC or ANIT accumulated hepatic progenitor cells that failed to progress into mature ducts. In RBP-Jk-cKO mice, mature ducts and hepatic progenitor cells were both significantly reduced with respect to similarly treated wild type mice. The mouse progenitor cell line BMOL cultured on matrigel, formed a tubular network allowing the study of tubule formation in vitro; γ-secretase inhibitor treatment and siRNAs silencing of Notch-1, Notch-2 or Jagged-1 significantly reduced both the length and number of tubular branches. CONCLUSIONS: These data demonstrate that Notch signaling plays an essential role in biliary repair. Lack of Notch-2 prevents biliary tubule formation, both in vivo and in vitro. Lack of RBP-Jk inhibits the generation of biliary-committed precursors and tubule formation.

Intrahepatic biliary ablation with pure ethanol: an experimental model of biliary atresia.

PURPOSE: We describe a new rat model of biliary atresia, induced by biliary ablation with pure ethanol. METHODS: A catheter was inserted and fixed in the common bile duct of male rats. Saline or pure ethanol was injected through the catheter and the animals were monitored for 8 weeks thereafter. We measured total bilirubin (T-Bil), aspartate aminotransferase (AST), alanine transaminase (ALT), and hyaluronic acid (HA) and examined liver biopsy specimens immunohistochemically for α-smooth muscle actin staining (α-SMA) and transforming growth factor-ß1 (TGF-ß1). RESULTS: The ethanol injection group animals were further divided into a temporary and a persistent liver dysfunction group. In the persistent group, T-Bil, AST, ALT and HA levels were significantly higher after 8 weeks in the persistent group than in the control group and the temporary group. In the ethanol injection group, α-SMA expression was prominent in the surrounding proliferative bile ducts and portal areas. The distribution of TGF-ß1 was found prominently in hepatocytes in the center of nodules and in ductular epithelial cells. CONCLUSIONS: This study characterizes the effects of ethanol-induced bile duct injury in rats, resulting in sclerosing cholangitis and its secondary effects. We believe that this experimental model will prove useful in the study of biliary atresia.

Liver resection in management of post-cholecystectomy biliary injury: a case series.

BACKGROUND/AIMS: Management of post-cholecystectomy bile duct injuries may, in certain cases, require hepatectomy. In the literature, indications for hepatectomy in this setting are not clear. METHODOLOGY: A retrospective review of our database for patients referred for post-cholecystectomy bile duct injuries from January 2003 to January 2008 was performed. RESULTS: We present three cases of hepatectomy among 45 patients (6.7%) referred for post-cholecystectomy bile duct injuries. Two of these patients had been referred after one or more previous attempts at operative repair in an outside hospital. In one patient, the decision to perform hepatectomy was based on the proximal pattern of biliary stricture aggravated by disruption of the right hepatic artery, leading to irreversible secondary sclerosing cholangitis. Biliary stricture also involved bifurcation and was complicated by liver atrophy in the 2 other patients. Despite complication(s) in 2 out of 3 patients, the long-term outcome was good in all cases. CONCLUSIONS: In our experience, the indication for hepatectomy in post-cholecystectomy bile duct injuries, combined with vascular injuries and liver atrophy in symptomatic patients.

Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans.

Epithelial-mesenchymal transitions (EMTs) play an important role in tissue construction during embryogenesis, and evidence suggests that this process may also help to remodel some adult tissues after injury. Activation of the hedgehog (Hh) signaling pathway regulates EMT during development. This pathway is also induced by chronic biliary injury, a condition in which EMT has been suggested to have a role. We evaluated the hypothesis that Hh signaling promotes EMT in adult bile ductular cells (cholangiocytes). In liver sections from patients with chronic biliary injury and in primary cholangiocytes isolated from rats that had undergone bile duct ligation (BDL), an experimental model of biliary fibrosis, EMT was localized to cholangiocytes with Hh pathway activity. Relief of ductal obstruction in BDL rats reduced Hh pathway activity, EMT, and biliary fibrosis. In mouse cholangiocytes, coculture with myofibroblastic hepatic stellate cells, a source of soluble Hh ligands, promoted EMT and cell migration. Addition of Hh-neutralizing antibodies to cocultures blocked these effects. Finally, we found that EMT responses to BDL were enhanced in patched-deficient mice, which display excessive activation of the Hh pathway. Together, these data suggest that activation of Hh signaling promotes EMT and contributes to the evolution of biliary fibrosis during chronic cholestasis.

