空肠胆支引流物与胆道闭锁术后胆管炎的关系

对13例胆道闭锁术后患儿，进行胆支排出物研究。胆汁细菌阳性率８３％，且菌种常发生变化。胆管炎发生预兆是，胆汁排出量减少，颜色淡，含胆红素降低。胆汁中间接胆红素上升。且经造瘘口排出固体物亦增加，这些固体物中有炎症细胞、细菌菌落和真菌。临床上根据这些改变。作出早期诊治。     

胆道闭锁患儿早期胆红素变化

目的：比较胆道闭锁及婴儿肝炎综合征（以下简称为婴肝）患儿出生后2个月内胆红素水平,分析胆道闭锁和婴肝患儿胆红素变化的规律,探讨胆道闭锁患儿胆红素水平与年龄的内在联系。方法选择2000年1月至2009年4月因黄疸于出生后60 d 内行血清胆红素检查的胆道闭锁患儿68例,为胆道闭锁组;2005年1月至2009年4月因婴儿肝炎综合征于出生后60 d 内行血清胆红素检查的患儿72例,为婴肝组;正常对照组为近1年内非肝脏疾病于出生60 d 内行胆红素检查的54例患儿。分析各组血清胆红素水平随年龄变化的特点,并计算检查时年龄、直接胆红素与总胆红素的比例。将上述结果分组进行对比分析,研究各组血清胆红素与年龄之间的关系。结果胆道闭锁患儿血清总胆红素、直接胆红素水平明显高于婴肝组患儿（P ＜0.05）。胆道闭锁组患儿出生后10 d 内血清总胆红素、直接胆红素水平明显高于婴肝组和正常对照组。胆道闭锁组患儿直接胆红素水平、直接胆红素与总胆红素比值随年龄增长缓慢升高,而婴肝组患儿直接胆红素水平、直接胆红素与总胆红素比值在出生20 d后变化甚微。结论胆道闭锁患儿总胆红素水平在新生儿期逐渐下降,1个月后再缓慢升高;且并不是一开始就表现为以直接胆红素升高为主的高胆红素血症,出生后20 d 内其与婴肝相似,均表现为以间接胆红素升高为主的黄疸。年龄小于2个月的婴儿,直接胆红素占总胆红素的水平超过0．7可以作为诊断胆道闭锁的线索。     

十二指肠内胆红素光吸收值监测在胆道闭锁诊断中的应用研究

目的本研究对〈4个月阻塞性黄疸婴儿十二指肠内的胆红素进行光吸收值动态监测，评价光吸收值在胆道闭锁诊断中的意义。方法研究对象分为胆道闭锁患儿（biliary atresia，BA）17例（男11例，女6例；年龄2～16周，平均5．7周）及婴儿肝炎综合征患儿（infantile hepatitis syndrome，IHS）20例（男14例，女6例；年龄3～7周，平均5周）。37例患儿接受了Bilitec十二指肠内胆红素光吸收值的监测，观察原始光吸收值曲线图，分析、比较最高光吸收值、光吸收值≥0．14U及≥0．25U的时间百分比。结果胆道闭锁组的光吸收值明显低于婴儿肝炎综合征组。结论十二指肠内胆红素光吸收值监测可为鉴别BA与IHS提供客观依据。     

