胆道抗反流支架在胆道远端恶性梗阻中的应用研究进展

胆道支架是目前姑息性治疗胆道恶性梗阻的重要方法,而支架置入后长期的肠液反流入胆管则是引起支架堵塞和引起胆管炎的重要原因.常规胆道塑料支架通畅时间短,容易出现堵塞,而金属支架则价格昂贵且置入后无法取出.近几年相继出现了抗反流塑料及金属支架的相关临床研究,初步表明了抗反流支架能够有效的延长支架的通畅时间,对改善患者生活质量、降低治疗费用均起到了重要的作用,使其成为了内镜医师及普外科医师的重要关注点之一.     

Oddi括约肌与胆管色素结石形成关系的探讨

目的探讨Oddi括约肌结构及功能异常与胆管色素结石形成之间的关系。方法胆道术后留有T型管的患者123例,使用放射性核素^99mTc—DTPA判断是否存在肠胆反流,以此将患者分为反流组及非反流组,检测空腹血胃动素、胃泌素水平,随机选取53例使用胆道镜测压。采用钡餐透视观察胆管色素结石、非胃肠胆道疾病、胆囊息肉、胆囊胆固醇结石患者的十二指肠降段憩室发生率;十二指肠镜观察原发性胆管色素结石、胆管结石合并胆囊结石、继发于胆囊结石的胆管结石、胆管末端和乳头部炎症狭窄、胆管末端癌和乳头癌、胆囊切除术后综合征患者的十二指肠憩室内（旁）乳头的发生率。结果123例行胆道取石T型管引流术后的患者中有44例检测到十二指肠胆道反流（35．8％）,反流组Oddi括约肌基础压（SOBP）、收缩波幅（SOCA）、胆总管压（CBDP）显著低于对照组（P〈0．01）。反流组血胃动素、胃泌素水平明显低于无反流组及对照组（P〈0．01）。血胃动素与SOBP、血胃泌素与SOBP及CBDP呈正相关。钡餐摄影显示胆总管色素结石患者十二指肠降段憩室发生率达36．62％,明显高于其他3组（P〈0．05）。胆管胆色素结石患者十二指肠憩室内（旁）乳头的发生率明显高于继发于胆囊结石的胆管结石组、胆管末端和乳头部炎症狭窄组及胆管末端癌和乳头癌组（P〈0．05）。结论胆管色素结石患者存在明显的肠胆反流和胆系感染,Oddi括约肌结构与功能状态与胆管色素结石形成密切相关,其解剖及功能异常是胆管色素结石形成的重要原因。     

肠胆反流与胆色素结石形成的关系

目前认为胆色素结石的成因与胆汁淤积,加上胆道细菌产生的外源性β-葡萄糖苷酶分解胆汁中的结合胆红素等诸多因素有关,而且许多研究都认为胆道细菌的来源与Oddi括约肌松弛导致肠胆反流有着密切的关系。笔者总结目前研究现状并结合自己的相关研究与思考,探讨肠胆反流与胆管色素结石形成的关系。     

重视肠液胆管反流的长期影响

在正常解剖和生理情况下，由于Oddi括约肌的屏障作用，肠液并不能进入胆道。但经某些手术废除或破坏了Oddi括约肌的功能，不仅影响了胆汁、胰液排放的调控，也使肠液能轻易地进入胆道。如无胆管系统狭窄，肠液可自由出入胆管，虽对胆管上皮产生一定的刺激作用，病人可不出现明显症状。于是，很多医生便认为，胆肠吻合是一个理想的术式，Oddi括约肌是可有可无的结构，可随意切开或废除。尤其是近年来随着微创外科技术普及，内镜下Oddi括约肌切开术（EST）广泛开展，括约肌受到破坏、出现肠液胆管反流的病例与日俱增。肠液胆管反流究竟产生什么后果、远期影响如何？值得深人探讨。本文参照近年文献，做如下分析讨论。     

隐性胰胆反流75例分析

目的 研究隐性胰胆反流的发生率及其对胆囊上皮不典型增生和癌变的影响.方法 对2006年7月至2008年2月期间择期行胆道手术或行ERCP检查的956例患者常规作胆汁淀粉酶测定,对手术切除胆囊标本行病理检查,观察不典型增生和癌变的发生率.结果 754例患者中发现隐性胰胆反流75例,发生率为9.9%.反流组和对照组胆汁淀粉酶分别为(7701±20 378)IU/L和(16±51)IU/L,差异有统计学意义(P<0.01).反流组中胆囊癌及不典型增生发生率分别为3.4%(2/58)和31.0%(18/58),均高于对照组(P<0.05).反流组中伴有癌变和不典型增生病例的胆汁淀粉酶值高于不伴有癌变和不典型增生的病例(9194±10 399 IU/L vs.2388±2745 IU/L,P<0.01).结论 在胆胰管汇合正常者中隐性胰胆反流是客观存在的,它促进了胆囊不典型增生和癌变的发生.     

