小儿胆道闭锁与肝移植

小儿胆道闭锁是小儿外科有代表性的常见病之一。自然死亡率为 10 0 % ,很少存活过 2周岁。葛西手术打破了 10 0 %死亡的铁门 ,然而晚期效果仍很不满意。肝移植如果能 10 0 %成功 ,则患儿可获得 10 0 %的正常寿命与生活质量。《实用儿科临床杂志》组织这 5篇文章 ,正是为了攀登这个目标而铺路。专家们分别从几个方面介绍了胆道闭锁与小儿肝移植的现代观点与技术。对我们开展此项工作将有很大的帮助。欲求小儿胆道闭锁疗效的提高 ,我认为当前应从以下三方面入手 :　　一、扭转对胆道闭锁的“放弃”态度目前因为许多家长认为其疗效很不满意 ,医…     

胆道闭锁儿童肝移植术后90天再入院危险因素分析

目的 调查胆道闭锁儿童在肝移植术后90天再入院率及危险因素。方法 回顾性分析上海交通大学医学院附属新华医院、仁济医院和上海儿童医学中心确诊为胆道闭锁,2019年1月1日至2019年12月31日首次接受肝移植手术治疗患儿的临床资料。比较再入院组和未再入院组间临床特征,分析再入院的危险因素。结果 共纳入264例患儿,男124例、女140例,中位年龄6.9(5.6～9.4)月。儿童肝移植术后90天再入院率为22.0%(58/264)。与未再入院组相比,再入院组患儿PELD评分、血清总胆汁酸水平、INR较高,住院时间较长,血小板计数、腰肌面积较低,差异均有统计学意义（P<0.05）。二元logistic回归分析示血小板减少症(OR=2.347,95%CI:1.154～4.776)、血清总胆汁酸水平(OR=1.058,95%CI:1.011～1.106)、腰肌面积(OR=0.615,95%CI:0.301～0.989)、住院时间(OR=1.069,95%CI:1.031～1.109)是肝移植术后再入院的影响因素（P均<0.05）。结论 血小板减少症、血清总胆汁酸水平升高、腰肌面积减少...     

胆道闭锁婴幼儿肝移植围术期液体管理

目的 分析胆道闭锁( biliary atresia,BA)婴幼儿肝移植围术期各阶段内环境的变化特点,并探讨相应的液体管理措施.方法 2006年9月至2011年8月我院行胆道闭锁婴幼儿肝脏移植手术24例,围术期连续监测患儿血流动力学,定时采血检测酸碱平衡、乳酸、电解质、血糖等指标,记录液体治疗措施.结果 患儿术中血pH值及碱剩余(BE值)于无肝期即刻下降至术毕接近正常,分别为(7.38±0.09)、(-1.44±0.64),术后开始升高、至术后12h达峰,此后逐渐下降至正常;乳酸于无肝期开始升高(3.31 -±0.8) mmol/L,新肝期30 min达峰,术后6h明显下降,术后12h完全降至正常;血清钾浓度(K+)于新肝期后出现显著下降(3.21±0.52) re mol/L;血清钙浓度(Ca2+)自无肝期出现明显下降(1.03±0.12) m mol/L;血清钠浓度(Na+)于新肝期后出现逐渐升高趋势(141.2±2.9)mmol/l;血糖(BG)于无肝期后明显高于术前水平(7.4±2.8) mmol/L.术后患儿电解质及血糖水平有所波动,但与术后即刻比较无明显变化.24例患儿均顺利完成手术,围术期未发生脱水及心肺事件.术后ICU死亡4例,其余患儿均顺利回到病房.结论 胆道闭锁婴幼儿肝移植围术期内环境呈现规律性变化.术中液体治疗原则与一般腹部大手术有所不同;补液速度相似,但是液体比例以胶体液为主,占液体总量的50 ％以上.术后即期液体治疗与普通外科手术相近.     

