Ultrasonographic findings and management of intrahepatic biliary tract abnormalities after portoenterostomy

Ultrasonographic examinations was made in 24 children who had undergone a portenterostomy to correct extrahepatic biliary atresia. Abnormalities were observed in six patients. These were the result of ongoing inflammatory reactions because all had been suffering from cholangitis after surgery, and the size of the biliary tract structure changed in accordance with the occurrence and subsidence of the cholangitis. Ultrasonographic examination showed dilation of the intrahepatic bile duct in one patient and cystic lesions in five patients. Treatment included percutaneous transhepatic bile drainage for dilated bile ducts, alcohol injections for intrahepatic cysts, and reoperation for cysts in the porta hepatis. Treatment was not required for cysts in controllable cholangitis. The results of these approaches were excellent, indicating that they were of benefit in treatment intrahepatic abnormalities occurring after portoenterostomy.     

Extrahepatic biliary atresia: a review of current management

Macroscopic examination of the extrahepatic bile ducts in infants with biliary atresia reveals fibrous occlusion of variable extent from an inflammatory process of unknown aetiology. Histological studies have shown that bile duct remnants at the porta hepatis frequently contain small epithelium-lined channels which communicate with intrahepatic ducts and through which effective bile drainage may be established by the operation of portoenterostomy. The 4-year survival rate in untreated cases is 2 per cent, but surgical treatment can improve the outlook and recent reports suggest that a 5-year survival rate of over 35 per cent can be achieved with portoenterostomies performed before 10 weeks of age. Complications after surgery include progressive liver disease, ascending bacterial cholangitis and portal hypertension.     

A histopathological study of the remnant of extrahepatic bile duct in so-called uncorrectable biliary atresia

Histopathological study of the remnant of extrahepatic bile ducts in 40 cases of so-called uncorrectable biliary atresia, upon which we operated the last three years, has been performed. The histological findings of the remnant were classified into three types.Only two cases were found to have type 1a ducts in the porta hepatis area, from which we can expect better prognosis postoperatively. We also found that as the patients become older, the size of the duct in the remnant becomes smaller and the hepatic fibrosis becomes more remarkable. Therefore the operation should be performed in the infant with this lesion as young as possible.As for the evaluation of operative results of hepatic portoenterostomy for this lesion, a proper evaluation can be made only in those cases in which a microscopic examination of the remnant of extrahepatic bile duct at the porta hepatis area has been adequately performed.Concerning the pathogenesis of biliary atresia, we presume that congenital abnormalities of bile ducts are a basic factor, and additional nonspecific inflammation and bile stasis complete its pathological condition.     

The surgery of "correctable" biliary atresia

Seven of 114 (6%) patients treated in Denver for biliary atresia had a variant of the disease in which only microscopic bile ducts or ductules were identified at the porta hepatis, hepatic lesions were present, even in the neonatal example, and intrahepatic biliary hypoplasia was uniformly present. The excised bile duct cysts consisted of fibrosis or scar tissue and with little or no epithelial lining. Six patients had corrective surgery. The first patient was treated by choledochoenterostomy and became totally obstructed. Definitive operation in this patient and all subsequent patients consisted of excision of all extrahepatic duct structures and Roux-en-Y portoenterostomy. Two patients died, the one who did not have surgical correction and a second who had correction at age 35 weeks. The other five patients have been followed for 18 to 158 months and are anicteric but have some degree of residual liver damage. We conclude that so-called correctable biliary atresia occurs in less than 10% of cases, that because of coincident biliary hypoplasia, "cure" is not a possible outcome, and that the treatment of choice is complete surgical excision of the extrahepatic bile ducts and Roux-en-Y portoenterostomy.     

Histopathologic study of the extrahepatic biliary system in uncorrectable congenital biliary atresia: its pathogenesis and type of atresia

Histopathologic study was carried out on specimen of extrahepatic biliary system in 23 patients with congenital biliary atresia, and the data were compared with those obtained from a control group of 43 autopsy cases of newborns and infants. In the control cases, accessory tubulo-alveolar glands were observed around the extrahepatic bile duct, and in addition some small ductules were observed in the area of the porta hepatis. In cases of biliary atresia, characteristic findings were histologically detected at each level of the extrahepatic biliary system. In the area of the porta hepatis, there were many epithelial luminal structures in fibrous tissue with inflammatory infiltrates. Near the confluence, the bile duct completely disappeared to be replaced by fibrosis, and in the area between the porta hepatis and the confluence, granulation tissue surrounded by fibrosis was observed. The epithelial luminal structures in the area of the porta hepatis were thought to originate from the bile duct, draining ductules and accessory glands observed in the normal controls. These structures tended to decrease in number with time. In cases possessing a patent common bile duct, the gallbladder showed many mucous glands and no inflammatory changes. On the other hand, in cases with an obliterated common bile duct, the gallbladder showed chronic atrophic cholecystitis without any mucous glands. The pathogenesis remains unknown, but it is thought that this disorder results from non-infectious inflammatory changes initiated near the confluence of the normally developed bile duct.     

