Prognosis of extrahepatic bile-duct atresia after hepatoportoenterostomy

 Clinical and histologic findings from 206 patients operated upon for extrahepatic biliary atresia (EHBA) are analyzed in order to define the prognosis of patients with EHBA. The prospective study took into consideration both initial fibrosis of the liver and the morphology of the porta hepatis (PH) at surgery. Kaplan-Meier survival estimates and statistical calculations demonstrated a relationship between long-term survival and histologic findings in the liver and porta hepatis. The efficacy of HPE is significantly influenced by the morphology of the PH and to a lesser extent by the initial liver fibrosis. Surgery should thus achieve pattern 1 morphology of the PH, but this is problematic because of the close relationship of the vascular and biliary structures in its two lateral zones. Accepted: 8 November 1999     

Evaluation of prognostic criteria in extrahepatic bile duct atresia

Extrahepatic bile duct atresias must be classified into four histopathological groups according to the characteristic numerical, metrical, and morphological alterations of the interlobular bile ducts. A prospective study based on an observation period of 5 and more years included 43 patients with extrahepatic biliary atresia. It showed that prognosis is generally dependent on three factors: (1) the duration of cholestasis; (2) the structure of the bile ducts in the praehilaeren Versclussplatte; and (3) the histopathologically defined features of the interlobular bile ducts. The total diameter of all bile duct structures in the praehilaeren Verschlussplatte is unmistakably the most significant finding. A total diameter of more than 400 m indicates a favorable prognostic subtype, while a total diameter of less than 400 m is unfavorable. Even if the prognostically favorable type of finding is present, the ultimate prognosis is determined by the histopathological features of the interlobular bile ducts. Therefore, four characteristic groups must be taken into consideration when evaluating prognosis.     

Association of oesophageal atresia and cholecystohepatic duct

A rare hepatobiliary malformation in which the common hepatic duct drains directly into the gallbladder or the cystic duct (cholecystohepatic duct) is described in two children born with oesophageal atresia. Attention is drawn to the rarity of this combination. A brief review of the literature of cholecystohepatic and accessory hepatic ducts is also presented.     

Biliary atresia with a “cyst at porta”: management and outcome as per the cholangiographic anatomy

The purpose of this study is to classify biliary atresia (BA) with a "cyst at porta" according to the cholangiographic anatomy and to define management strategy and outcome in each group. A cyst at porta was identified in 13 of 58 babies (22.4%) with BA at first presentation. The cholangiographic anatomy was classified as; Group A (n = 7), type III BA with extrahepatic cyst; Group B (n = 2), type I or II BA with extrahepatic biliary cyst; and Group C (n = 4), type I or II BA with both extrahepatic and intrahepatic biliary cysts. The remaining 45 patients were comprised of type III BA without a cyst. A Kasai's portoenterostomy (PE) was performed for all Group A patients. Groups B and C were treated by hepaticojejunostomy (n = 5) or portoenterostomy (n = 1). All 45 patients with type III BA without a cyst were treated by a Kasai's PE. The median age at surgery was 92 days (ranges 28-342 days). There were three early post-operative deaths, all in patients with type III BA without cyst. Overall 18/55 (32.7%) patients achieved a jaundice free state. In Group A, 5/7 (71.4%) patients had bile flow, 2/7 (28.6%) are anicteric and 2/7(28.6%) had 1-2 episodes of post-operative cholangitis. In Group B, both patients are anicteric and none had post-operative cholangitis. In Group C, all four babies had bile flow but, significant morbidity because of recurrent severe cholangitis. Only one patient reached a jaundice free state. Of the remaining 42 patients with type III BA without a cyst, 27 (64.3%) had bile flow, 13 (31%) became jaundice free and 14 (33.3%) have had 1-2 episodes of post-operative cholangitis. In conclusion, thirteen of 58 (22.4%) babies with BA had a "cyst at porta" at first presentation in this series. The outcome was most satisfactory in type I BA without intrahepatic cystic dilatation (Group B) in terms of achieving a jaundice free state and freedom from recurrent cholangitis. However, intrahepatic biliary cysts (Group C) were associated with recurrent severe cholangitis and a poor eventual outcome despite a good initial bile flow. The outcome in type III BA with extrahepatic cyst was comparable to type III BA without cyst.     