原发性胆管色素结石形成原因的阶段性研究总结

目的从多角度研究及探讨胆管色素结石的成因。方法1997—2006年10年间围绕原发胆管结石成因的研究包括对胆管结石及胆汁进行细菌培养及电镜观察:对胆管结石术后病人,放射性核素检测肠胆反流;同样利用该同位素,检测胆系病人肠道通透性;使用金黄地鼠制造胆囊色素结石模型,观察内毒素含量及二胺氧化酶变化,评价肠道黏膜通透性与胆结石的关系;调查胆管结石与胆囊切除术间的关联;观察门奇静脉断流术前后Oddi括约肌运动功能的变化;研究肠胆反流及胆汁排出速度的变化对胆管结石形成影响;钡餐造影研究十二指肠降段憩室与胆管色素结石形成间的关联;观察药物对Oddi括约肌收缩及胆道压力的影响。结果对原发性胆管结石病人结石及胆汁细菌培养表明,胆石中需氧菌阳性率29/30(96.7%);胆汁中需氧菌阳性率33/35(94.2%)。经扫描及透射电镜亦观察到结石内有细菌存在。放射性核素检查发现胆道残石病人中44/123(35.8%)存在明显的肠液反流。胆管色素结石病人肠壁通透性明显升高。胆囊色素结石模型提示金黄地鼠血清中内毒素含量显著高于造模前水平,二胺氧化酶测试亦表明肠黏膜通透性显著升高。调查发现618例胆管结石病人中既往因胆囊结石行胆囊切除者约占12%。切断迷走神经可使消化间期Oddi括约肌张力减低,餐后Oddi括约肌舒张延迟。核素显像对EST前后胆汁排出情况的研究发现,Oddi括约肌切开后胆汁排出明显加快。钡餐造影显示十二指肠降段憩室在胆管色素结石病人中的发生率较高。多种药物可影响Oddi括约肌的运动功能。结论Oddi括约肌受神经体液因素影响,其结构、功能异常是诱发肠胆反流、胆道感染乃至胆管色素结石形成的重要原因。肠道黏膜通透性增高、细菌易位亦与胆管色素结石的形成存在一定关系。     

带蒂胆囊瓣修复肝门胆管狭窄

良性高位胆管狭窄临床常见，多合并肝内胆管结石的炎症性狭窄，通常采用Roux—en—Y型胆管空肠吻合进行外科治疗。这种手术废弃了肝外胆道及Oddi括约肌的生理功能，带来的胆汁流向改变和消化道改建，易造成反流性胆管炎及胆管结石复发。为了保存胆道的生理功能，我们采用带血管蒂的胆囊瓣来修复肝门胆管狭窄与缺损，取得良好的效果。     

间置空肠代胆管在胆道外科的应用

为预防胆道内引流术后肠胆反流发生,对143例需行胆道内引流的病人,选择间置空肠代胆管和人工乳头术,其中胆总管狭窄65例,胆总管囊性扩张症60例,胆总管损伤15例,胆管癌切除5例。通过观察：①胆管和十二指肠引流液淀粉酶测定;②碘剂T管造影;③钡餐造影;④十二指肠镜检。发现间质空肠组胆管液淀粉酶值明显低于十二指肠液;造影剂及钡剂不向空肠段返流。130例人工乳头呈半球形或扁平形粉红色粘膜突起,15例乳头萎缩;术后无上腹痛、低烧、黄疸等慢性胆管炎和再梗阻症状。认为间置空肠代胆管和人工乳头术能有效控制肠、胆返流,从而减少返流性胆管炎的发生。     

