胆道闭锁术中胆汁流量及胆汁成分的观察分析

目的 探讨胆道闭锁术中胆汁流量及成分变化与预后的关系.方法 本组对27例BA患儿行Kasai手术时,采用5 ml气体采样管收集和测量从肝门流出的胆汁.以17例胆总管囊肿患儿术中收集的胆汁作为对照组,其中测胆汁流量者7例.采用全自动生化仪检测胆汁中磷脂、总蛋白(TP)、胆汁酸(TBA)、总胆红素(TBIL)、直接胆红素(DBIL)、总胆固醇(TC)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰胺转肽酶(GGT)、碱性磷酸酶(ALP)的浓度.术后随访1～6个月,随访内容有黄疸消退时间、术后血生化、术后胆管炎发生情况.结果 BA组胆汁流量显著低于对照组(P<0.05).手术日龄>60 d的BA患儿及术前血ALT>150 U/L的BA患儿术中胆汁流量均显著低于对照组(P<0.05).术中胆汁流量≥0.19 ml/min的BA患儿术后3个月退黄率显著高于术中胆汁流量<0.19 ml/min的BA患儿(P<0.05).BA组的胆汁磷脂、TBA及DBIL浓度均显著低于对照组(P<0.05);BA组的胆汁ALT浓度显著高于对照组(P<0.01).术后3个月黄疸消除者的胆汁AST及TC浓度均显著低于未消除者(P<0.05).结论 BA术中胆汁流量与预后有明显的关系,患儿术中胆汁流量越好,术后的预后越好,提示术中胆汁流量可以更早地预测患儿的远期效果.BA胆汁成分的变化说明BA患儿的肝功能较差,胆汁中磷脂、TBA和DBIL浓度较低可能是肝脏分泌功能较差的表现.胆汁中的AST和TC浓度与预后有关,胆汁AST和TC浓度较低的BA患儿术后预后较好,可能是由于肝功能较好和胆汁粘度较低利于引流所致.     

胆道闭锁患儿Kasai术后早期胆管炎相关危险因素分析

目的 探讨影响胆道闭锁患儿(biliary atresia,BA)经典Kasai术后早期胆管炎发生的相关因素.方法 对本组中35例BA患儿的临床资料应用二项分类logistic同归分析方法作回顾性分析.结果 胆道闭锁患儿术后近期胆管炎发生与术后胆汁引流效果、术后辅以激素治疗及术中预留胆支长度有显著相关性,而与患儿性别、手术日龄、术前总胆红素及肝功能、手术前后辅以熊去氧胆酸和苯巴比妥利胆退黄治疗、术中设置防反流瓣及术后抗感染力度等因素无关.结论 胆道闭锁患儿Kasai术后胆汁引流效果好,辅以激素治疗,同时术中预留胆支长度充分的BA患儿,其术后不易发生早期胆管炎;反之,患儿发生早期胆管炎风险增加.

Abstract：

Objective To evaluate the factors affecting the early post-operative cholangeitis after classical Kasai operation for biliary atresia (BA) in children. Methods The clinical data of thirty-five BA children from pediatric surgery department of Nanjing Childrens Hospital was retrospectively analyzed using binary logistic regression analysis. Results The occurrence of early cholangitis after classical Kasai operation was found to correlate with post-op biliary drainage effect, hormone therapy and the length of Roux-loop in operation. No correlation could be established between early cholangeitis and sex,age, total bilirubin and pre-op liver function, ursodeoxycholic and luminal therapy, the installation of anti-refluxing valve in operation and the dosage of antibiotics. Conclusions Good biliary drainage,hormone therapy and sufficient length of Roux-loop were associated with decreased risk of early cholangitis.     

早期胆管炎对Kasai's术远期疗效的影响

目的 探讨Kasai's术后胆管炎对胆道闭锁(BA)长期牛存的影响.方法 通过对92例BA行Kasai's术时的手术年龄、术式和术后胆管炎发生等临床资料进行收集和分析,特别是重点分析早期胆管炎对患儿的影响.结果 对1989年3月至1997年3月共92例BA行Kasai's术,手术年龄30～137 d.其中男55例,女37例.失访3例,死亡66例,存活23例巾男14例,女9例,存活患儿年龄最大者现已满19岁.92例中,在出生后60 d内手术25例,现存活5例;61～90 d手术53例.现存活15例.91 d以上手术14例,现存活3例.本组发生早期胆管炎58例,现仍存活7例.19例因肝门部胆管梗阻再次手术,现存活4例.结论 ①胆管炎的处理是BA治疗过程中最困难的一环.胆管炎是BA术后最常见又是最难处理的并发症;②防止早期胆管炎的发生是手术成功的关键,早期胆管炎的危害大.在适宜的年龄进行Kasai's术时,有无胆管炎发生与生存率关系更密切;③对因胆管炎引起的肝门部胆管梗阻应积极治疗;④早期胆管炎不但影响手术后的牛存率,还对远期生活质量有影响.     