Spontaneous resolution of intrahepatic bile cysts in two patients with biliary atresia after hepatoportoenterostomy

Intrahepatic bile cysts were found in two girls after successful hepatoportoenterostomy for the treatment of extrahepatic biliary atresia, in the first case during a biliary tract infection; one of the cysts persisted after the infection had abated and finally resolved 3 years later. The cyst in the second case induced jaundice and resolved spontaneously after 3 months. Correspondence to: M.-S. Kong     

胆道闭锁Kasai术后超声随访的应用价值

目的综合分析胆道闭锁Kasai术后的超声图像,明确超声检查对于临床随访的应用价值。方法回顾性分析2014年3月至2015年9月在本院进行随访的胆道闭锁患儿超声检查结果,对部分阳性图像及参数与天冬氨酸转移酶-血小板比值(APRI)进行比较,根据黄疸消退情况进行分组,分析各组间超声随访指标的差异。。结果不均质肝脏的APRI[0.36(0.21~0.65)]明显高于均质肝脏[0.11(0.06~0.14)]和欠均质肝脏[0.19(0.12~0.32)],P0.05;包膜欠光整和包膜高低不平患儿的APRI[分别为0.33(0.18~0.58)]和0.44(0.27~0.67)],明显高于包膜光滑者[0.19(0.10~0.31)],P0.05;肝脏半定量评分与APRI之间呈正相关,并且有统计学意义(ρ=0.42,P0.05)。肝内胆管囊性扩张患儿APRI[0.46(0.35~0.65)]高于阴性患儿[0.23(0.13~0.42)],两者差异有统计学意义(P0.05)。术后时间6~12个月及≥12个月组中,肝静脉衰减指数(HVDI)与APRI之间均具有明显的正相关性(ρ分别为0.65及0.49,P0.05)。脾肿大患儿APRI[0.33(0.19~0.57)]高于脾脏大小正常患者[0.14(0.09~0.21)],P0.05。黄疸消退C组的肝脏评分[5(4~7)]明显高于A组和B组(P0.05);B组和C组的脾肋下长度[34.9(20~45)mm,35(23~40)mm]均明显大于A组[18(0~30mm)],P0.05。C组中的脾肿大、腹水阳性、单相波比例均明显大于A组(P0.05),C组的三相波比例明显小于A组(P0.05)。结论将肝实质回声、肝表面包膜进行半定量评分可用于评估肝纤维化和手术预后;肝内胆管囊状扩张者肝纤维化程度会更为严重;对于术后6个月以上的患儿,肝静脉呈单相波或波形平坦的双相波对于提示肝硬化具有参考价值;脾肿大(特别是脾肋下长度≥20 mm)和患儿的手术预后较差相关。     

Cell cultures of bile duct epithelium and the pathogenesis of biliary atresia

The pathogenesis of biliary atresia is unknown. The authors describe a technique for culturing extrahepatic bile duct epithelial cells of human and bovine origin in monolayer cell cultures. Light-, electron microscopy and immunohistological studies prove the epithelial nature of the cultured cells.Inoculation of the cells with reovirus 3 showed no destruction; adenovirus 6, herpes simplex and polio virus 1 and 2 destroyed the cells within 24 h.The cells produce a growth factor maintaining the integrity of the cells, even in the absence of serum.     

Alcohol injection into an intrahepatic cyst for recurrent infection after portohepatoenterostomy

A 2-year-old female with recurrent infections after hepatoportoenterostomy is reported. An intrahepatic cyst appeared to be the source of the recurrent infections. Short-term percutaneous drainage of the cyst was performed three times, but the cyst persisted and there was recurrent fever. We then introduced pure alcohol into the cyst twice through a drainage catheter; there was a prompt decrease in discharge from the cyst, which gradually decreased in size and disappeared 8 months later. There were no further episodes of infection. It was apparent that the alcohol injections were very effective in treating the recurrent infections.     

