The inv mouse as an experimental model of biliary atresia

Background/Purpose

The causation of biliary atresia (BA) remains unclear. However, ductal plate malformation (DPM), maldevelopment of the intrahepatic bile ducts, is 1 of the preferred theories. The inv homozygous mouse (inv mouse), created by insertional mutagenesis, shows situs inversus and jaundice. This study investigated whether the inv mouse could be an experimental model of human BA.

Methods

In the inv mice (n = 12) and wild-type littermates (n = 12), we examined the liver function and morphologic changes in the biliary tract through serum biochemical study and morphological study.

Results

The level of serum total and conjugated bilirubin in the inv mouse was 8.1 ± 3.8 and 4.4 ± 2.4 mg/dL, respectively, significantly higher than in the wild type. Macroscopically, 11 (92%) of 12 inv mice had situs inversus, and 3 (25%) of 12 mice had preduodenal portal vein. Histologically, the continuity of the extrahepatic bile duct was preserved. However, DPM, showing proliferative biliary epithelium around the intrahepatic portal vein, was found in the liver of the inv mouse.

Conclusion

In the inv mouse, the pathologic changes in DPM were found in the intrahepatic biliary system, which were observed in some clinical cases of BA. Therefore, the intrahepatic biliary system of the inv mouse could be an experimental model of human BA with DPM.     

An experimental study of selective intrahepatic biliary ablation with ethanol

BACKGROUND: Few attempts have been made to investigate the feasibility of selective intrahepatic biliary ablation with absolute ethanol. METHODS: Through a catheter cannulated into the bile duct of the left lateral and median lobes (70% of total liver weight), 0.2 mL of absolute ethanol was injected into rats. RESULTS: The weight of the infused lobes decreased to less than 50% of the entire liver weight 14 days after treatment, while the weight of the noninfused lobes increased to 1.6-fold of the original value. This increase was associated with a markedly elevated Ki-67 labeling index. Both bile flow and bile acid excretion in the noninfused lobes significantly increased to more than twice the original values on Day 14. Histologically, the interlobular bile ducts of the infused lobes were destroyed. Ethanol also soaked through Glisson's capsule and destroyed hepatocytes, which were replaced by fibrous tissue and proliferating bile ductules without necrosis by Day 14. The portal veins and hepatic arteries supplying the infused lobes were structurally well preserved throughout the study period. CONCLUSION: Selective biliary infusion of ethanol can be performed safely without serious complications, achieving lobar ablation with contralateral hypertrophy of the liver.     

Intrahepatic biliary atresia in Down's syndrome.

A case of intrahepatic atresia in Down's syndrome is presented. It seems likely that atresia of intrahepatic bile ducts in Down's syndrome is due to a chromosomal disorder.     

Intrahepatic mast cell population correlates with clinical outcome in biliary atresia

PURPOSE: To determine if mast cells influence the clinical outcome in biliary atresia (BA), the authors examined the intrahepatic mast cell population in BA. METHODS: Mast cells were identified histochemically using Toludin Blue and immunohistochemically using antimast cell tryptase antibody in formalin-fixed paraffin-embedded sections from 21 cases of BA. Patients were divided into 3 groups; group I (n = 8) with good liver function, group II (n = 8) with moderate liver dysfunction, and group III (n = 5) with severe liver dysfunction. Liver biopsies from patients with choledochal cysts (CDC, n = 5), and normal liver (NL, n = 4) served as controls. The results were compared among the groups. RESULTS: Both histochemical and immunohistochemical methods showed similar data. Mast cells were seen mostly in the portal tracts. Mast cell numbers per medium power field (20 x magnification) were higher in BA than in the controls (15. 03 +/- 2.25 v 3.85 +/-.65, [mean +/- SEM], P <.05, BA v CDC; 15.03 +/- 2.25 v 1.73 +/-.06, [mean +/- SEM], P <.05, BA v NL, immunohistochemical data). Clinical correlation showed an association between higher mast cell number and liver dysfunction (32.62 +/-.80 v 8.52 +/-.87 [mean +/- SEM], group III v group I; P <. 05, immunohistochemical data). CONCLUSION: Increased mast cell population in BA adversely affects liver function and raises the possibility that type I allergic reaction may play role in the pathology of BA.     

Intrahepatic biliary cysts in children with biliary atresia who have had a Kasai operation

Purpose

In patients with biliary atresia who had undergone a Kasai operation, treatment of intrahepatic biliary cysts (IBCs), particularly when complicated by cholangitis, is often difficult because the clinical implications and the course of IBCs are unclear. Thus, to determine the best treatment guideline, the morphology of IBCs, the clinical course, and the outcomes of such patients were evaluated.