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.     

术前营养状态对胆道闭锁术后胆管炎的影响研究

目的 探讨胆道闭锁患儿术前营养状态对术后胆管炎发生的影响.方法 对2014年1月至2014年12月底收入我院的66例经手术探查确诊为Ⅲ型胆道闭锁的患儿采用STRONGKid方法进行营养不良风险评估并分组:低度营养不良风险组,中度营养不良风险组及重度营养不良风险组.通过门诊及电话进行随访,随访内容为首次发生胆管炎的时间,早期胆管炎发生情况及术后3个月内发生胆管炎的次数,术后6个月内黄疸消退情况.结果 低度营养不良风险患儿0例,中度营养不良风险患儿30例(45.5％),重度营养不良患儿36例(54.5％).中度营养不良组首次发生胆管炎的时间(44.31±18.75)d明显晚于重度营养不良组(26.75±7.96)d,P=0.002;中度营养不良组早期胆管炎的发生率13.3％明显低于重度营养不良组66.7％,P=0.04;重度营养不良组患儿术后3个月内胆管炎的平均发生次数(2.11次/人)明显高于中度营养不良组(1次/人),中度营养不良组术后6个月黄疸清除率60.0％高于重度营养不良组16.7％,P=0.014.结论 胆道闭锁患儿术前合并重度营养不良易于发生早期胆管炎且反复发生,中度营养不良组的患儿首次发生胆管炎的时间明显晚于重度营养不良组,重度营养不良组术后黄疸清除率明显低于中度营养不良组.     

Acute intrahepatic portal vein thrombosis complicating cholangitis in biliary atresia

A 2-year-old boy with a Kasai portoenterostomy had systemic features suggestive of cholangitis and acute portal vein obstruction. The rapid rise in portal pressure caused a transient, severe decompensation of hepatic function. A superior mesenteric arterial angiogram confirmed the presence of diffuse intrahepatic portal vein thrombosis. Conclusion This case provides clinical and radiological evidence supporting an association between ascending cholangitis and acute intrahepatic portal vein thrombosis. Received: 7 May 1996 / Accepted: 3 September 1996     

胆汁酸在胆道闭锁疾病中的研究进展

胆道闭锁(biliary atresia)是以进行性肝内外胆管纤维化为特征的疾病,是导致婴幼儿终末期肝病的重要原因,目前病因及发病机制尚不明确.研究表明,胆汁酸可以用于胆道闭锁早期筛查、预后评估及胆管炎诊断.本文对近些年胆汁酸在胆道闭锁中的相关研究进展进行综述.     

胆道闭锁胆汁成分与预后的关系研究

目的 探讨胆道闭锁术中胆汁成分变化与预后的关系。方法 本组对62例BA患儿在Kasai术中收集从肝门流出的胆汁,以25例胆总管囊肿患儿术中收集的胆汁作为对照组。采用全自动生化仪检测胆汁中总蛋白(TP)、胆汁酸(TBA)、总胆红素(TBIL)、直接胆红素(DBIL)、总胆固醇(CHO)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰胺转肽酶(GGT)、碱性磷酸酶(ALP)的浓度。术后随访2～16个月,随访内容有黄疸消退时间,术后血生化,术后胆管炎发生情况及术后1年存活情况。结果 BA组胆汁中ALT(210.13±127.75) U/L、GGT(319.03±206.73) U/L、TP(45.86±18.16)g/L、CHO (0.08±(0.04) mmol/L浓度显著高于对照组,ALT:(69.39±44.55) U/L; GGT:(73.22±99.29)U/L; TP:(21.78±15.36)g/L; CHO:(0.02±0.03) mmol/L(P＜0.05); BA组胆汁中TBA( 189.81±107.81) μmol/L和DBIL (61.31±25.53 )μmol/L浓度显著低于对照组TBA:(735.06±199.75)μmol/L; DBIL:(90.43±27.18)μmol/L(P=0.000和P=0.035)。术前肝功能较好组胆汁中ALT(86.24±65.63) U/L、AST(801.64±516.50) U/L和GGT (205.82±112.25) U/L 浓度显著低于术前肝功能较差组,ALT:(244.67±175.69) U/L; AST:(1409.52±927.05) U/L;GGT:(362.05±235.57)U/L(P＜0.05);术前肝功能较好组胆汁中TBA (346.04±279.33)μmol/L 浓度显著高于术前肝功能较差组(192.47±93.55)μmbl/L(P=0.029)。术后3个月黄疸消退者胆汁TBA显著高于未消退者(251.18±131.83)μmol/L比(121.43±80.42) μmol/L,(P=0.007);术后3个月黄疸消退者胆汁DBIL(72.08±32.51 )μmol/L显著高于未消退者(40.22±23.47) μmol/L (P=0.022)。术后1年存活者胆汁TBA浓度较术后1年死亡者显著增高(258.63±105.63)μmol/L比(110.63±46.08) μmol/L,P= 0.015）;术后1年存活者胆汁ALT浓度较术后1年死亡者显著降低(8.72±8.83)U/L比(95.15±44.18)U/L,P=0.048。结论 BA术中胆汁成分与预后有明显的关系,胆汁中TBA较高、DBIL较高的BA患儿术后3个月黄疸消退较好;胆汁中TBA较高、ALT较低的BA患儿术后1年存活情况较好。胆汁TBA和ALT浓度可作为评价BA短期预后和中期预后的可靠指标。     