Betamethasone in plus phenobarbitone prior to hepatobiliary scintigraphy increases diagnostic accuracy in infants with jaundice

Objective. In the diagnostic work up of the child with neonatal obstructive cholangiopathy (NOC), hepatobiliary scintigraphy (HBS) determines the need for peroperative cholangiography (POC). Traditionally, phenobarbitone is recommended to prime the liver to HBS. This retrospective study was designed to evaluate whether addition of the betamethasone (BM) alters the diagnostic accuracy of the HBS in distinguishing neonatal hepatitis (NH) from extra hepatic biliary atresia (EHBA).Methods : Between 1993 – 1999, 202 patients presented with NOC and this study was not designed as a prospective randomized clinical trial. Of these, 126 patients had received Phenobarbitone (Group I) and the remaining 76 (Group II) had received BM in addition to the PB in a dose of 5 mg/k/d and 2.2 mg/k/d respectively for 7 days prior to HBS.Results : Retrospective analysis revealed that, in the Group I, 41 showed excretion and 85 did not show any excretion of the radiopharmaceutical and the latter underwent POC which revealed that 31 patients (36%) of them showed patent biliary tract. In group II, 32 patients revealed excretion and 44 did not show any excretion of the radiopharmaceutical and the latter had undergone POC, which revealed that only 8 patients (18%) showed patent biliary tract. The percentages of false positives (36% vs 18%) was statistically significant (p<0.03).Conclusion : Addition of BM increases the diagnostic accuracy of the HBS and this would lead to decreased need for POC to distinguish NH from EHBA.     

胆总管未闭锁型胆道闭锁的手术治疗及疗效分析

目的 分析24例胆总管未闭锁型胆道闭锁的临床疗效,旨在指导临床对此类胆道闭锁的手术方式进行选择.方法 回顾分析我院1995至2006年间收治的24例胆总管未闭锁型胆道闭锁患儿手术、术后病理及随访资料.对空肠肝门吻合(A组)与胆囊肝门吻合(B组)在自体肝生存率、黄疸清除率、反流性胆管炎发生率及临床疗效等方面比较分析;并对胆道闭锁胆囊病理标本及正常对照组胆囊进行胶原纤维Van Gieson染色和CD68免疫组化染色,比较其纤维化及炎性反应的差异.结果 平均(51±29.02)个月随访期内,自体肝生存率为66.7%.A组自体肝1年生存率为78.6%,3年生存率78.6%;B组1年生存率为66.7%,3年生存率33.2%,两组3年生存率差异有统计学意义(P＜0.05);A组术后6个月黄疸清除率明显高于B组(86.7%比33.3%,P＜0.05);术后1年胆管炎发生率,A组为60.0%,B组为44.4%(P＞0.05).胆道闭锁患儿胆囊表现为明显纤维化和CD68阳性细胞浸润.结论 胆囊肝门吻合治疗胆总管未闭锁型胆道闭锁的疗效较肝门空肠吻合差,可能与胆囊肝门吻合后残余胆道存在纤维化及炎症细胞浸润有关,对其治疗推荐采用肝门空肠吻合.     

胆道闭锁肝内胆管上皮E-cadherin的表达及其与细胞凋亡相关性研究

目的研究胆道闭锁(biliaryatresia,BA)肝内胆管上皮Ecadherin的表达及胆管上皮细胞凋亡情况,初步探讨其与BA发生的关系。方法应用Ecadherin免疫组化染色方法和末端脱氧苷酸转移酶介导的脱氧三磷酸尿苷(Dutp)缺口末端标记技术(TUNEL法)观察38例胆道闭锁患儿与16例正常对照儿童肝内胆管上皮Ecadherin表达及胆管上皮细胞凋亡情况。结果胆道闭锁患儿肝内胆管上皮Ecadherin表达强度0.33±0.12较正常对照0.62±0.20显著降低(P<0.01),胆管上皮细胞凋亡指数为0.5174±0.1993明显高于正常对照0.1234±0.1932(P<0.01),BA组肝内胆管上皮Ecadherin表达强度与胆管上皮细胞凋亡指数呈显著负相关(r=-0.853)。结论BA发生与肝内胆管上皮Ecadherin异常降低有关,可能是通过异常降低的Ecadherin上调胆管上皮细胞凋亡数量,导致肝内胆管发育障碍,产生“胆管板畸形”的方式来实现的。     