胆道闭锁患儿肝移植术后的监护与治疗

目的 回顾分析22例胆道闭锁患儿(23例次,其中1例行再次肝移植)肝移植术后的重症监护管理经验,探讨并发症的发生率以及病原菌与患儿并发症预后之间的联系.方法 统计分析22例平均体重＜8.8 kg的婴幼儿在ICU的相关临床资料,包括药物的使用情况(肾上腺素能激动剂、抗高血压药、利尿剂、镇静止痛药)及主要并发症(排异反应11例,外科并发症16例,感染18例)的诊断、评估及治疗,其中抗生素的选用主要根据药敏试验结果决定.结果 最常见的术后并发症包括感染(18例)、消化道出血(3例)、血管并发症(4例).1例死于原发性无功能肝,11例出现排异反应.最常见的病原微生物包括表皮葡萄球菌(7例),不动杆菌属(6例),铜绿假单胞菌(7例).ICU平均住院时间为10 d,机械通气平均时间37.6 h.多巴酚丁胺、前列腺素E1、多巴胺的平均使用时间分别为3.3 d,7.5 d,8.8 d.术后胃肠外营养的平均起始时间为12 h,进食起始时间平均72 h.结论 术后监护是保证婴幼儿肝移植成功的关键之一.

Abstract：

Objective To summarize experience of pediatric intensive care and explore the incidence of complications, the involved pathogens among liver recipients to determine the effective strategies for preventing complications. Methods Between June 2006 and July 2009, 35 children under the age of 14 yr received 35 liver transplantations (LTs) performed at the center. A retrospective review of 22 infants weighing 8. 8 kg or less underwent 23 transplants was conducted. Indication for transplantation was biliary atresia. Central venous pressure and arterial blood pressure were monitored continuously and fluid monitoring was performed every 2 hours in the first postoperative week. Blood loss, ascites, and intraoperative transudate loss were primarily replaced with 5% albumin and crystalloids to maintain a central venous pressure between 4 and 6 cm H2O. Oral food intake was allowed as soon as possible. To identify vascular or biliary complications, liver doppler ultrasound was performed intraoperatively immediately after reperfusion and after closure of the abdominal wall and postoperatively, twice daily during the first week after surgery.Immunosuppression was initially cyclosporine based, in combination with steroids. Cyclosporine was begun one day prior to transplantation at a dose of 10 mg/( kg · d) divided into two doses, except for cases with hepatic encephalopathy and severe infection. The subsequent doses were adjusted on the basis ofrecommended trough blood concentrations at different stages. Steroids were eventually discontinued at a time point exceeding 6 months after transplantation. The diagnosis of rejection was confirmed by histology on needle biopsy specimens. Acute graft rejection episodes were treated with a 3-day scheme of Ⅳ methylprednisolone 10 mg/( kg · d) followed by recycling doses during the following 3 days (7.5, 5 and 2. 5mg/(kg · d). Results The most common postoperative complications were infections (18 cases),gastrointestinal bleeding (3 cases), and vascular complications (4 cases). Rejection occurred in 25% of patients. There was one perioperative death from primary graft non-function. The most common isolated bacteria of the pathogen spectrum were Staphylococcus epidermidis. The median length of stay (LOS) in the PICU for 22 patients (23 transplants) was 10 days ( range 5-21 ) and the mean length of stay in the hospital was ( 18.5 ± 116) days ( range, 11-48 days). Mean requirement for artificial ventilation was 37.6 h. Mean use of dobutamine, prostaglandin E1 and dopamine was 3.3, 7.5 and 8.8 days, respectively.Preoperatively, 3 children had gastrointestinal bleeding, 18 had ascites, 2 had encephalopathy, 22 had jaundice, and 16 had coagulopathy. There were multiple early operative complications in these infants,including one graft with primary non-function (4. 5% ). Two patients (9. 1% ) returned for a total of three times for gastrointestinal bleeding or intra-abdominal hematoma. Three patients (13.6%) had early postoperative intestinal perforations related to adhesions or enterotomy, one was associated with a bowel obstruction. There were 26 episodes of bacterial or fungal infections in 18 (81.8%) patients in the early postoperative period, and infection was the direct/contributing cause of death in one infant. These infections included pneumonia, intra-abdominal abscess or sepsis. All of the bacterial and fungal infections were successfully treated with the appropriate antibacterial and antifungal agents, except for one patient who developed overwhelming sepsis after small bowel perforation. Four (18.2%) patients developed five episodes of acute allograft rejection during the first 15 days after LT. Three of the four patients who developed rejection were transplanted before 2007. All episodes of rejection were treated successfully with intravenous steroid pulse and optimization of cyclosporine levels or FK506 conversion. Of the 20 survivors beyond the perioperative period, two cases ( 10% ) had hypertension requiring therapy. Conclusions Liver transplantation in infants with biliary atresia appears technically demanding but acceptable. There should be essentially no age or size restriction for infants and transplantation can be performed with good outcome,although the frequency of complications is much higher than that seen in older children. The improvement in medical and nursing expertise in this group of very sick infants is based on judicious preoperative donor and recipient selection, meticulous surgical technique (vascular reconstruction and abdominal closure ),immediate detection and prompt intervention of complications, and keen postoperative surveillance, which reflect a learning curve for both the technical aspects of liver transplantation and post-operative care of these very small patients in our institution. Liver transplantation for infants can be technically challenging.     