Histological assessment of bile lake formation after hepatic portoenterostomy for biliary atresia

Bile lakes develop after hepatic portoenterostomy in some patients with biliary atresia, and have been regarded as an indication of poor prognosis. We reported that bile lakes have no epithelium of the bile duct on their wall, and are surrounded by bile ducts; however, the mechanism of bile lake formation is little known. We investigated histologically how bile ducts are formed using whole removed liver, and the characteristics of bile ducts around bile lakes. From April 1980 to July 2006, we encountered 84 patients with biliary atresia. Bile lakes were analyzed histologically in 11 patients who underwent liver transplantation in our hospital. Bile lakes had a fibrotic cyst wall and lacked epithelia. In most cases, bile stasis, calculi formation, damaged bile ducts, and invasion of inflammatory cells were observed around the bile lakes. Bile ducts around bile lakes were not stained by CD56, but bile ducts around liver lobuli were stained by CD56. The present study speculates that bile lakes would arise from original bile ducts, which are damaged, and fuse together after calculi are formed in bile ducts.     

Efficacy of urinary sulfated bile acids for diagnosis of bacterial cholangitis in biliary atresia

This study evaluated the efficacy of measuring urinary sulfated bile acids (USBA) for diagnosis of bacterial cholangitis in patients with biliary atresia. Eight infants with biliary atresia were recruited. The USBA level was measured when they were admitted to hospital with a fever of unknown origin. Clinical manifestations and laboratory data were reviewed. The standard USBA value for each patient (S-USBA) was defined as the level measured when they had no fever, and USBA ratio (R-USBA) was calculated as the USBA level during the febrile episode divided by the S-USBA. Then R-USBA values were compared between febrile episodes with and without cholangitis to assess the diagnostic ability of USBA. Twenty-three febrile episodes occurred in eight patients during a 15-month period. Nine episodes were diagnosed as being due to cholangitis, five were due to non-cholangitis, and nine were of undetermined origin. The R-USBA value ranged from 1.5 to 15.4 during cholangitis episodes and from 0.4 to 1.2 during non-cholangitis febrile episodes. When fever was of undetermined origin, R-USBA was found to be increased during some episodes and not in others. USBA increased immediately in patients with cholangitis. The measurement of USBA is a useful non-invasive test for cholangitis in patients with biliary atresia who had undergone Kasai’s operation.     

Kasai术后肝内胆管囊性扩张的诊治与预后

目的 总结胆管闭锁术后肝内胆管囊性扩张的诊治经验,分析其对患儿预后的影响.方法 1998年6月至2008年3月,对胆管闭锁行葛西手术的患儿进行追踪随访.通过超声检查,发现8例患儿存在肝内胆管扩张.其中3例再行MRI检查,6例再行CT平扫加增强检杳以明确诊断.此8例患儿术后均有不同程度胆管炎症状.5例行PTCD显示肝内胆管囊性扩张.3例患儿行囊肿与空肠胆支再吻合术,2例患儿仪行PTCD置管引流,2例患儿暂未予任何处理.结果 3例经手术治疗的患儿,术后黄疸消退或减轻.仅行PTCD的患儿肝内胆管扩张长期存在.结论 对反复发作的胆管炎应定期行超声检查,尽早发现肝内囊肿;对肝内胆管囊性扩张,无论其影像学分型如何,应根据其具体临床表现进行相应的积极治疗;PTCD无法长期放置,仅是暂时性的治疗,但对手术时寻找囊肿有指示作用,使手术时囊肿的定位相对容易;囊肿的大小、位置与门静脉的关系,压迫的时间、治疗是否及时有效都可影响患儿的预后.     