Intrahepatic bile duct dilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma: impact on patient's prognosis.

BACKGROUND: Percutaneous radiofrequency ablation (RFA) has been widely accepted as an alternative to surgery for small hepatocellular carcinoma (HCC). In RFA, a portion of liver tissue surrounding tumour is also ablated to achieve a safety margin. The intrahepatic bile duct may be injured and result in chronic bile duct dilatation upstream of the injured site. However, the impact of such an injury on the overall prognosis has been unclear. METHODS: Patients who showed bile duct dilatation following RFA were identified by a retrospective review of imaging studies. Each dilatation was classified as mild (limited to one hepatic subsegment) or severe (affecting two or more subsegments). The relation between the incidence of intrahepatic bile duct dilatation and HCC recurrence or survival was analysed using proportional hazard models. RESULTS: Among 589 consecutive HCC patients treated with RFA, 70 (11.9%) and 21 (3.6%) patients showed mild and severe bile duct dilatation respectively. Patients with severe dilatation, but not those with mild dilatation, had lower survival and higher HCC recurrence than patients without dilatation. Severe dilatation, but not mild dilatation, was significantly associated with death [hazard ratio (HR) 2.17, P=0.035] and recurrence (HR 2.89, P<0.001). CONCLUSION: Whereas mild bile duct dilatation after RFA is clinically negligible, bile duct dilatation affecting two or more subsegments should be regarded as a complication that may affect the prognosis and should be observed carefully.

Early vs. delayed repair of isolated segmental, sectoral and right hepatic bile duct injuries.

BACKGROUND/AIMS: To compare the outcome of early (within the first 2 weeks) and delayed (between 2 weeks and 24weeks) repair of segmental, sectoral and right hepatic bile duct injuries (SSRBDI). METHODOLOGY: Data on all patients with SSRBDI were collected prospectively. In the absence of infection, biliary peritonitis or biliary fistula, repair was considered within 2 weeks. RESULTS: Between June 1984 and June 2009, 282 patients were referred with injury to the bile tree. Of these 282 patients, 51 were segmental, sectoral and right hepatic bile duct injuries (SSRBDI). Repair of the SSRBDI injury had been attempted in 8 patients before referral. Of the 43 patients with no previous repair, two were managed without surgery and 41 required subsequent surgical reconstruction of the ductal injury. Within the first 2 weeks after injury, 19 patients underwent early biliary repair. Between 2 weeks and 24 weeks, 22 patients underwent delayed repair. Successful repair was possible in 18 of 19 early repairs compared with 20 of 22 delayed repairs (p=0.669). CONCLUSIONS: Early repair within the first 2 weeks achieved a similar result to that of delayed repair when repair of SSRBDI was undertaken in unit experienced in the management of biliary injury.

Ultrasound identification of traumatic pneumobilia.

A 65-year-old woman presented to the emergency department with low back pain after being hit by a truck at low speed. Although her abdominal examination showed benign results, an extended Focused Assessment With Sonography in Trauma ultrasound examination was performed and incidentally demonstrated evidence of pneumobilia. There were no additional intra-abdominal injuries noted. Subsequent computed tomography and magnetic resonance cholangiopancreatography confirmed these findings. The etiology of traumatic pneumobilia is discussed with a brief review of the literature on the subject.

Partial segment-IV/V liver resection facilitates the repair of complicated bile duct injury.