Extrahepatic biliary atresia: from diagnosis to liver transplantation

Thirty infants were diagnosed with extrahepatic biliary atresia (EBA) from July 1978 to July 1989; 28 have undergone a Kasai or Lilly-Altman modification of the Kasai portoenterostomy; 2 were excluded from surgery because they presented after 3 months of age and had advanced biliary cirrhosis. Immediate postoperative drainage (>30 ml/day was achieved in 24 patients (86%), with 14 (50%) surviving free of jaundice. The average follow-up was 2.25 years (range 3 months to 10 years); the longest survivor is 10.3 years old. The overall survival was 64%, and 5-year survival 50%. Of 24 infants operated on at <12 weeks of age, 14 are free of jaundice (58%), 4 are alive with jaundice (17%), and 6 have died (25%). No correlation existed between subsequent bile drainage and duct size at the porta hepatis, presence or absence of hepatic fibrosis, giant-cell transformation, or hepatic inflammation. Complications included cholangitis (57%), progressive hepatic failure (39%), portal hypertension (21%), gastrointestinal bleeding (21%), esophageal varices (18%), stomal hemorrhage (11%), seizures (7%), rickets (3.5%), biliary calculus in the Roux-en-Y (3.5%), and hepatic abscess (3.5%). Five infants required revision, with 1 patient undergoing six reoperations, each followed by successful re-establishment of bile drainage. One infant had a successful liver transplant, and 2 are currently candidates for transplantation. Based on this analysis, an algorithm has been formulated for the diagnostic evaluation and subsequent surgical management from initial portoenterostomy to orthotopic liver transplantation for infants diagnosed with EBA. From our review of this experience and the literature on EBA and orthotopic liver transplantation, we have concluded that portoenterostomy has a substanial chance (P <0.05) of providing bile drainage and survival is comparable to that after liver transplantation. Although ultimate failures occur at a steadily increasing rate, portoenterostomy delays transplantation until children are older and can more easily undergo transplantation with its attendant risks of immunosuppression and complications.     

Multiple gastrointestinal atresias with cystic dilatation of the biliary duct

A term newborn developed signs and symptoms of an upper-intestinal obstruction. A palpable transverse upper-abdominal mass was identified. An ultrasound examination demonstrated a cystic mass with massive dilatation of the biliary tree. At laparotomy, dozens of segmental intestinal atresias (IA) from the jejunum to the rectum were identified. The cystic mass was the duodenum, obstructed distally from the atresias and proximally from an antral web. The biliary dilatation was due to normal drainage into a closed-loop duodenal obstruction, and was relieved by division of the web. The multiple atresias were explored, but establishment of intestinal continuity was impossible. The entity of multiple segmental IAs in association with cystic biliary dilation has been previously described, but there are no recorded survivors; 35 patients have been reported in the world literature. Our patient was the longest survivor; she finally died after 2 years of gastrostomy-tube drainage and total parenteral nutrition while awaiting intestinal transplantation. Only 5 patients other than ours had documented immune-system abnormalities. We review the findings and management of this rare syndrome. Accepted: 19 April 1999     

Porcelain gallbladder with extrahepatic bile duct obstruction in a child

An extrahepatic bile duct obstruction was diagnosed in a 13-year-old boy presenting with pruritus, abdominal pain and jaundice. Several weeks after sphincterotomy and biliary stenting via endoscopic retrograde cholangiopancreaticography which relieved the obstruction, the patient was operated on. Severe fibrosis encased the extrahepatic biliary tract, so only cholecystectomy was performed because planned hepaticojejunoanastomosis could jeopardize the vascular supply to the liver. Histopathology showed calcification of the gallbladder wall and chronic fibroproliferative changes in the surrounding tissue. The stricture of extrahepatic biliary duct resolved after 3 years of repeated replacement of stents. The stenting was thereafter terminated. In the following 3 years no dilation of intrahepatic bile ducts and no laboratory signs of cholestasis recurred and the now 19-year-old boy is doing well. Neither a case of porcelain gallbladder with extrahepatic bile duct obstruction in a child nor a successful treatment of the obstruction by long-term stenting has been described in the literature yet.     

A case of biliary atresia with cystic dilatation of the extrahepatic bile duct and polysplenia syndrome

A 79-day-old girl presented with jaundice and acholia. Laboratory findings disclosed elevated levels of bilirubin, transaminases, and gamma-glutamyl transferase. A chest X-ray film showed dextrocardia. A computed tomographic scan revealed a cystic mass at the porta hepatis, multiple spleens in the right side of the abdomen, and absence of the inferior vena cava. Under the diagnosis of biliary atresia (BA) (I-cyst) associated with polysplenia syndrome, a hepatic portojejunostomy was performed at 80 days of age. The postoperative course was uneventful, and the jaundice cleared. Although the occurrence of associated anomalies in BA is rare, polysplenia is most commonly seen, and its incidence is reported to be 2% to 10%. Patients with BA and polysplenia usually have a poor prognosis, however, this patient may have a good prognosis due to uneventful recovery from the jaundice. Accepted: 30 August 1999     