肝移植治疗胆道闭锁:附16例报告

目的 探讨肝移植治疗胆道闭锁的疗效.方法 对16例胆道闭锁的患儿实施肝移植手术,其中7例为劈离式肝移植,9例为活体部分肝移植.术后所有患儿均给予抗排斥、抗感染、抗凝及营养支持等治疗,密切监测移植肝血流及肝功能变化,观察术后并发症及预后.结果 16例胆道闭锁患儿全部手术存活,术后早期主要并发症为感染,以细菌感染为主,感染部位主要为腹腔及肺部.死亡2例,1例术后9 d死于感染性休克,1例术后1年死于严重EB病毒感染、溶血性黄疸;其余14例患儿随访1 ～ 4.5年(至2010年12月),检测肝功能良好.结论 肝移植是治疗胆道闭锁安全有效的方法.     

胆道闭锁术后早期胆管炎风险因素分析

目的 探讨影响胆道闭锁术后早期胆管炎发作的风险因素. 方法 对本院2007年1月至2011年12月收治胆道闭锁患儿临床资料进行回顾性分析.所有患儿均采用统一治疗方案,包括手术方式为标准Kasai手术或肝管空肠吻合术,术中胆支引流肠襻45 cm,术后使用激素、抗菌素和利胆药物.将病例以手术年龄、术后黄疸清除效果、Ohi分型和肝纤维化病理分级进行分组,分析影响早期胆管炎发作的原因. 结果 共有139例BA患儿进行手术,124例获得随访.术后35例早期胆管炎发作,发生率为28.3％.术后黄疸完全清除率早期胆管炎发作组低于未发作组（28.2％∶71.8％,P=0.004）,术后1年、2年自体肝生存率早期胆管炎发作组低于未发作组（分别为44.5％±8.5％∶86.5％±3.6％,44.5％±8.5％∶76.3％±4.5％,P=0.003）.Logistic分析显示黄疸清除速度（P=0.000）,肝纤维化病理分级（P =0.029）和Ohi分型基本型（P =0.042）影响早期胆管炎发作而与手术年龄（P=0.579）,Ohi分型亚型（P=0.511）和肝外胆管详细分型（P =0.224）无关.结论 良好的肝门部病变类型,术后较好的胆汁引流和较轻的肝纤维化有利于减少胆道闭锁术后早期胆管炎的发生.     

儿童终末期肝病评分在胆道闭锁患儿肝移植中的应用

儿童终末期肝病(pediatric end-stage liver disease,PELD)评分系统是根据客观的实验室检查数据评估儿童肝脏疾病严重程度的模型,国际上用它来分配日益减少的供肝给儿童肝移植受者.对于Kasai手术效果不佳的胆道闭锁(biliary atresia,BA)患儿来说,肝移植成为唯一的选择.本文通过分析PELD评分系统与经典的临床肝功能Child分级、BA肝移植手术时机的选择、活体肝移植(living donor liver transplantation,LDLT)、肝纤维化、葛西手术(Kasai procedure,KP)以及肝移植手术预后之间可能存在的关联,旨在较全面的了解PELD评分在BA患儿肝移植中所发挥的作用,力求使其应用更加科学、合理.     