Histologic oddities at the porta hepatis in biliary atresia

Purpose

Highly unusual histologic findings at the porta hepatis in 3 infants who underwent Kasai portoenterostomy for biliary atresia are reported.

Methods

Portoenterostomy was performed using a standard operative technique. Serial transverse sections of the excised portal plate were examined by light microscopy along with sections from the distal extrahepatic biliary remnants, gallbladder, and liver biopsy.

Results

Of 61 consecutive infants who underwent Kasai portoenterostomy for biliary atresia, 3 were found to have highly unusual histologic features at the porta hepatis. All had type 3 biliary atresia. Two had hilar biliary ductules lined in part by squamous epithelium, and the third had a focus of mature hyaline cartilage surrounded by perichondrium adjacent to biliary ductules. In each case, these unusual histologic features were localized to the porta hepatis in the region of the transected portal plate.

Conclusions

The presence of hyaline cartilage at the portal plate is likely to be an expression of defective morphogenesis, thus supporting the concept of disordered embryogenesis in the etiology of biliary atresia. Squamous epithelium within biliary ductules might also reflect a similar mechanism but could alternatively be an unusual metaplastic response to inflammation at this site.     

New clues for the developing human biliary system at the porta hepatis

The human biliary system is formed from the hepatic diverticulum, a structure which develops from the embryonic foregut in the fourth week of gestation. The cephalic portion of the hepatic diverticulum lies within the septum transversum, and gives rise to entodermal cells which become the primitive hepatocytes. The caudal part of the hepatic diverticulum is molded by mesenchyme to form the gallbladder, cystic duct, and extrahepatic bile duct. The gallbladder is initially tubular in shape, and undergoes morphological changes to become saccular during the 11th week of gestation. The extrahepatic bile duct elongates and widens as gestation progresses, and intramural mucus glands develop. There is no solid stage during the development of the extrahepatic bile duct. The extrahepatic bile duct is a well-defined tubular structure by the 6th week of gestation, whereas the intrahepatic biliary system during this period of gestation is represented by the primitive ductal plate. The ductal plate undergoes structural changes from the 11th week of gestation, beginning at the porta hepatis and progressing through gestation to the periphery of the liver. This remodeling process shapes the ductal plate from a flat sheath of biliary epithelium surrounding the portal vein branches into a network of interconnecting tubular structures. Mesenchyme plays an important role in ductal plate remodeling. The intrahepatic biliary system is in luminal continuity with the extrahepatic bile duct throughout gestation at the porta hepatis. The major bile ducts at the porta hepatis are fully formed by the 16th week of gestation. Received: September 30, 2000 / Accepted: January 10, 2001     

The future role of hepatic portoenterostomy as treatment of biliary atresia.

According to our recent study, 38 of 93 patients (40.9%) who underwent portoenterostomy at Juntendo University Hospital between 1977 and 1986 survived for more than 5 years. In order to learn the future improvement of the prognosis of biliary atresia patients who undergo portoenterostomy, we investigated the relationship between the prognosis of biliary atresia patients and the age and the histological changes of liver at the time of surgery. Twenty-seven of 30 patients (90%) who survived for more than 5 years with no jaundice and no findings of liver cirrhosis had a mild degree of liver fibrosis (F1 or F2) and a mild degree of degeneration of intrahepatic bile ducts (B1 or B2) at the time of surgery, in spite of the difference of size of intrahepatic bile ducts at the porta hepatis. On the other hand, all 8 patients who showed severe liver fibrosis (F3) and severe degeneration of intrahepatic bile ducts (B3) did not survive for more than 5 years. Accordingly, we can expect promising prognoses in patients who undergo refined portoenterostomy procedures and receive proper postoperative treatment before they have severe histological changes of liver. The portoenterostomy will still play an important role as treatment of biliary atresia in the future.     