肝段(叶)切除胆肠Roux-en-Y吻合加联合抗反流装置治疗肝内胆管结石的治疗效果研究

目的 探讨肝段(叶)切除胆肠Roux-en-Y吻合加联合抗反流装置治疗肝内胆管结石的治疗效果.方法 肝内胆管结石病人230例,其中行肝段(叶)切除联合胆肠Roux-en-Y吻合附加抗反流装置病例103例;行胆总管切开取石、胆总管十二指肠吻合术28例;肝门胆管切开取石、胆管空肠Roux-en-Y吻合术74例;肝总管切开取石、T形管引流术25例.随访时间8～18年.观察手术后近期胸腔积液、切口感染、胆漏、手术后残余结石并发症以及评价远期的治疗效果与结石复发率.结果 各组间胸腔积液、切口感染、胆漏并发症比较无显著性差异(P=0.923).与其他组比较,肝段(叶)切除联合胆肠Roux-en-Y吻合附加抗反流装置组的残余结石率显著性降低(P=0.00),一次取净率有显著性增高(P=0.00),治疗效果显著性提高(P=0.00),结石复发率显著性降低(P=0.00).结论 肝段(叶)切除胆肠Roux-en-Y吻合加联合抗反流对肝内胆管结石具有良好的治疗效果.     

腹腔镜抗反流手术的争议问题

胃食管反流性疾病是消化道常见疾病,严重影响患者的生活质量,正如DeMeester所描述的“反流性食管炎不会夺去患者的生命,却足以毁掉他的生活”。随着抗反流手术的出现,特别是腹腔镜技术的引入,其确切的疗效和较小的手术创伤改变了医师和患者对这种“传统内科疾病”治疗策略的看法,而成为治疗胃食管反流疾病的“金标准”治疗方法。     

Long-term results of endoscopic treatment of biliary stenosis from laparoscopic cholecystectomy

BACKGROUND: The outcome of endoscopic biliary stent insertion for postoperative bile duct stenosis was retrospectively evaluated. METHODS: Fifty-seven patients with biliary stenosis from laparoscopic cholecystectomy were included from February 1992 to January 2000. One to three stents were inserted for an average of 12.4 months, with stent exchange every three months to avoid cholangitis caused by obstruction. RESULTS: Successful stent insertion was achieved in 43/57 (75.4%) patients. Stent insertion failed in 10 patients with complete and four patients with incomplete biliary obstruction. Early complications occurred in four patients. Late complications occurred in 5/43 patients. Five patients experienced recurrence of stenosis. CONCLUSIONS: Endoscopic treatment should be the initial management of choice for postoperative bile duct stetiosis.     

Endoscopic biliary drainage in malignant bile duct obstruction

During a four-year period endoscopic biliary drainage (EBD)--preoperative in 25 and permanent in 45 patients--was successfully established without sphincterotomy in 70 out of 89 referred patients (79%) with malignant bile duct obstruction. 51 of the patients had internal stents and 19 external naso-biliary tubes. There was no procedure-related mortality or severe complications such as perforation or bleeding. One patient, however, got a moderate pancreatitis after stent drainage (1%). In the early drainage period (before operation or discharge) the cholangitis rate was 10%, and during the late period (after discharge) it rose to 27% of the patients. 68 of all 70 patients (94%) had a reduction in S-bilirubin concomitant with clinical improvement and 27 of the 45 patients (59%) with permanent drainage became unjaundiced. Recurrent or increasing jaundice occurred, however, in half the number of these patients (23/45) after an average of 89 days; twelve of them had a temporary regression of jaundice after exchange of stents in spite of advanced disease. The use of multiple stents did not reduce the risk of recurrent jaundice or of cholangitis. It is concluded that EBD inserted without sphincterotomy is a safe and efficient non-surgical alternative in the treatment of malignant bile duct obstruction.     

Use of an opened umbilical vein patch for the reconstruction of the injured biliary tract

Background/Purpose When iatrogenic biliary tract injury occurs, there is the risk of complications such as bile leak and biliary stricture, and hepaticojejunostomy is the conventional procedure used for injury repair. However, this procedure can be complicated by retrograde biliary tract infection and the procedure can destroy the normal anatomical structure. Methods We report here a method of end-to-end biliary tract reconstruction that uses an opened umbilical vein (OUV) patch and two stents to reduce bile leakage and biliary stricture formation following injury to the common bile duct or right main bile duct. The postoperative courses of four patients are reviewed. Results In two of the patients, there was a small amount of postoperative bile drainage (for 3 days in the first patient and 2 days in the second patient). Of the two stents, the first stent was removed 1 month postoperatively, and the second stent at 2 to 3 months postoperatively. Three patients have returned to normal activity without symptoms after 44, 62, and 93 months, respectively. One patient died of a liver tumor recurrence in the fifth postoperative month, without a biliary problem. Conclusions An OUV patch for end-to-end biliary reconstruction reduced the volume and duration of bile leakage. Further research is needed to accurately evaluate the stenting period so as to reduce its duration.     