胆道闭锁术后高胆红素血症并胆管扩张二次手术的探讨

目的 探讨胆道闭锁(BA)术后高胆红素血症者二次手术的条件及必要性、可行性和效果.方法 2001年3月至2007年12月,共对10例BA术后患儿实施了二次手术,男4例,女6例;年龄5个月～6.5岁.距第一次Kasai's手术时间2个月～6年.其中Ⅲ型BA Kasai's手术后9例,Ⅱ型BA囊肿空肠吻合术后1例;所有患儿第一次术后3个月总胆红素(TBIL)直接胆红索(DBIL)曾降至正常,谷草转氨酶(AST)、谷丙转氨酶(ALT)等酶水平下降,后再次出现高胆红素血症、酶水平升高、陶土样便等情况.二次术前经影像学检查证实所有患儿肝门、肝内胆管扩张,1例并发肝门胆管结石;6例伴有肝门部囊肿形成.结果 8例患儿行开腹肝门空肠再吻合术,2例患儿实施囊肿空肠吻合术,手术全部成功,无术中并发症发生.手术时间为2.6～3.2h(平均3.0h),术中出血15～30ml.术后进食中位数时间32h(24～52h);术后2～4d(平均3d)排黄色大便;腹腔引流放置中位时间58 h(38～96 h),黄疸减退至轻度或消退中位时间为术后12 d(7～24 d),6例患儿术后4周 TBIL、DBIL,降至正常水平,4例患儿6周后降至正常水平,转氨酶术后均下降.术后中位住院时间15 d(12～29 d).术后随访4～36个月,3例患儿于术后4周内发牛胆管炎,2例患儿于术后6个月内发作胆管炎2次,均治愈.术后3个月所有患儿 TBIL、DBIL、总蛋白(TP)正常;3例患儿术后3个月AST、ALT、ALP恢复正常,3例术后5～8个月恢复正常.生长发育正常.无吻合口狭窄、粘连肠梗阻等术后并发症.结论 对BA术后高胆红素血症患儿恰当的实施二次肝门肠吻合术能够建立有效的胆汁引流,改善患儿症状,提高生活质量,并长期带自体肝脏生存,避免肝移植或为等待肝源提供时间保障.     

胆道闭锁术后真菌感染

目的 探讨胆道闭锁手术后真菌感染发生的原因、危害性和诊治方法。方法 对近14年来本科行Kasai手术的131例胆道闭锁患儿的临床资料进行分析。比较手术前、后浅层和深部组织发生真菌感染情况，统计术后真菌性胆管炎发生率。结果 35例发生皮肤真菌感染或口腔鹅口疮。60例胆道造瘘患儿，从造瘘口收集物进行检查，19例为细菌感染，14例发生胆道真菌感染，其胆道排出物可见真菌。另5例发生细菌和真菌混合感染。1例发生真菌性脑脓肿，并致死亡。结论 阻塞性黄疸手术后应用大量激素和广谱抗生素，可能是术后易发生真菌感染的原因。深层真菌感染可引起严重并发症，甚至死亡。胆管炎不仅可由细菌引起，也有可能是真菌感染所致。     

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。     

胆道闭锁肝门空肠吻合术后胆管炎

为了了解胆管炎的临床特点以及对预后的关系。对２４例胆道闭锁术后患儿进行胆汁，胆汁排出物及其临床瑰丽研究。２４例胆道闭锁均行肝门空肠吻合术，２３例术后有胆汁排出，胆汁排出率９５％。１６例术后发生胆管炎２７次。结果：胆管炎前后以及有这炎前兆时胆汁量以及胆汁中胆红素含量均有变化。     

胆道闭锁Kasai术后生存分析

目的 探讨胆道闭锁患儿Kasai术后各因素对生存期的影响。方法 对51例胆道闭锁Kasai术后患儿进行回顾性分析,观察生存时间,以Kaplarr—Meier法描述生存曲线,收集可能影响预后的若干因素,运用Cox比例风险模型,进行统计分析。结果 术后胆汁引流量和是否长期随诊,积极治疗影响生存时间。全组3个月、6个月、12个月的累积生存率分别为69．15％、56．33％、32．50％,中位生存期为8个月;手术日龄越大,中位生存期越短。结论 Cox多因素分析认为：术后胆汁引流量和是否长期随访、积极治疗是影响生存时间的相关因素。手术日龄不同,生存曲线有较大变化。     