Identification of the jaundiced infant who is likely to recover without surgical intervention.

A series of 32 infants with persistant jaundice in whom an unequivocal differentiation between intrahepatic cholestasis and biliary atresia could not be made is reviewed. A protocol including Lipoprotein-X (LP-X) determinations before and after a short course of cholestyramine (CSM) was carried out in all. A fall in serum LP-X after CSM indicates the presence of patent extrahepatic bile ducts (even microscopic) which will function without benefit of hepatic portoenterostomy. A rise in LP-X levels after CSM means an atretic biliary system. The LP-X, CSM protocol was not able to differentiate between the anatomical variants of biliary atresia that may respond to hepatic portoenterostomy and those that will not. Patent bile ducts (even microscopic) in the porta hepatis and/or proximal hepatoduodenal ligament, which are in continuity with intrahepatic ducts, must be present if hepatic portoenterostomy is to be successful. None of our 12 infants undergoing hepatic portoenterostomy showed evidence of bile excretion after the procedure. Microscopic study of serial sections taken through the excised hepatoduodenal ligament tissues of these 12 infants revealed that none had anatomical findings conducive to the success of the operation.     

HIF-1alpha-pathway activation in cholangiocytes of patients with biliary atresia: An immunohistochemical/molecular exploratory study

BackgroundBiliary atresia is a neonatal disease characterized by choledochal obstruction and progressive cholangiopathy requiring liver transplantation in most patients. Hypoxia-ischemia affecting the biliary epithelium may lead to biliary obstruction. We hypothesized that ischemic cholangiopathy involving disruption of the peribiliary vascular plexus could act as a triggering event in biliary atresia pathogenesis.MethodsLiver and porta hepatis paraffin-embedded samples of patients with biliary atresia or intrahepatic neonatal cholestasis (controls) were immunohistochemically evaluated for HIF-1alpha-nuclear signals. Frozen histological samples were analyzed for gene expression in molecular profiles associated with hypoxia-ischemia. Prospective clinical-laboratory and histopathological data of biliary atresia patients and controls were reviewed.ResultsImmunohistochemical HIF-1alpha signals localized to cholangiocytes were detected exclusively in liver specimens from biliary atresia patients. In 37.5% of liver specimens, HIF-1alpha signals were observed in biliary structures involving progenitor cell niches and peribiliary vascular plexus. HIF-1alpha signals were also detected in biliary remnants of 81.8% of porta hepatis specimens. Increased gene expression of molecules linked to REDOX status, biliary proliferation, and angiogenesis was identified in biliary atresia liver specimens. In addition, there was a trend towards decreased GSR expression levels in the HIF-1alpha-positive group compared to the HIF-1alpha-negative group.ConclusionActivation of the HIF-1alpha pathway may be associated with the pathogenesis of biliary atresia, and additional studies are necessary to confirm the significance of this finding. Ischemic cholangiopathy and REDOX status disturbance are putative explanations for HIF-1alpha activation. These findings may give rise to novel lines of clinical and therapeutic investigation in the BA field.     

In biliary atresia duct histology correlates with bile flow

Three basic types of microscopic biliary structures at the portahepatis were distinguishable in infants with biliary atresia: bile ducts, collecting ductules of biliary glands, and biliary glands. Correlation between the type of biliary structure and the quantity and quality of post-operative bile flow was possible in 23 instances. At 2 weeks after operation, the 11 patients in whom a bile duct was identified had a daily bile flow of 68.0 +/- 11.5 mL. Bilirubin concentration in the bile was 13.6 +/- 3.3 mg/dL and total daily bilirubin excretion was 8.77 +/- 2.74 mg. In contrast, bile flow in 12 patients having only collecting ductules and/or biliary glands in the porta hepatis was 19.1 +/- 3.9 mL and bilirubin concentration in bile was 1.7 +/- 0.3 mg/dL. Thus, total daily bilirubin excretion was 0.34 +/- 0.08 mg (P less than 0.001). Postoperative cholangitis occurred only in patients with ducts. It is concluded that only bile ducts communicate with the intrahepatic biliary system and drain bile after hepatic portoenterostomy.     

