【作者】 卢再鸣；

【导师】 郭启勇；

【作者基本信息】 中国医科大学 ， 影像医学与核医学， 2007， 博士

【摘要】 前言恶性梗阻性黄疸是由各种恶性肿瘤引起的不同部位的胆管狭窄或闭塞,而至临床上产生黄疸的一组病例,仅不足10%的病例通过外科手术治疗可以去除梗阻原因,而且手术创伤大、风险大,术后生存期较短。介入放射学医生在传统经皮经肝胆管造影的基础上,发展成为引流术并留置内支架,完成胆道成型术,改善了病人生存质量。在病人黄疸去除,肝功能恢复之后,许多学者主张尚需进一步治疗。我国胆系介入研究大多数为小样本,以及技术改进等方法学研究,对于生存时间及生存率研究很少涉及,引流术与成形术的比较研究更少,许多研究者热衷于留置内支架而忽略引流术,综合介入治疗恶性梗阻性黄疸的疗效尚存争议。而肝门部胆管癌、胆管癌栓更是外科治疗较为棘手的领域。作为临床前实验的重要组成部分,动物实验已经成为胆管支架临床应用研究的基础。由于胆管树的解剖结构和胆汁的化学成分与人类相似,猫、狗和猪成为胆管支架体内动物试验模型常用的动物。论文一正常犬胆管内支架经皮置入的可行性与置入后早期病理变化胆管病理变化的研究目的探讨经皮经胆囊犬胆总管金属支架置入动物模型的安全性和可行性;了解支架植入后早期的病理学改变。资料与方法成年健康家犬10只(22.5kg-29.5kg),禁食24小时后全麻。行CT扫描定位胆囊,观察胆囊与周围肝与肺组织的关系,选择远离肺组织且胆囊体积适宜的穿刺点,并标记。超声引导下于定位点穿刺胆囊,向胆囊内注入造影剂,使胆囊及肝外胆管显影,应用引导装置及硬导丝将5F鞘送入胆总管内,经皮经胆囊管将金属支架置入胆总管分叉处及壶腹部。术后定期检测肝功,术后即刻及术后1个月行CT检查上腹部,观察一个月后处死两只动物,其他试验动物继续观察进行长期研究。术后2个月观察局部胆管的病理学变化。结果在10条狗中,胆囊穿刺成功率为100%。胆总管金属支架置入成功率为80%(8条),另两条狗由于胆囊管与胆总管成角锐利,而使支架植入失败。成功放置支架的实验动物中,7条狗术后状态良好,1条狗于术后24小时死于胆汁漏。在一个月的观察期内,肝功正常的实验动物为4条,两只狗的碱性磷酸酶在术后5-10天升高,一条狗的总胆红素升高,但上述动物均未出现临床症状,且在术后18及30天复查时均恢复正常。在观察期内CT扫描各实验动物支架均未出现明显移位。支架植入后2个月胆管内皮无明显增生,局部有轻微的炎性反应,光学显微镜下可见淋巴细胞增多,电镜下胆管内皮细胞线粒体增多。结论我们成功建立了以犬为试验动物的经皮经胆囊途径胆管介入的动物模型。试验证明该动物模型安全、可行,且适合于长期的试验研究。犬正常胆管置入支架后早期仅为轻微的炎症反应。论文二金属内支架治疗复杂型肝门部胆管癌的临床应用研究目的探讨应用金属内支架治疗复杂型肝门部胆管癌,特别是侵犯肝内胆管的肝门部胆管癌(部分BismuthⅡ型、Ⅲ型、Ⅳ型)的介入治疗方法。资料与方法经临床、生化、影像及手术病理证实的肝门部胆管癌45例,其中男27例,女18例。年龄39-79岁,平均58.4岁。其中4例曾行外科手术,因肿瘤侵袭范围较广无法切除肿瘤而仅行“取组织行病理学检查”和“内引流术”,即术中将硅胶管连接肝管及十二指肠,治疗后黄疸无显著下降或2个月内黄疸复发,其余41例均为首次治疗。全部病例率先行PTBD(percutaneous transhepatic biliary drainage,PTBD经皮经肝胆管引流术),并发肝脓肿的5例同时行脓肿引流术,胆管造影证实除汇合部、肝总管狭窄之外,病变尚累及双侧肝内胆管,其中左右肝管狭窄,二级分支通畅者(BismuthⅡ)12例(n=12);左右肝管狭窄,右侧至少1组二级分支开口部狭窄17例(Ⅲa,n=17);左右肝管狭窄,左侧至少1组二级分支开口部狭窄10例(Ⅲb,n=10);左右肝管狭窄,双侧均至少1组二级分支开口部狭窄4例(Ⅳ,n=6)。使用1～5条引流管充分引流后,置入胆管金属内支架(北京安泰公司,直径6～10mm,长度30～80mm)。一点穿刺双支架T型置入:左或右侧肝内胆管穿刺引流后,将5F导管鞘置入肝内胆管,并经鞘置入双导丝,选择性将导丝分别置入另一叶肝管和胆总管,再分别置入两枚内支架,支架形态呈T型。左右两点穿刺双支架Y型置入:左及右侧肝内胆管分别穿刺引流后,分别将两条导丝置入胆总管,再分别置入两枚内支架,支架形态呈Y型。两点穿刺双支架X型置入:右侧两肝段穿刺或左及右侧肝内胆管分别穿刺引流后,置入导丝分别将两条导丝置入另一叶肝管和胆总管,再分别置入两枚内支架,支架形态呈X型。多点穿刺多枚支架置入,保证一枚内支架置入胆总管(置入胆总管的支架选择直径最大)。支架置入后保留1条引流管,并闭管48小时以上,配合抗炎治疗,无发热腹胀症状则拔除引流管。如出现上述症状,则开放引流管3～5天后再闭管,7天后拔管。统计学分析:使用SPSS11.0和SAS8.1软件。配对t检验分析治疗前后胆红素变化;Kaplan-Meier分析支架开通情况与生存期。Cox比例危险率模型分析性别、年龄、分型对生存期、支架开通时间有无影响结果45例患者共置入引流管73条,内支架96枚,其中39例(Ⅱ、Ⅲ型)使用2枚内支架,6例(Ⅳ)使用3枚内支架。支架均成功置入,其中14例行2枚支架T型置入(右肝穿刺10例,左肝穿刺4例),18例行2枚支架Y型置入,7例行2枚支架X型置入。2例行2枚支架Y型置入后,保留引流管并闭管。患者在48小时内出现发热及周身不适,再次造影显示仍有部分肝段胆管引流不畅,遂选择仍有扩张的一组胆管穿刺并置入第3枚支架。1例患者手术证实肝门部胆管癌,行姑息性胆囊胆总管切除及硅胶管“内引流术”,术后黄疸略有缓解,但50天后黄疸再次加重,穿刺后胆管造影显示各肝段胆管开口汇合处均显示狭窄,于是行3枚支架(6mm/40mm 2枚,8mm/50mm 1枚)置入,即左肝穿刺S2段肝管,在S2S6肝管之间留置第一枚支架,穿刺S7段胆管,在S7S3肝管间留置第二枚支架,再穿刺S8段肝管与胆总管之间留置第三枚支架,之后成功拔除引流管;5例直接留置3枚内支架。支架置入后闭管24小时内还有5例患者出现低热及轻微腹胀,再次开放引流管,引流3～5天后再次闭管,引流管在支架置入后1周内均成功拔除。治疗后胆红素与治疗前相比明显下降(P＜0.05)。没有与支架置入相关的严重并发症出现,出现的并发症包括少量出血(自愈)4例,胆管炎/发热3例;1例支架置入后26天死于肝功衰竭,30内死亡率2.2%(1/45);4例支架置入1个月后出现发热和胆红素上升,其中2例抗生素治疗后好转,2例出现肝脓肿,引流后好转;支架置入后中位随访时间180天,26例仍存活;生存期间5例出现黄疸再发,3例再次置入内支架,2例仅行引流治疗,造影证实支架内闭塞(上口或支架内),闭塞率22.2%(5/45);平均支架开通时间181.5天(26-473天);平均生存时间215.3天(26-516天);Cox比例危险率模型分析结果:年龄、性别、Bismuth分型与支架开通、生存期无关;Kaplan-Meier分析支架开通时间181.5天,95%CI(101.2-279.5天)、生存时间215.3天,95%CI(124.7-303.6天)结论对于复杂型肝门部胆管癌,胆道内支架治疗是一种有效的改善病人生存质量的方法。特别对于病变侵犯肝内胆管的病例,应选择不同的穿刺路径及支架留置方法,尽可能解决更多肝段的胆管引流。治疗后23例认为生活质量提高(85.2%),包括发热、黄疸等症状显著好转,食欲上升或体重上升,战胜疾病信心提高;平均生存时间109.3天(17-320天),中位生存时间92天。结论对于不能手术的胆管癌栓,经皮介入治疗是一种可以选择的方法,能够改善病人的生存质量:Ⅳ型癌栓可以应用覆膜支架治疗,而Ⅲ型癌栓的治疗方案应根据病人的具体状况选择覆膜支架、永久性外引流或内引流;金属裸支架不宜在胆管癌栓的病例中应用。更多还原