胆道闭锁肝胆病理改变与预后的关系研究

目的 通过研究BA患儿术中肝活检和肝门纤维块的病理表现,探讨肝脏和纤维块病理表现与BA预后的关系.方法 2009年4月至2010年9月,61例BA患儿在我院行Kasai手术治疗,术中取肝活检和肝门纤维块.病理切片观察肝小叶结构、纤维化情况,将所有BA患儿根据肝病理诊断是否为胆汁性肝硬化分为肝硬化组和非肝硬化组.根据镜下观察到纤维块中小胆管增生的程度分为少许小胆管增生组和较多小胆管增生组.术后随访3～17个月.结果 病理诊断为肝硬化者术时年龄较大、术中门脉测压较高、术后肝功能恢复情况较差.肝硬化组术后3个月黄疸消退率明显较非肝硬化组低(X2=4.020,P=0.045),术后1年病死率明显较非肝硬化组高(P=0.046).肝硬化者纤维块内小胆管增生程度较重(x2=4.244,P=0.039);纤维块内小胆管增生越严重,术后3个月黄疸消退率越低(P=0.045).结论 肝病理检查是较早的评估BA患儿预后的可靠方法,肝硬化是影响BA预后的重要因素;纤维块小胆管增生程度与BA患儿的短期预后有相关关系,但其是否与BA的远期预后有关系还需要进一步的研究.

Abstract：

Objective To investigate the correlation between the pathologic changes of liver and fibrous portal tissue and prognosis of biliary atresia (BA). Methods Between April 2009 and September 2010, the Kasai's procedures were carried out on 61 patients with BA. Specimens of the liver tissue and fibrous portal tissue were collected in operation. The pathology of the liver tissue and fibrous portal tissue was studied. Based on the severity of hepatic cirrhosis, the patients were grouped into two groups: cirrhosis group and no cirrhosis group. According to whether or not there was obvious bile ductular proliferation in fibrous portal tissue, the hepatic cirrhosis patients were further grouped into 2 groups. All of patients with BA were followed up for 3 to 17 months. Results The patients of hepatic cirrhosis group were older at operation, and had higher portal pressure and poorer prognosis. The 3 months post-operative jaundice clearance rate of cirrhosis patients was significantly lower than that of no cirrhosis patients (39. 5% vs 83. 3%,X2 = 4. 020,P= 0. 045). The 1-year post-operative mortality of the cirrhosis patients was significantly higher than that of no cirrhosis patients (53. 3% vs 0,P= 0. 046). The patients of the cirrhosis group had more bile ductular proliferation (60% vs 0, X2 = 4. 244, P = 0. 039). The more severe bile ductal proliferation in the cirrhosis patients was, the lower jaundice clearance rate they would have (76. 5% vs 38. 5%,P=0. 045). Conclusions The pathologic findings of liver can be used to predict the prognosis of the BA patients after Kasai's procedure. The patients with severe hepatic cirrhosis and bile ductal proliferation have poor prognosis.     

胆道闭锁Kasai术后相关预后因素分析和对策

目的 探讨影响胆道闭锁(biliary atresia,BA) Kasai术后预后的相关因素,了解我省BA的治疗现状.方法 回顾性分析2009年1月至2015年12月间,在山西省儿童医院行腹腔镜探查、胆道造影确诊胆道闭锁后行Kasai术且随访资料完整的91例患儿.采用Kaplan-Meier法计算各亚组患儿自体肝存活率.各亚组之间自体肝存活率的比较应用Log-rank检验,多因素分析采用COX回归模型.结果 全组患儿6个月、1年、2年的自体肝存活率分别为76.9％(70/91)、48.3％(44/91)、36.3％(33/91).按手术日龄将患儿分为:＜60 d(34例)、60～90(含60)d(47例)、90～120(含90)d(8例)和≥120 d(2例)组,各组2年累计自体肝存活率分别为55.8％(19/34)、44.7％(21/47)、12.5％(1/8)和0(P=0.047).男、女童2年累计自体肝存活率分别为36.4％(16/44)和46.8％(22/47),差异无统计学意义(P=0.313).有胆管炎发作组(67例)与无胆管炎发作组(24例)的2年累计自体肝存活率分别为31.3％(21/67)和62.5％(15/24)(P=0.011);黄疸消退明显组(61例)和黄疸消退不明显组(30例)的2年累计自体肝存活率分别为50.8％(31/61)和23.3％ (7/30) (P=0.012);肝功能恢复良好组(53例)和肝功能恢复较差组(38例)2年累计自体肝存活率分别为56.6％(30/53)和21.1％(8/38)(P=0.01);Ⅰ型、Ⅱ型、Ⅲ型闭锁的2年累计自体肝存活率分别为77.8％(7/9)、66.7％(4/6)和31.6％(24/76)(P=0.023),差异均有统计学意义.结论 手术日龄、有无胆管炎发作、黄疸消退情况、肝功能恢复情况及胆道闭锁分型为影响Kasai手术预后的影响因素,其中手术日龄、黄疸消退和肝功能恢复情况是影响生存的独立预后因素.提高民众对胆道闭锁的认知水平,加强术后随访评估,对提高胆道闭锁生存率有重要意义.     