Patients and Methods

A total of 44 patients with type III biliary atresia who underwent a Kasai operation from 1977 to 2005 were postoperatively examined for IBC by using ultrasonography and computed tomography. We classified the IBCs based on their number and shape.

Results

Intrahepatic biliary cysts developed in 12 of 54 patients. Three patients with solitary simple cysts and 1 patient with multiple simple cysts had no history of cholangitis. Two patients with multiple simple cysts had cholangitis at the time of IBC diagnosis and were treated with percutaneous transhepatic cholangiodrainage (PTCD). Patients with simple IBCs did not develop persistent cholangitis and their prognosis depended largely on their liver function; 3 of 6 patients remained healthy without cholangitis, whereas 3 patients required liver transplantation (LT) because of progressive liver failure or worsening hepatopulmonary syndrome, and not severe cholangitis. On the other hand, all 6 patients with multiple complicated IBCs had persistent cholangitis, eventually requiring LT. Even after bile flow to the intestine was reestablished after PTCD, both IBCs and cholangitis recurred. These patients required LT because of severe cholangitis.

Conclusions

Intrahepatic biliary cysts without cholangitis are not a source of infection and require no treatment. Simple IBCs with cholangitis can be controlled by antibiotics and/or PTCD. Patients with multiple complicated IBCs have a poor prognosis, requiring LT to control cholangitis. Although PTCD can control cholangitis in these patients as they wait for LT, PTCD does not alleviate it—LT is the final solution.     

Intrahepatic cystic lesions in children with biliary atresia after Kasai procedure

BackgroundIntrahepatic cystic lesion (ICL) is a common complication for biliary atresia post-Kasai portoenterostomy. The purpose of this study was to review the cases in our hospital and assess the correlation between characteristics of ICL and clinical outcomes.MethodsWe retrospectively analyzed 787 cases of biliary atresia from 2012 to 2016. Demographics, clinical details, and postoperative outcomes were reviewed.ResultsA total of 76 patients were diagnosed with ICLs using ultrasound post-Kasai procedure, and the incidence was 9.7%. Preoperative characteristics showed no significant differences between ICL (+) and ICL (?) groups. Nearly 70% (53/76) of the patients with ICLs had a history of cholangitis. The 2-year native liver survival rate was 60.4% for those with a history of cholangitis and 87% for those without (P = 0.017). Further analysis showed that the 2-year native liver survival rate was 42.9% for those diagnosed within 3 months post-Kasai procedure, 54.2% for those diagnosed between 3 and 6 months, and 80.0% for those diagnosed beyond 6 months (P = 0.002), while no significance was observed for type (P = 0.094) or site (P = 0.406) of ICL.ConclusionPatients with ICLs had a high incidence of cholangitis. The prognosis was closely related with the history of cholangitis and the onset time of ICLs.Level of evidenceLevel II.     

Cholangiocyte secretion of chemokines in experimental biliary atresia

Biliary atresia (BA) is a disease of the newborn that results in obstruction of the biliary tree. The cause of BA remains unknown; however, recent studies using the murine model of biliary atresia have found that rotavirus infection of the biliary epithelial cell (cholangiocyte) triggers an inflammatory response. We hypothesized that rotavirus infection of cholangiocytes results in the release of chemokines, important mediators of the host immune response.

Methods

In vivo, Balb/c pups were injected with rhesus rotavirus (RRV) or saline, and, their extrahepatic bile ducts were microdissected 2, 5, 7, and 14 days after injection. Next, an immortalized cholangiocyte cell line (mCl) was incubated with RRV or serum-free media. Qualitative and quantitative chemokine assessment was performed using enzyme-linked immunosorbent assay, polymerase chain reaction, and immunohistochemistry.

Results

In vivo, increased levels of the chemokines macrophage inflammatory protein 2, monocyte chemotactic protein 1, KC and Regulated upon Activation, Normal T Expressed and Secreted were found in RRV-infected murine bile ducts. In vitro, infected mCl cells produced increasing amounts of these same chemokines in relation to dose and time.

Conclusion

These novel results suggest that chemokine expression by RRV-infected cholangiocytes may trigger a host inflammatory process that causes bile duct obstruction. Understanding how viral infection initiates this response may shed light on the pathogenesis of biliary atresia.     