Ectopic pancreas associated with a choledochal cyst and extrahepatic biliary atresia

Two children with incidentally-diagnosed ectopic pancreatic tissue in the jejunum at surgery for extrahepatic biliary atresia (EHBA) and choledochal cyst (CC) are reported. No case has been reported in the literature describing the association of a CC with ectopic pancreas, and only one case of EHBA associated with ectopic pancreas has been reported. We believe that incidentally-detected ectopic pancreatic tissue should be excised, even though the patient is symptom-free, in order to prevent the risk of serious complications due to either the mass effect or the potential for acute pancreatitis, cystic degeneration, or malignant transformation at a later date. Accepted: 12 December 2000     

Isolation and culture of biliary epithelial cells from bile duct remnants of patients with biliary atresia

Biliary atresia(BA), the most common cause of obstructive jaundice in infancy, has been considered to be a result of progressive destruction of the bile ducts through a necroinflammatory process. Many immunohistochemical studies of BA remnant have been done, but it has not been shown that biliary epithelial cells (BECs) can be cultured from BA remnant. For this study, we obtained bile duct remnants from three patients with biliary atresia (one male, two females) who received Kasais operation from 2002 to 2003. The successive cultivation rate of BECs from explants was 100% (3/3 patients). Culture of BECs on collagen gel was possible up to at least four passages. Under a phase-contrast microscope, primary and passed cultured cells on collagen gel showed a cobblestone-like spread in 2 weeks. The BECs had immunoreactivity to anti-human cytokeratin 7 antibody. In this study, we proved that BECs in the remnants of BA could be cultured, and defined the maturation of biliary epithelial cells of BA by immunocytochemistry with anti-human cytokeratin 7 antibody. In conclusion, BECs in BA remnant are alive, and their proliferation activity can be maintained.     

Biliary atresia: Early diagnosis through operative cholangiography

A retrospective analysis of 17 infants with biliary atresia was carried out. The role of operative cholangiography for diagnosis is emphasised for early intervention and better prognosis.     

Notch配体、受体在小儿胆道畸形肝组织中的表达及意义

目的 探讨Notch信号通路在小儿胆道畸形发病机制中的作用.方法 收集23例胆道畸形患儿临床资料(胆道闭锁12例,胆总管扩张11例),术中取肝脏组织样本;9例正常肝脏组织样本作为正常对照.免疫组化方法和实时荧光定量PCR方法检测肝脏组织中的Notch配体、受体的表达分布和相对表达量.结果 Jag1在胆道闭锁增生胆管表达明显增强,Jag2在各组门管区表达为阴性;荧光定量PCR显示:胆道闭锁组及胆总管扩张组Jag1 mRNA的表达明显高于对照组(P＜0.01);Jag2 mRNA的表达在三组问差异无统计学意义(P＞0.05).Notch1、Notch 2在对照组及胆总管扩张组主要表达于肝细胞和成熟胆管细胞,胆道闭锁组胆管细胞无阳性表达.Notch 3在胆道闭锁汇管区新生血管、基质中有较为明显的表达.荧光定量PCR显示:Notch1、Notch 2mRNA的表达在三组间差异无统计学意义(P＞0.05),胆道闭锁组Notch 3 mRNA的表达高于对照组(0.013±0.003比0.009±0.003,P＜0.01).Notch 4表达为阴性.结论 胆道闭锁肝脏组织Notch配体、受体表达异常,增生胆管细胞Jag1的过表达及Notch受体表达缺陷可能参与了胆道闭锁的病理过程.     

胆道闭锁Kasai术后类固醇辅助治疗的现状和研究进展

本综述介绍了胆道闭锁Kasai肝门空肠吻合术后的类固醇辅助治疗方案,总结了历年国际及国内范围对于该辅助治疗的临床试验报道,综合对类固醇基础研究的文章,分别从类固醇作用机制、临床应用方案、不良反应及近年循证医学证据等方面进行了详细的描述,在讨论中提出目前仍需实行多个前瞻性临床随机对照试验以重复观察及评价胆道闭锁术后类固醇辅助治疗的利弊.