胆道闭锁术后胆管炎与肝胆道组织中CD4/CD8+T细胞的相关性研究

目的 了解胆道闭锁肝脏组织和残存胆道组织中T细胞的主要类型及其与Kasai术后胆管炎的关系.方法 应用免疫组织化学的方法对22例胆道闭锁患儿(早期胆管炎和非胆管炎各11例进行配对)肝组织标本和肝门纤维块标本与13例其他肝胆道疾病患儿肝组织标本进行对比研究.同时结合胆管炎的发生与否分析免疫组化结果与Kasai术后胆管炎相关性.结果 胆道闭锁患儿肝脏组织和肝门纤维块内有大量CD4+T细胞和CD8+T细胞浸润(与对照组相比均P=0.000).胆道闭锁组与对照组中CD57+的NK细胞均为阴性.颗粒酶B在胆道闭锁组与对照胆道闭锁组中均为阴性.早期胆管炎组CD8+T细胞数量明显低于非胆管炎组(P=0.002).CD8+T评分与早期胆管炎的发生呈负相关,相关系数R=-0.674(P=0.001).结论 在Kasai手术之前患儿的肝脏组织和残存的胆道组织中有大量CD4+T和CD8+T细胞浸润,而颗粒酶B的杀伤途径不参与胆道闭锁的免疫损伤.CD8+T细胞浸润程度与胆管炎的发生有明显负相关,其对胆道闭锁肝内的损伤性炎症反应可能具有保护性免疫调节作用.     

Long-term outlook in biliary atresia

The oldest survivors from the Kasai portoenterostomy originate in Sendai, Japan and are approaching their 60th birthday. These represent the tip of an expanding cohort of adults born with this previously fatal condition. Increasingly transition to adult-biased hepatologists and physicians will be the expectation of many with this condition. However unlike their usual patients with alcohol, drugs, virally mediated liver disease these are different with different expectations of health and quality of life. Cure is not on the cards for most of these and they survive still with impaired bile flow and increased liver fibrosis and cirrhosis with the threat of cholangitis and portal hypertension still apparent.We review the reported statistics on long-term survival essentially from Japan and Western Europe (such as the UK and France) and the range of complications that may still beset this group.     

A prospective controlled trial of probiotics on cholangitis after Kasai procedure for biliary atresia

目的 探讨益生菌对胆道闭锁(biliaty atresia,BA)术后胆管炎的预防作用.方法 采用前瞻、随机、对照的研究方法,对60例获得知情同意的Ⅲ型BA术后患儿按照手术后是否辅以益生菌治疗随机分为实验组(30例)和对照组(30例).测定患儿血清总胆红素(TB)、直接胆红素(DB)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,结合术后胆汁排出率和随访获得的黄疽消退率及胆管炎发生率综合评定益生菌对胆道闭锁术后胆管炎的预防作用.结果 实验组和对照组患儿平均手术年龄为(52.75±34.30)d和(55.87±29.23)d,手术前各项血生化指标TB(131.49±41.40)μmol/L和(120.16±47.68)μmol/L、ALT(161.01±30.06)μmol/L和(150.21±36.24) μmol/L经统计学分析差异均无统计学意义(P＞0.05),术后2周时两组胆汁排出率为93.3％和90.0％,差异无统计学意义(P＞0.05).随访结果表明术后3个月、6个月时实验组与对照组的胆管炎发生率为58.6％和62.1％、52.0％和54.2％,疗效指标差异均无统计学意义(P＞0.05).结论 益生菌对胆道闭锁术后胆管炎的发生无明显预防作用.     

Coincidental cases of primary sclerosing cholangitis and biliary atresia in siblings?

Familial cases of primary sclerosing cholangitis or biliary atresia have been reported, although genetic influences and immunopathological abnormalities in these diseases are considered to be obscure. We report a case of primary sclerosing cholangitis and biliary atresia in siblings with the observation of HLA-DR antigen expression in the abnormal bile duct epithelial cells.     