【Abstract】 Malignancies of the biliary hilum have an extremely poor prognosis,with less than 10%of patients surviving 5 years after the diagnosis.This tumor is characterized by its deep spread into the liver along the periductal lymphatics and perineural spaces as well as along the bile duct wall.The resectability rates for high bile duct tumors are generally reported to be approximately 10%-20%,although rates as high as 96.5%, with 50.9%undergoing radical resection,have been reported.For the vast majority of patients,palliation is the goal.Although surgical bilioenteric bypass has been the traditional palliative approach,this therapy cannot be applied to all patients,and surgical mortality rates have been reported to be as high as 33%when extensive resections are required.Percutaneous palliation of biliary obstruction resulting from hilar malignancy can be accomplished in a variety of ways.Various self-expanding metallic stents with differing constructions have been available for the treatment of malignant biliary strictures.Although it is still controversial whether all segments of the liver should be drained,the concerns regarding unilateral drainage include the inability to relieve jaundice and the potential for bacterial contamination of an undrained segment,with the possibility for subsequent biliary sepsis and death. Bilateral percutaneous transhepatic biliary drainage(PTBD) has been performed with placement of multiple stents with unilateral or bilateral transhepatic approaches. Several techniques to drain the right and left hepatic ducts via a single percutaneous tract have been developed to eliminate the additional morbidity and discomfort associated with a second PTBD procedure. Part 1:Percutaneous Transcholecystic Biliary Metallic Stent Deployment:feasible study in the canine and the pathology of the stented bile duct.PURPOSEthe purpose of this study was to report our initial experiment with a canine model for biliary metal stent implantation through a percutaneous transcholecystic access.MATERIALS AND METHODSTen dogs,weighing 22.5-29.5kg,fasted for 24h then anesthesia.After computer tomography guidance,the canines’ gallbladders were punctured percutaneously under ultrasound.Omnipaque was given to opacity the gallbladder and extrahepatic biliary system.Using an Introducer Set and superstiff wire,a 5F sheath,with a length of 30 cm, was placed through the cystic duct into the common bile duct.Then mental stents were deployed into the common bile duct through cystic duct.Follow-up one month with CT scan and chemistry test.Autopsy was performed after one month to evaluate the safety and feasibility of this animal model.RESULTSPuncture of gallbladder was successful in all ten dogs Metallic stents were successfully deployed into eight dogs,while the other two were failure because of the sharp angulation of cystic duct and common bile duct.Seven animals tolerated the whole procedures(including deploying the metal stent) without changes in their clinical conditions and no symptoms.One died of bile