Bile ducts and ductules are positive for CD56 (N-CAM) in most cases of extrahepatic biliary atresia

The diagnosis of extrahepatic biliary atresia can be challenging as the histologic features can overlap with other pediatric cholestatic liver diseases. Several previous studies have noted that biliary epithelium is positive for CD56 in the setting of extrahepatic biliary tract disease. Thus, we explored the use of CD56 in evaluating liver biopsy specimens for extrahepatic biliary atresia. A total of 22 cases were selected and immunostained for CD56, including 14 cases of confirmed extrahepatic biliary atresia and 8 cases of other cholestatic liver diseases in which the differential diagnosis included extrahepatic biliary atresia. Bile ducts and proliferating ductules were positive for CD56 in 13 of 14 cases of extrahepatic biliary atresia. The staining intensity was generally strong with most cases showing positivity in more than two thirds of portal tracts. The one negative case was a very small biopsy (<0.3 cm), and sampling may have played a role. In contrast, 4 of 8 cases in the control group were completely negative for CD56, with the remaining cases showing weak and focal positivity. In conclusion, bile ducts and ductules are CD56 positive in most cases of extrahepatic biliary atresia, and CD56 immunostaining can be a useful supplemental stain for diagnosing extrahepatic biliary atresia in its early, ductular proliferative phase when used in conjunction with traditional hematoxylin and eosin morphology and clinical information.     

Roux-en-Y on-line intussusception to avoid ascending cholangitis in biliary atresia

A child with biliary atresia experienced severe ascending cholangitis when the exteriorized loop of a portahepatoenterostomy was internalized. Backwash of bowel contents was reduced and further cholangitis was prevented by creation of an on-line intussuscepted Roux-en-Y jejunal loop to provide a nonrefluxing conduit from the porta hepatis. The loop could then be internalized and antibiotic therapy could be discontinued. The success of this procedure in this case encourages us to use this method in similar cases of biliary atresia. It may be of use in all Roux-en-Y loops, such as those used to drain the transplanted liver of patients with biliary atresia and those created to drain the distal part of the transplanted pancreas.     

Incidence of intrahepatic biliary cysts in biliary atresia after hepatic portoenterostomy and associated histopathologic findings in the liver and porta hepatis at diagnosis.

BACKGROUND/PURPOSE: The association of intrahepatic biliary cysts in biliary atresia (BA) after hepatic portoenterostomy has drawn the attention of many pediatric surgeons and has become an important subject in clinical management, but the incidence and causes of this association are not well known. METHODS: During the last 14 years, we operated on 33 BA patients by hepatic portoenterostomy. Five patients could not be followed up over a 1-year period, so the remaining 28 patients had their intrahepatic structure investigated by periodic magnetic resonance imaging (MRI), and were confirmed at autopsy. The authors also reviewed the preoperative conditions of these patients and the histopathologic changes in the liver biopsy and the porta hepatis specimens taken at portoenterostomy. RESULTS: (1) Intrahepatic biliary cysts were found in 6 of the 28 patients studied (21%). Of 16 patients who were operated on after 1989 and are undergoing follow-up by MRI, 4 (25%) had cysts. (2) Five of the 6 patients with cysts had episodes of cholangitis before or at the time of discovery of the cysts, and 4 of them have had their jaundice reappear since the discovery of the cysts. (3) The intralobular spaces (ILS) with fibrosis and the number of bile ducts had increased in the group with cysts compared with those in the group without cysts. (4) The bile duct maximum size in the porta hepatis (PH) was similar in the groups with and without cysts, but a denudation of the mucosal lining cells in the duct, and a fibrosis and inflammation around the duct had increased in the group with cysts compared with those in the group without cysts. (5) Statistically, the fibrosis found in the ILS and the inflammation around the bile duct found in the PH were induced as a correlative factor affecting cyst formation. CONCLUSIONS: The association of intrahepatic biliary cysts in BA after portoenterostomy is frequent. The fibrous change in the ILS and the inflammatory process around the bile ducts might be potential causes of cyst formation.     

Progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is an important cause of cholestatic liver disease and biliary cirrhosis in pediatric population. Three cases of PFIC are described that were diagnosed on the basis of family history, pruritus, cirrhosis and / or paucity of interlobular bile ducts on liver biopsy and presence of extrahepatic biliary tree on imaging. These patients were initially labeled as suffering from extra-hepatic biliary atresia and neonatal hepatitis. PFIC-1 and 2 could not be differentiated on histological grounds, since these patients presented late and process of fibrosis was advanced.     