Combined pure esophageal atresia, duodenal atresia, biliary atresia, and pancreatic ductal atresia: prenatal diagnostic features and review of the literature

The authors recently managed a case of combined pure esophageal, duodenal, biliary, and pancreatic ductal atresia in a fetus and newborn with Trisomy 21. The authors present a case report and review of the literature, emphasizing the prenatal radiographic features of the combined lesions and the high incidence of associated anomalies including Down's syndrome. Prenatal suspicion of these anomalies warrants karyotype analysis as well as careful pre- and postnatal screening for other anomalies.     

Cystic biliary atresia: an etiologic and prognostic subgroup

Introduction

Cystic biliary atresia (CBA) is an uncommon variant of biliary atresia (BA) in which prognosis may be relatively favorable but liable to misdiagnosis as choledochal cyst, and potentially offers insights into the etiology of BA. Because some cases can be detected antenatally, CBA in general may have its origins in utero life. We assessed our experience with CBA.

Methods

Single-center retrospective review of infants with CBA over a 13-year period (January 1994 to December 2006) was done. Data are given as medians (range).

Results

Of 270 infants with BA, 29 (9 male) were identified as CBA. Antenatal ultrasonography had detected an abnormality in 12 (41%) infants at a median of 22 weeks (17-34 weeks) of gestation. All infants underwent postnatal excision and Kasai portoenterostomy (KP). Those with antenatally detected CBA came to surgery younger (36 [14-67] vs 48 days [35-147 days], P = .004). Twenty cysts (69%) had a fibroinflammatory wall with no biliary epithelial lining and 6 (26%) contained bile. Age at KP was significantly and positively correlated (r = 0.46, P = .01) with liver fibrosis, as assessed in liver biopsy materials obtained at KP, but not with grade of “hepatocyte disarray” (P = .74). Twenty infants (69%) cleared their jaundice (bilirubin <20 μmol/L) within 6 months after KP. Age at KP markedly affected outcome.

Conclusion

Cystic BA is a clinically distinct variant of BA. Despite onset in prenatal life, earlier than presumed for isolated BA, it has a better prognosis, particularly with early surgery.     

Successful revision of portoenterostomy in an infant with biliary atresia

We present a case report of a boy with biliary atresia who, after hepatoportoenterostomy performed on day 21 of life, had immediate resolution of cholestasis and remained anicteric until 3.5 months of age. He then abruptly developed acholic stools. Nuclear medicine imaging study showed no excretion. Broad-spectrum antibiotics and corticosteroids were administered but did not lead to clinical improvement; a surgical revision of the original anastomosis was undertaken at 4 months of age. At 14 months of age, the child is anicteric and growing well. In this case, successful revision of hepatoportoenterostomy averted the need for liver transplantation.     

Stoma-related variceal bleeding: an under-recognized complication of biliary atresia

The medical records of 52 children with biliary atresia treated by portoenterostomy and evaluated for liver transplantation were reviewed to determine the frequency of stoma variceal bleeding and the optimal strategies for prevention and treatment. Eighteen patients had had prior stoma closure, four by preperitoneal closure without takedown from the abdominal wall. Three of the four developed occult variceal bleeding from the stoma closure site. Twenty-two patients had a stoma present at evaluation. All 22 patients with stomas (100%) had at least one bleeding episode requiring transfusion. Treatment included transfusion and local pressure (9), suture ligation of the bleeding site (5), and stoma closure and/or takedown (11). Local treatment led to recurrences in eight of 14 (57%) of the cases. To reduce the high mortality in patients with biliary atresia awaiting liver transplantation, multiple variceal bleeding episodes should be prevented. To eliminate one source, stoma variceal bleeding, the stoma, whether functioning or nonfunctioning should be taken down and closed. Preperitoneal closure alone does not prevent stoma bleeding.     

Intrahepatic biliary cystadenoma presenting with obstructive jaundice

Biliary cystadenoma (BCA) is a rare neoplasm of the bile duct with malignant potential. We report a case of intrahepatic BCA with an unusual presentation of obstructive jaundice. Computed tomography scan of the abdomen revealed a dilated common bile duct and intrahepatic ducts with internal septa. Endoscopic retrograde cholangiography showed an oval filling defect in the bile duct causing the obstruction. At laparotomy, this proved to be a multiloculated mucinous polyp in the common bile duct, with its origin in the left intrahepatic duct, detected using intraoperative choledochoscopy. A left hemihepatectomy was performed, and histology confirmed intrahepatic mucinous BCA with mesenchymal stroma. The imaging process and surgical options for BCA are discussed.     