高位恶性梗阻性黄疸胆道内支架置入治疗的临床应用

目的评价高位恶性梗阻性黄疸胆道内支架置入治疗的疗效及临床价值。方法42例高位恶性梗阻性黄疸病人分别行单侧／双侧穿刺入路，充分胆道内外引流后，置入支架。其中肝总管内置入单枚支架19例；双侧肝管穿刺，行左肝和右肝胆管同时置入支架11例；采用单侧肝管穿刺入路，于左-右肝管间和肝管-胆总管间均置入支架12例。共置入支架65枚，其中3枚为覆膜支架，其余均为自膨式裸支架。结果42例病人中，手术成功率达100％，其中2例病人分别于术后4个月和9个月发生支架内梗阻，行二次介入治疗；1例病人于胆道支架置入术后17个月发生十二指肠梗阻，再行十二指肠支架置入术；1例病人于围手术期因严重胆系感染而死亡．全部病人随访3～112周（平均49周），均获得满意的减黄效果。结论根据不同梗阻部位，采用多种胆道支架置入技术治疗高位恶性梗阻性黄疸是一种安全可靠、疗效确切的姑息性疗法。     

可降解胆管修复材料的研究进展

医源性胆管损伤常用的处理方法,如胆肠吻合,由于放弃了奥狄括约肌功能,近远期有并发逆行性胆道感染、胆管炎,甚至胆管癌的风险。随着临床上对奥狄括约肌功能的重视,有必要寻找能维护胆管功能的修复材料。目前已报道的可降解胆管修复材料具有无免疫原性、暂时性支持作用、降解产物对身体无害等优点,有希望成为可供选择的胆管修复材料。本研究就可降解胆管修复材料的研究进展做一综述。     

腹腔镜经胆囊管开口取石并内支架引流治疗胆囊结石合并胆总管结石

目的:探讨腹腔镜胆囊切除及经胆囊管开口取石并内支架引流术的可行性及临床疗效。方法:2008年1月至2013年1月为28例胆囊结石合并胆总管结石患者行腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)及经胆囊管开口胆管探查取石,内支架引流管引流并一期缝合胆管术。总结其适应证、操作技术及临床疗效。结果:28例均成功完成LC及经胆囊管开口取石并内支架引流术。胆管内取出单一结石19例,2~4枚结石9例。手术时间平均(43.6±19.8)min,平均住院(7.9±3.5)d。26例支架自行脱落并顺利排出体外;2例未自行排出的患者,于1个月后经十二指肠镜行胆道支架取出。未发生胆管结石残留、胆管狭窄、胆漏等手术并发症。结论:LC及腹腔镜经胆囊管开口取石并内支架引流术具有手术时间短、术式简单、术后并发症少等特点,在严格掌握适应证、选择合适病例的情况下,此术式安全、有效、可行。     

Pathology and pathogenesis of intrahepatic bile duct loss

In recent years, the pathology and pathogenesis of bile duct loss have been extensively studied, and a num-ber of hepatobiliary diseases have been added to the list of ductopenic diseases. In addition, the biology of biliary epithelial cells is now being studied with respect to bile duct loss, as well as biliary epithelial neoplasia. In this review, recent advances in pathogenetic and pathological studies of intrahepatic bile duct loss are described, with an emphasis on immune-mediated cholangiopathies. The bile duct loss, an acquired and pathologic process that occurs in the biliary tree, is recognizable as an absence of bile duct in an individual portad tract, and also as such absence in the vicinity of parallel running hepatic arterial branches that constitute the portal triad. Immunostaining with biliary cytokeratin and other carbohydrate materials is useful for the identification of biliary elements in the inflamed portal tracts or fibrous septa. The underlying processes responsible for bile duct loss include immunological, ischemic, infectious, metabolic, and toxic processes. Bile duct loss in primary biliary cirrhosis and primary sclerosing cholangitis is immune-mediated, that in interventional radiology using hepatic arterial branches is related to biliary ischemia, while that in hepatic allograft rejection is related to both immunological and ischemic insults. Bacterial and viral cholangitis with bile duct loss is an example of infectious cholangitis. The biliary tree maintains its homeostasis by renewal and dropout, and bile duct loss occurs mainly via biliary apoptosis. In some patients with bile duct loss, such as occurs in drug-induced injuries, the bile ducts regenerate and finally redistribute in the liver, while in other types of bile duct loss, the loss is progressive and is followed by vanishing bile duct syndrome, leading to biliary cirrhosis or liver transplantation. More analysis of the biology of biliary epithelial cells is mandatory for the evaluation of the pathobiology of bile duct loss, as well as for the effective restoration of biliary epithelial cells, in ductopenic liver diseases. Received: October 12, 2000 / Accepted: January 10, 2001     