leakage.At the 1-month follow-up,the hepatic function was within the normal range in four of the dogs.Alkaline phosphatase (AKP) increased from 5 to 10 days after operation in two of dogs and total bilirubin increased in one dog.These abnormalities recovered one month later.There was no obvious migration for all stents during the follow-up period,which was evaluated by CT scan.CONCLUSIONSThis technique allows a safe and feasible access into the biliary system using a percutaneous transcholecystic approach especially for a long-term interventional research.Part 2:The Clinical Study of Metallic Stents in the Treatment of Complex Hilar CholangiocarcinomaPURPOSETo evaluate the technical success and clinical efficacy of multi stents placement in the management of hilar cholangiocarcinoma.MATERIALS AND METHODS45 consecutive patients with hilar cholangiocarcinoma were treated with percutaneous transhepatic placement of two or three self-expandable metallic endoprostheses in a different configuration.These patients ranged in age from 39 to 79 years and included 27 men and 18 women.The cause of hilar obstructions in these patients are all cholangiocarcinoma included Bismuth classification wereⅡ(n=12),Ⅲa (n=17),Ⅲb(n=10),andⅣ(n=6).All patients were considered unsuitable candidates for surgical resection on the basis of medical fitness,tumor extent,or both,and endoscopic attempts to drain the right and left hepatic ducts had been unsuccessful in some patients.All PTBD procedures were performed with use of sonographic and fluoroscopic guidance by way of a left ventral or right lateral approach,or both.The stents used in this study were self-expanding nitinol stents(Antai Company,BEJING). All stents were placed 3-7 days after the initial drainage procedure.Then 2 or 3 stents were placed in the configuration of T,Y or X over the stricture.Three days after stent placement,contrast material was injected to confirm the position and patency of the endoprostheses,and external drainage catheters were removed in all patients.The study endpoints were followed at monthly intervals during the follow-up periods.Medical records were reviewed,ultrasonography(US) or computed tomography(CT) of the liver was performed,and serum bilirubin levels were checked.Technical success was defined as the deployment of the endoprostheses across the stricture with good radiologic positioning and bile passage down the stent.Successful decompression of the biliary system was defined by a decrease in serum bilirubin level more than 30% versus baseline value within the first week after stent insertion.In cases of recurrent jaundice,patients were evaluated by US,percutaneous transhepatic cholangiography, or CT.At the time of death,the stent was considered to be patent if the patient had a normal bilirubin level or stable mild hyperbilirubinemia.Complications were also evaluated with medical records and laboratory data.Statistical analysis was performed with use of SAS software(version 8.1) and SPSS(version 11.0).Stent patency rate and patient survival rate were calculated according to the Kaplan-Meier method.A Cox proportional-hazards model was used to assess differences affected by age,sex,or