Multiple intrahepatic biliary cysts in children with biliary atresia

Purpose: The aim of this study was to investigate the incidence, clinical course, and outcome of multiple intrahepatic biliary cysts in patients with biliary atresia. Methods: From 1992 to 2000, 154 patients with biliary atresia were examined for intrahepatic cysts. They were followed and examined routinely using abdominal ultrasonography. Results: Twenty-three patients had single intrahepatic cysts, and 16 patients had multiple cysts. The incidence of intrahepatic cysts in these patients were 25.3% (39 of 154) for all kinds of cysts and 10.4% (16 of 154) for multiple intrahepatic cysts. Of the 16 patients with multiple cysts, 13 (81.3%) had jaundice, and 15 (93.8%) had a history of cholangitis before cysts were detected. Image studies showed multiple discrete ovoid or round intrahepatic biliary cysts with various sizes along the biliary trees. The cysts decreased in size or number in 7 patients after antibiotic treatment and disappeared in only one patient. The mortality rate was higher in patients with multiple cysts than in those with single cysts (P = .037). Conclusions: Multiple intrahepatic biliary cysts are a common complication in patients with biliary atresia and suggests a poor prognosis. Prolonged parenteral antibiotics treatment should be administered when signs of biliary infection appear. J Pediatr Surg 37:1183-1187.     

Reoperation in patients with biliary atresia

Twenty-seven reoperations were done on 23 patients among 100 infants with biliary atresia who have been treated at Tohoku University Hospital between 1971 and 1981. Nineteen patients had a single reoperation and 4 patients had 2 reoperations. We present the results and the role of reoperation in biliary atresia patients in our institution. Excellent bile drainage after reoperation was obtained in 13 of 15 patients with good bile flow after the initial operation. On the contrary, good bile drainage was not obtained by reoperation in 8 of 12 cases without active bile flow after the initial operation. Cessation of bile flow after successful initial operation is an absolute indication for reoperation. Aggressive reoperations under proper indications improve the surgical results in biliary atresia patients.     

Intrahepatic biliary papillomatosis: a case report

The Authors describe a case of intrahepatic biliary papillomatosis, which extended from the left to part of the right hepatic biliary tract. Biliary papillomatosis is a rare disease characterised by obstruction and frequently by cholangitis. The diagnosis is possible only after the final pathological analysis. The patient was studied with MRI cholangiography, which showed amorphous material in the biliary tract. The surgical treatment was a left hepatectomy (primary therapy) and an intensive follow-up was recommended. Biliary papillomatosis may become a new indication for liver transplantation.     

Intrahepatic biliary lithiasis: endoscopic transpapillary treatment

Six cases of intrahepatic biliary lithiasis, condition rarely observed in western countries, are reported. Following a review of the literature and on the basis of personal experience, stress is laid on problems of classification, clinical and instrumental diagnosis and, in particular, the therapeutic approach to intrahepatic biliary lithiasis by the endoscopic transpapillary way.     

肝内胆管囊腺瘤一例

腺瘤的管腔中有分泌物潴留呈囊状扩张者称为囊腺瘤.由于被覆内壁的腺上皮细胞的增殖,形成多数大小不一的房室,内容物可有浆液、黏液、假黏液、胶质等多种物质.囊腺瘤以卵巢最为多见,此外也见于乳腺、肾脏、胰腺,发生于肝脏的囊腺瘤较少见.现就我院肝胆外科收治的1例肝内胆管囊腺瘤(intrahepatic biliary cysta...     

Rotavirus particles in the extrahepatic bile duct in experimental biliary atresia

Background

Biliary atresia (BA) is the most common indication for liver transplantation in children. The experimental model of BA, induced by rotavirus infection in neonatal mice, has been widely used to investigate the inflammatory aspects of this disease. We investigated the kinetics and the localization of the viral infection in this murine model.

Methods

In this study 399 animals were employed for a detailed investigation of rhesus rotavirus (RRV)-induced BA. RRV kinetics was analyzed by rtPCR and its (sub) cellular localization investigated using whole mounts which were further processed for confocal and electron microscopy.

Results

The BA mouse model resulted in up to 100% induction of atresia following RRV injection. The kinetics of RRV infection differed between liver and extrahepatic bile ducts. While the virus peak up to day 10 postinfection was similar in both organs, the virus remained detectable in extrahepatic bile duct cells up to day 21. Interestingly, RRV particles were localized not only in cholangiocytes but also in cells of the subepithelial layers, potentially macrophages.

Conclusions

RRV remains present in the extrahepatic bile duct cells after an initial virus peak. Viral particles were detected in subepithelial cells in contrast to the described tropism toward cholangiocytes.