肝移植时代肝门肠吻合术在胆道闭锁治疗中的地位

胆道闭锁的病因尚未确定 ,但认为是发生于胎儿后期、生后早期的一种进行性病变[1] 。胆道闭锁是新生儿期梗阻性黄疸最常见疾病 ,在出生成活婴儿中其发病率大约为 1/80 0 0～ 1/15 0 0 0 ,地区和种族间有所差别 ,以亚洲报道的病例为多 ,东方人发病率是西方人的 4～ 5倍。女童多发 ,男女之比约为 1:2 [2 ] 。日本学者Kasai等[3 ] 于 5 0年代后期创立了肝门肠吻合术用于治疗不可矫治型胆道闭锁 ,该研究成果于 195 9年在日本发表 ,并很快在世界范围内被广泛接受和采用。肝门肠吻合手术开展以前 ,大部分不可矫治型胆道闭锁均不能有效治疗 ,平均…     

活体肝移植治疗胆道闭锁:22例单中心诊治经验

目的 总结活体肝移植治疗儿童终末期肝病胆道闭锁(BA)的外科治疗经验.方法 2006年6月至2009年7月,共完成亲属活体部分肝移植治疗胆道闭锁22例.术后平均随访18.5(1至36个月)个月,回顾总结肝移植患儿临床病理资料.结果 22例胆道闭锁患儿中已行Kasai手术9例,20例低于1岁,21例低于10kg.其手术平均时间、平均出血均无差别.供肝受体质量(GR/WR)比3.5(2.1～5.7)%.有27例次术后并发症,包括3例术后出血再手术止血,1例门静脉并发症,肝静脉并发症1例,3例肝动脉并发症,胆道并发症1例.有3例围手术死亡,1例再次移植,急性排斥5例(22.7%).6个月、1年和3年受体生存率分别为86.4%、82.2%和82.2%.结论 受体体重,移植物受体质量比,是否行Kasai手术对肝移植手术效果无影响;适当的供肝质量,细致的手术技巧可增加手术成功率.     

血清内毒素水平在胆道闭锁患儿术后的意义

目的探讨血清内毒素(ET)、透明质酸(HA)与胆道闭锁(BA)患儿术后肝损害、肝纤维化的关系。方法以行肝门空肠吻合(Kasai)术后的BA患儿为BA组(n=38),正常体检儿童(n=12)为对照组;BA患儿根据其胆红素水平再分成黄疸组(n=14)和无黄疸组(n=24)。由自动生化仪测肝功能,鲎三肽基质显色法测ET水平、放射免疫法测HA水平。结果 BA组患儿存在肝损害,血清ET、HA水平均较正常对照儿童高(P<0.05);BA组患儿中,黄疸患儿的肝损害较无黄疸者重,血清ET、HA水平也较无黄疸者高,差异均有统计学意义(P<0.05);血清ET水平与血清总胆红素、谷草转氨酶及HA水平呈正相关(P<0.05)。结论血清ET水平与术后BA患儿肝损害和肝纤维化密切相关,可作为术后判断BA患儿预后的有用指标。     

儿童DCD供肝肝移植术后胆道并发症高危因素研究

目的 分析儿童心脏死亡器官捐献(DCD)肝移植受者术后胆道并发症发生的高危因素.方法 收集天津市第一中心医院2013年3月至2015年3月施行的48例儿童DCD肝移植手术的临床资料,回顾性分析临床因素对受者胆道并发症的影响.结果 48例儿童DCD肝移植受者术后共11例发生胆道并发症,发生率为22.9％.单因素分析显示胆道并发症组与对照组间的热缺血时间(P=0.003)差异有统计学意义(P＜0.05),受体年龄(P--0.998)、受体性别(P=0.094)、MELD评分(P=0.159)、PELD评分(P=0.740)、Child-Pugh评分(P=0.159)、冷缺血时间(P=0.990)、受体ICU逗留时间(P=0.105)、是否发生感染(P=0.930)、有无其他并发症(门静脉狭窄/血栓形成、肝动脉栓塞、DGF)(P=0.268)以及A3O血型是否相容(P=1.106)差异无统计学意义(P＞0.05).多因素分析显示热缺血时间(P=0.020,OR=10.367,95％可信区间为1.451～74.089)是术后胆道并发症的独立危险因素.结论 胆道并发症仍然是儿童DCD肝移植术后的重要难题,热缺血时间是受者术后胆道并发症的独立危险因素.因此选择更短热缺血时间的CDC供肝可以降低儿童肝移植受者胆道并发症的发生率.     