The ability to perform a technically perfect anastomosis remains the key to success in bile duct repair. This report describes our technique in facilitating the performance of a good surgical anastomosis for difficult bile duct repair. In the present study are presented 3 cases of bile duct repair for a Strasberg type-E3 stricture, a Strasberg type-E4 fistula and an anastomotic stricture of a previously performed choledochojejunostomy for the correction of bile duct injury. The approach was to perform partial resection of the lower part of segments IV and V. The hepatoduodenal ligament was not dissected. The anterior surface of the bile duct was utilized to perform Roux-en-Y hepaticojejunostomy. Operative times ranged from 4 to 5 hours, and Pringle times 15 to 25 minutes. There was no vascular injury. We were able to perform wide anastomoses, facilitated by excellent exposure of the hilar plate. There was no any complication. Partial resection of the hepatic segments IV-V provides excellent exposure of the hilar plate. The risk of vascular injury was minimized by avoiding dissection of the hepatoduodenal ligament. It is believe this technique may offer a superior approach to difficult repair of complicated bile duct injury.

Mechanical strength of biliary defect closure after topical sealing: Comparison of four sealants in a porcine model.

BACKGROUND/OBJECTIVE: Biliary leakage is a potential complication of liver resection and is still a concern. The aim of the present study was to evaluate the effectiveness of four routinely used sealants in preventing bile leakage under pressure from an induced perforation of the gallbladder in a porcine model. METHODS: Forty Landrace pigs were randomly assigned to one of five groups. These included a control group (n = 8) and one group each for the sealants TachoSil®, TissuCol Duo®, Coseal®, and FloSeal® (n = 8 per group). In the control group, the perforation was left unsealed. To evaluate the biliostatic potential of the sealants, we measured the pressure that was needed to induce leakage (mmHg) and the gallbladder volume (cc) at the time of leakage in each group. RESULTS: A significantly higher mean pressure was required to induce leakage in the sealant groups compared with the control group. However, the biliostatic effects were heterogeneous among the sealant groups. Sealants with the highest to lowest effectiveness were TachoSil, Coseal, TissuCol, and FloSeal. The mean gallbladder volume at the time of leakage also varied between sealant groups. CONCLUSION: Biliostatic properties are markedly improved by the use of modern sealants compared with using no sealant. However, the advantages and disadvantages of using sealants should be carefully considered in each clinical situation. The effectiveness of the sealants should be evaluated in chronic and clinical studies.

The role of bile salt toxicity in the pathogenesis of bile duct injury after non-heart-beating porcine liver transplantation.

BACKGROUND: Intrahepatic bile duct strictures are a serious complication after non-heart-beating (NHB) liver transplantation. Bile salt toxicity has been identified as an important factor in the pathogenesis of bile duct injury and cholangiopathies. The role of bile salt toxicity in the development of biliary strictures after NHB liver transplantation is unclear. METHODS: In a porcine model of NHB liver transplantation, we studied the effect of different periods of warm ischemia in the donor on bile composition and subsequent bile duct injury after transplantation. After induction of cardiac arrest in the donor, liver procurement was delayed for 0 min (group A), 15 min (group B), or more or equal to 30 min (group C). Livers were subsequently transplanted after 4 hr of cold preservation. In the recipients, bile flow was measured, and bile samples were collected daily to determine the bile salt-to-phospholipid ratio. Severity of bile duct injury was semiquantified by using a histologic grading scale. RESULTS: Posttransplantation survival was directly related to the duration of warm ischemia in the donor. The bile salt-to-phospholipid ratio in bile produced early after transplantation was significantly higher in group C, compared with group A and B. Histopathologic condition showed the highest degree of bile duct injury in group C. CONCLUSION: Prolonged warm ischemia in NHB donors is associated with the formation of toxic bile after transplantation, with a high biliary bile salt-to-phospholipid ratio. These data suggest that bile salt toxicity contributes to the pathogenesis of bile duct injury after NHB liver transplantation.