Morphological Changes during Creation of a Neo-Bile Duct Using a Vein and a Biodegradable Endoluminal Stent

ABSTRACT?

Major bile duct lesions are usually treated by a hepaticojejunostomy which is often complicated by cholangitis and liver fibrosis. The aim of this study was to investigate the morphologic features of a neo-bile duct created from a vein and a biodegradable endoluminal stent. The neo-bile duct was created using a segment of the external jugular vein which was endoluminally stented by a biodegradable poly-lactate-acid stent. In 18 pigs, the common bile duct was resected and replaced by the vein with (n = 12) or without endoluminal stent (n = 6). Six animals served as controls. Survival, liver function and morphological changes of the neo-bile duct and the liver were observed for six months. After six months, the neo-bile duct morphologically resembled the native bile duct showing Ck7-positive columnar epithelium and newly formed capillaries in the bile duct wall. The biodegradable stent disappeared after four months. All animals survived and showed normal liver function and no cholestasis. In contrast, after sole vein reconstruction of the bile duct, four animals died due to biliary peritonitis and cholangitis. Creation of a neo-bile duct which morphologically resembles the native bile duct is feasible by using a body's own vein and a biodegradable endoluminal stent.     

Endoscopic stenting for malignant biliary obstruction

Use of endoscopic stents to manage patients with malignant obstructive jaundice is a well accepted measure. Interpretation of the results of endoscopic stenting must be made with reference to the level of the bile duct obstruction. Results were generally unsatisfactory for hilar lesions, especially when the intrahepatic ducts were segregated into multiple isolated systems. After deployment, stent dysfunction due to clogging by biliary sludge is apparently an inevitable process for the conventional plastic stent. Considerable efforts had been made to prolong the stent patency by changing its physical configuration, coating the inner lumen, and the choice of material but with little success. The development of a self-expandable metal stent is a major advance, but the benefits derived from a larger stent lumen are compromised by the initial expense and the tumor ingrowth through the wires for all models available commercially. Current data failed to substantiate the value of routine preoperative biliary decompression, as there is no reduction in the morbidity and mortality rates after surgery. Although biased patient selection may have resulted in the negative observations made, repeated clinical trials should probably focus on patients with distal bile duct tumors who are preparing for a major pancreatic resection. As a definitive palliative measure, endoscopic stenting is a more cost-effective option than surgery for patients with limited life expectancy based on data regarding plastic stents. The recommendations are evolving however, as there is progressive refinement of laparoscopic surgery techniques and designs of endoscopic stents.     

Endoscopic biliary stenting: Plastic stent or expandable metallic stent?

Since its introduction 1979, endoscopic biliary stenting has become the method of first choice to treat cholestasis in malignant or benign biliary obstuction or leakage of biliary fistulas. The success rate of endoscopic biliary stenting generally exceeds 90% and procedure-related complications are rare. Although metal stents are becoming more popular, plastic stents are still the first choice. Their major drawback is occlusion with sludge mediated by bacteria. Pharmaco-chemical measures failed to prevent occlusion. With Teflon material and a 10-French stent, stent exchange rates were reduced to 15% in patients with malignant biliary obstruction, the shape without sideholes showing the best results. Stent exchange is easily feasable. Metal stents are expensive and more difficult to handle. Occlusion with sludge is rare, but patency is limited by tumor ingrowth. Metal stents may be indicated in selected patients, such as those with recurrent stent occlusion causing cholangitis. If only a small-caliber prosthesis (7-Fr) can be placed (e.g. in Klatskin tumor) metal stents may have a longer patency than plastic stents. Metal stents should not be used in benign biliary obstruction because these stents are not removable.