同源异形盒基因HEX单核苷酸多态性与胆道闭锁病因的相关性

目的 检测胆道闭锁(BA)患儿HEX基因的单核苷酸多态性(SNPs),探索HEX基因的单核苷酸多态性与BA发病的相关性.方法 Ⅲ型BA的患儿30例,经术中胆道造影确诊,男17例,女13例,年龄1～5个月,其中1～2个月10例,2～3个月12例,大于3个月8例.同期住院的非胆道畸形患儿20例为对照组.提取外周血白细胞的DNA,对HEX基因的全部4个外显子进行PCR扩增,PCR产物直接测序,判定HEX基因单核苷酸多态性的位置和类型及其与BA发生可能存在的相关性.结果 30例BA患儿中,共发现3个多态性位点,其中5例患儿存在第1个外显子24G/A多态性位点;3例患儿存在第3个外显子29T/G多态性位点;1例患儿存在第1个外显子274G/A多态性位点.出现多态性位点的女8例,男1例.第1个外显子的2种多态性在人类基因组计划多态性数据库和继往的研究中未见报道.正常对照组未见上述改变.结论 BA患儿存在3个HEX基因多态性位点,由于HEX基因与胚胎时期肝憩室的发育过程有关,该基因的多态性改变可能影响蛋白的翻译及表达的过程,进而影响胆道系统发育.     

The relationship between procollagen-III-peptide and the severity of esophageal varices in children with biliary atresia after Kasai operation

Biliary atresia (BA) is a common cause of infantile cholestasis. Disease progression leads to intra hepaticfibrosis, and thus to the development of PH and EV. Our objective has been to study the relationship between procollagen-III-peptide (PIIIP) and the severity of EV in children with BA after Kasai operation. Children below 15 years of age (n=29) with BA after a Kasai operation were evaluated for EV by endoscopy. Healthy (n=26) children of the same age and sex distribution who participated in the hepatitis B vaccination program served as the controls. Serum PIIIP was determined by radioimmunoassay. The BA patients were classified on the basis of severity of EV (Paquet's classification) into three groups: group 1 (n=15) had grade 0, group 2 (n=8) grade 1–2, and group 3 (n=6) grade 3–4 EV. In group 3, serum PIIIP (2.9 ± 1.3 IU/ml) was significantly higher than in group 2 (1.5 ± 0.4 IU/ml) (P < 0.05). Serum PIIIP levels were increased in group 2 compared with group 1 (1.2 ± 0.4 IU/ml) and in group 1 compared with the control group (1.2 ± 0.2 IU/ml), but this difference was not significant. PIIIP levels increased with severity of the EV in the BA patients. Hence, high PIIIP levels may serve as a non invastive indicator of EV developing in postoperative BA patients. Accepted: 8 January 2001     