胆小管增生诱导胆道闭锁早期肝纤维化

目的观察门管区胆小管增生与肝纤维化的关系，进而探讨胆小管增生对胆道闭锁病程的作用和意义。方法选取在1997-2003年间经我科治疗的胆道闭锁(17例)和婴儿肝炎综合征(19例)患儿。术中肝活检标本石蜡切片行常规HE染色和免疫组化染色(Cytokeratin-7，Ki67)，观察手术时年龄、肝纤维化、胆管增生、胆管增生活性和术前直接胆红素水平。结果在胆道闭锁组，不同肝纤维化级别的胆小管增生级别有相关关系(rs=0．561，P=0．019)。结论大量的胆管迅速增生，诱导产生大量的基质沉积于门管区，可能就是胆道闭锁患儿肝纤维化迅速进展的主要原因。     

Long-term outcome of hepatic portoduodenostomy with interposition of the ileocecoappendix for biliary atresia

Hepatic portoduodenostomy with interposition of the ileocecoappendix (HPI) can be used for the surgical treatment of biliary atresia (BA). The purpose of this study was to evaluate the long-term outcome of patients with HPI. The records of nine patients who had HPI performed for BA were reviewed. Mean age at portoenterostomy was 68.1 days (range 26–113 days). At the end of 2006, seven of the nine subjects were alive, although two required liver transplantation (LT). The two deaths occurred 94 days and 2 years after HPI due to varicella infection and variceal bleeding, respectively. Length of follow-up for the seven survivors ranged from 17 to 19 years (mean 18 years). Three subjects achieved normal liver function after HPI and have remained jaundice-free to date. Another three who were initially jaundice-free required Roux-en-Y jejunostomy (RYJ) to the ileocecum for severe obstructive cholestasis 6 months, 3 years, and 19 years after HPI secondary to stones in the cecum. RYJ was successful in these three cases, and liver function returned to normal within a few months. Two of these three have continued to have almost normal liver function, but one required LT 5 years after RYJ. The remaining case had LT because of liver dysfunction 14 months after HPI. There is a high risk for stone formation and obstruction with the HPI procedure because bile can stagnate in the ileocecum.     

胆道闭锁术后反复发作性胆管炎的细菌谱分析及抗生素选择

目的探讨先天性胆道闭锁肝门空肠吻合术（Kasai术）后胆管炎患儿的细菌谱及抗生素选择。方法收集本院2002年至2009年Kasai术后反复发作胆管炎患儿,选取其中有血或胆汁细菌培养阳性结果者88例,分析常见致病菌及其对抗生素的敏感情况。结果88例胆管炎患儿致病菌依次为铜绿假单胞菌、大肠杆菌及肠球菌,其中铜绿假单胞菌、大肠杆菌对头孢吡肟的敏感率分别为62％、81％,对美罗培南的敏感率分别为100％、96％;肠球菌对万古霉素的敏感率为81％。结论美罗培南可作为对头孢菌素耐药胆管炎患儿的经验首选用药。     

Reappraisal of the role of the bilioenteric conduit in the pathogenesis of postoperative cholangitis

The incidence of postoperative cholangitis has changed very little despite progressive improvement in the treatment of biliary atresia. The role of the bilioenteric conduit in its pathogenesis is still uncertain. A retrospective study of 39 patients undergoing either a conventional Kasai operation (group 1, n = 20) or with placement of an antireflux valve (group 2, n = 10) or lengthening (group 3, n = 9) of the jejunal conduit from 40 to 60 cm was performed to compare the incidence of cholangitis. Postoperative cholangitis developed in 18 of the 39 patients (46%). The incidence was 10/20 (50%) in group 1, 5/10 (50%) in group 2, and 3/9 (33%) in group 3 (P = 0.679). An animal experiment was conducted concomitantly to compare quantitative bacterial cultures of the bilioenteric anastomosis and the liver before and 1 week after Roux-en-Y hepaticojejunostomy (HPJ) in piglets without (group A, 25 cm) and with (group B, 50 cm) lengthening of the jejunal conduit in a porcine model of extrahepatic biliary obstruction. The growth of bacteria in both the bilioenteric anastomosis and the liver was not affected by lengthening the jejunal conduit from 25 to 50 cm (P = 0.612 and 0.057, respectively), despite a geometric increase in bacterial concentrations in both groups after HPJ. It is concluded that neither bacterial growth in the liver nor cholangitis following bile-duct reconstruction was affected by valving or lengthening the bilioenteric conduit. Accepted: 6 June 1999     

Oesophageal atresia and biliary atresia: a rare association

Oesophageal atresia is known to be associated with cardiovascular, gastrointestinal, genitourinary and skeletal anomalies. Its association with biliary atresia is very rare and only a few cases have been reported in the literature. Although biliary atresia could be part of a multiple anomaly syndrome, its isolated occurrence is even rare. We present a case of oesophageal atresia associated with biliary atresia.