Intrahepatic cholangiocarcinoma arising 34 years after excision of a type IV-A congenital choledochal cyst: Report of a case

We report a rare case of intrahepatic cholangiocarcinoma (IHCC) arising many years after excision of a type IV-A congenital choledochal cyst. A 44-year-old man was transferred to our hospital with acute cholangitis more than 34 years after several operations for congenital biliary dilatation. Imaging showed a huge tumor in the left medial section of the liver, extending to the porta hepatis. Although he had no jaundice, the intrahepatic bile ducts showed cylinder-like dilatation with narrowing of the hilar bile duct. At surgery, the tumor was found to arise from the dilated intrahepatic bile duct just above the narrow portion. He underwent a left hepatic trisectionectomy with a vascular procedure. Microscopically, the tumor was confirmed to be moderate-to-well-differentiated tubular adenocarcinoma. Thus, when the narrow segment is left untouched, careful long-term follow-up is important to detect new lesions at an early stage.     

胆道闭锁诊断方法价值分析

胆道闭锁是以肝内外胆管进行性炎症和纤维化为特征的疾病,是导致婴儿持续性黄疸的重要原因,如未得到及时治疗,可迅速发展为肝硬化,患儿最终因肝功能衰竭而死亡,因此胆道闭锁的早期诊断显得尤为重要。胆道闭锁主要依靠术中胆道造影以及肝组织活检确诊,但其具有侵入性、操作复杂、并发症多等缺点,不利于胆道闭锁的早期诊断,相比较而言,一些无创性检查方法如实验室检查、影像学检查等具有明显优势。本文对各种胆道闭锁诊断方法的应用价值进行分析,为其早期诊断提供新思路。     

Experimental study of the pathogenesis of infantile obstructive cholangiopathy and its clinical evaluation

1,4-phenylenediisothiocyanate was given to five groups of rats of different developmental stages (97 in all), and the changes in the hepatobiliary system were compared histopathologically. Three groups of rats given the drug after birth showed dilatation of the extrahepatic bile ducts with inflammation. Two groups given the drug during the fetal period or added after birth showed stenotic or atretic extrahepatic bile ducts due to thickening and fibrosis of the wall. This experimental model suggests that differences in the pathologic features of infantile obstructive cholangiopathy (biliary atresia, neonatal hepatitis, and bile duct dilatation) may be the result of various developmental stages in the pathogenic process. After the experiment, 11 cases of correctable type biliary atresia were compared to 24 cases of noncorrectable type in various aspects. It is suggested that the correctable type may have suffered pathogenic process later in the developmental stages than noncorrectable type.     

一种治疗肝胆管结石和狭窄的术式——皮下通道型肝胆管成形术35例临床分析

对于肝胆管结石的治疗目前已取得了很多成功的经验，但最常使用的胆肠吻合术虽经不断改进，仍未能从根本上解决返流性胆管炎、胃肠分泌功能紊乱等并发症。为此，设计了一种新术式：即皮下通道型胆囊肝胆管成形术。在清除结石，解除肝内外胆管狭窄、肝门整形的基础上，利用胆囊壶腹部切开相应大小的切口与之吻合，并适当游离胆囊，使其底部可以被固定到切口皮下。患者必须具备基本正常的胆囊、肝外胆管和Ｏｄｄｉ括约肌。同时要求术中基本取尽肝内结石或切除病灶。已完成此手术共３５例，所有患者手术顺利，术后未发现并发症。其中１例３年后结石复发，１例２年后发生胆道蛔虫，均经皮下胆囊通道用胆道镜轻易取出。该术式既能处理好结石和狭窄问题，又能保存胆囊、胆管、Ｏｄｄｉ括约肌的功能，保持胃肠道的正常生理通路，并能以最简捷的方法处理术后结石复发和胆道内其它问题     

Bile duct patterns in the hilar region of the liver in two cases of biliary atresia

Bile duct patterns in the hilar region of the liver were demonstrated in two autopsy cases of biliary atresia by three-dimensional graphic reconstructions. In one case, jaundice had completely disappeared after successful hepatic portojejunostomy. However, at the age of 4 months, this patient died of cardiac failure caused by endocardial cushion defect. The histological reconstruction of this case showed that there were large patent bile ducts, 150 microns to 400 microns in diameter, and plenty of bile ductules surrounding the large ducts to form networks. The other patient died of hepatic failure at the age of 9 months. In this case, only a few large ducts ended in bile lakes that did not connect with the portojejunostomy, and only a few ductules were found around the large ducts. These results indicate that the existence of networks of bile ductules and the patency of large bile ducts at the porta hepatis contribute to good postoperative bile excretion.