胆道闭锁异常肝组织蛋白筛查及预后相关性研究

目的 初步鉴定胆道闭锁肝组织异常蛋白表达情况,寻找与胆道闭锁发病和预后有关的差异表达蛋白.方法 用固相pH梯度双向凝胶电泳分离胆道闭锁和正常肝脏组织总蛋白,银染显色,Melanie3.02 2D图像分析软件分析,对部分蛋白质点用基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)进行鉴定,查询数据库鉴定差异蛋白质.结果 获得了背景清晰、分辨率和重复性较好的双向凝胶电泳图谱,蛋白质匹配率达800%以上.胆道闭锁和正常组比较发现表达量变化达2倍以上的蛋白点有33个,表达量变化达4倍以上者有8个.胆道闭锁预后较好者和预后不好者比较发现表达量变化达4倍以上的蛋白点有22个,表达量变化达5倍以上者有18个.质谱鉴定其中15个点,其中7个点鉴定成功,分别是Viperin、SARM1、GPC3、APC、THUM2、MIA3和KIAA0649.结论 本研究成功鉴定出部分与胆道闭锁发病和预后有关的蛋白质,为进一步研究胆道闭锁致病机制和提高手术预后提供了新的研究方向,有进一步研究的价值.

Abstract：

Objective To investigate the expression of hepatic protein in patients with biliary atresia(BA), and find the relationship between the significant protein and prognosis of biliary atresia.Methods Immobile pH gradients isoelectric focusing was used as 1D, and vertical SDS-PAGE as 2D.Sliver staining, Melanie3. 02 2D analysis software, matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and NCBInr database searching were used to separate and identify the proteome from liver in patients with biliary atresia. Results Satisfactory 2DE patterns were obtained. Thirty-three protein spots were remarkably changed in patients with biliary atresia compared with the control group. Twenty-two protein spots were significantly difference between BA patients with good prognosis and BA patients with poor prognosis. Fifteen protein spots were referred to mass spectrometry, and 7 protein spots were identified, including Viperin, SARM1, GPC3, APC,THUM2, MIA3 and KIAA0649. Conclusions In this study, proteins related to the prognosis and pathogenesis of biliary atresia were identified, which may contribute to prognosis and pathogenesis of biliary atresia.     

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.     

胆道闭锁患儿5种嗜肝DNA病毒感染状况检测报告

目的 检测几种常见嗜肝DNA病毒在胆道闭锁患儿肝脏组织中的感染率,探讨其与胆道闭锁发生的关系.方法 用荧光定量PCR(FQ-PCR)检测随机选取的85例胆道闭锁和10例对照组患儿肝脏组织中的5种嗜肝DNA病毒,包括人巨细胞病毒(HCMV)、腺病毒(ADV)、EB病毒(EBV)、单纯疱疹病毒(HSV)和乙肝病毒(HBV),同时进行石蜡切片的病理染色和巨细胞病毒晚期蛋白PP65免疫组化方法检测.结果 在85例胆道闭锁患儿肝脏组织中,嗜肝DNA病毒阳性56例(65.9%),其中HCMV阳性51例(60.0%),ADV阳性5例(5.9%),EBV阳性3例(3.5%),HSV和HBV阳性0例(0%),对照组10例中均未检测到以上病毒的存在.免疫组织化学结果显示:HCMV多集中于肝脏组织中的肝细胞、血管内皮细胞、炎症浸润细胞当中,胆管上皮细胞呈强阳性反应.结论 胆道闭锁与嗜肝DNA病毒感染之间存在相关性,其中以人巨细胞病毒感染关系最为密切.     

Long-term survival after Kasai's operation for biliary atresia

Long-term survival of biliary atresia patients after Kasai hepaticoportoenterostomy is being increasingly reported. Prognostic factors indicative of a favorable long-term outcome consist of: (1) early age at operation; (2) bilirubin excretion of at least 6 mg daily 1 month after operation; (3) favorable hepatic histology at the time of operation; and (4) low incidence of postoperative cholangitis. Jaundice-free long-term survival is now attained in from one-fourth to one-third of patients undergoing Kasai hepaticoportoenterostomy by experienced surgeons in the Western hemisphere. In many long-term survivors there is normalization of liver function, improvement in hepatic histology, and resolution of the complications of portal hypertension. Most patients in this category have made a normal adjustment to their disease and lead active adolescent and adult lives. Offprint requests to: B. A. Stewart