Percutaneous transhepatic cholangiodrainage as a bridging procedure for liver transplantation in biliary atresia

This case report describes a patient with an unusual type of biliary atresia that precluded the Kasai operation but who survived for 2 years and 6 months with percutaneous transhepatic cholangiodrainage (PTCD) and was successfully bridged to liver transplantation. PTCD is recommended when there is no bile excretion after a Kasai operation.     

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.     

APRI评价胆道闭锁和胆汁淤积综合征肝脏纤维化程度的临床意义

目的 探讨肝功能检查和门冬氨酸氨基转移酶/血小板指数(aspartate aminotransferase-to-platelet ratio index,APRI)与肝脏纤维化程度的关系,阐述其在BA肝纤维化评估中的临床价值.方法 收集2006年2月至2011年8月间在我院治疗的胆道闭锁患儿38例和胆汁淤积综合征患儿25例为研究对象.临床观察指标包括肝功能检查,肝脏活检切片,血小板指数;肝硬化程度采用Metavir分类,APRI的诊断性评估采用ROC曲线,应用SPSS 16.0统计学软件进行统计分析.并对本组患儿进行随访,随访时间是3～69个月(平均随访时间:20.7个月).结果 胆道闭锁组患儿ALP、γ-GT、DBIL(564.14±257.75、153.36±97.47、7.55±2.57)较胆汁淤积综合征组患儿存在明显升高(P＜0.05);胆道闭锁肝硬化组患儿Age、ALT、AST、γ-GT(84.50±24.72、225.07±109.68、331.64±130.93、951.07±667.24)较非肝硬化组明显升高,两组差异具有统计学意义(P＜0.05);胆汁淤积综合征肝纤维化组患儿Age、ALT、AST(84.76±14.28、159.92±61.76、238.15±62.60)较非肝纤维化组(54.17±11.17、98.92±58.08、151.17±41.44)明显升高,两组差异具有统计学意义(P＜0.05).患儿绘制APRI的ROC曲线,用于判定肝硬化程度,胆道闭锁组敏感性为79％,特异性为88％;胆汁淤积综合征组敏感性为91％,特异性为79％.胆道闭锁中肝硬化组病死率显著高于非肝硬化组,且自体肝生存情况低于非肝硬化组.结论 肝功能检查可以作为胆道闭锁的初步判断指标,绘制APRI的ROC曲线对于评价胆道闭锁及胆汁淤积综合征患儿的肝脏纤维化情况均有较高准确性和可靠性,可用于预测预后和提早做好肝移植准备,因其简单、无创性可以在临床上广泛应用.     

小儿尸体肝移植探讨

目的　本研究探讨尸体肝移植治疗小儿终末期肝病的方法和疗效。方法　我院分别于2 0 0 2年 4月～ 2 0 0 2年 12月对 5例患儿 (先天性胆道闭锁 4例 ,肝脏血管内皮肉瘤 1例 )进行肝移植术 ,患儿年龄 6个月～ 5岁。减体积肝移植 3例 ,取左半肝和左外侧叶为移植物。割离式肝移植 2例 ,分别取左外后叶和右后叶为移植物。受体行保留下腔静脉的全肝切除术 ,然后将供肝进行原位移植。结果　 5例患儿移植肝重 2 6 0～ 5 6 5 g ,占受体体重1.94 %～ 5 .4 6 % ,4例术后已经健康存活 7～ 15个月 ,1例于术后第 5d死于心功能衰竭。结论　尸体肝移植是治疗小儿终末期肝病的有效方法 ,严格的围手术期管理特别是精确的手术技术是小儿肝移植成功的关键。