Bismuth type of obstruction.RESULTSStent placement with two or three endoprostheses was successful in all patients. Follow-up cholangiograms on the third day after stent placement showed that the system was adequately decompressed in all cases.All patients showed a significant decrease in serum bilirubin level.A paired t test of pre-and post procedural mean bilirubin levels showed a P value less than 05,which was considered statistically significant.All patients were free of external drainage tubes after the stent insertion. There were no major complications directly related to stent insertion.The usual complications of self-limiting hemobilia and cholangitis were associated with initial biliary drainage or dilation of the tract.No related to the procedure.The mortality rate within 30 days of stent placement was 2.2%(1 of 45).The mean survival and stent patency times were 215.3 days(range,26-516 days) and 181.5 days(range,26-473 days),respectively.There were no statistical differences in age,sex,or Bismuth type.CONCLUSIONSMulti stents placement is simple,safe,and reliable in achieving bilateral internal bile drainage in patients with complex hilar cholangiocarcinoma.Part 3:The Clinical Study of Percutaneous Intervention in the Treatment of Obstructive Jaundice due to Bile duct thrombosisPURPOSETo explore the Percutaneous Intervention in treatment of obstructive jaundice due to bile duct thrombosis in order to improve clinical efficacy and patients’ quality of life.MATERIALS AND METHODS27 patients with obstructive jaundice due to bile duct thrombosis,ranged in age from 32 to 82 years and included 22 men and 5 women,were caused by hepatic cellular cancer(19 cases),carcinoma of gallbladder(4 cases),rectal cancer(1 case) and gastric cancer(3 cases).It was proved by operative pathology for 16 patients,punture biopsy for 5 patients,bile duct biopsy forceps for 3 patients and combination of clinical, biochemistry and imaging for 3 patients.The bile duct thrombosis included Ueda classification were typeⅢfor 23 cases(85.2%) and 4 cases(14.8%).All patients were treated with percutaneous transhepatic biliary drainage. Permanent external drainage was prefered when the internal drainage associated with hemobilia and cholangitis.Stent placement was chosed if jaundice and other symptoms were improved.Internal drainage tube was remained accompanied with reccurence of symptoms.RESULTSPTBD was success in all cases.The procedures were preferd as below:Permanent external drainage for 5 patients,internal drainage and adjustment for 13 patients, covered stents for 7 patiens,stents placement with external drainage for 2 patients because of hemobilia and cholangitis who died 30 days later.Complications: immediate hemobilia due to puncturation for 7 cases(25.9%),hemobilia post-operation duration for 19 cases(70.4%),drainage tube falling off for 2 cases(7.4%).The conditions were sovled with corresponce treatment.Quality of life was considered to be improved for 23 patients(85.2%) Because symptoms of fever and jaundice was improved,better weight And appetite and self-confidence to fight against disease was elevated.The mean survival time and median survival time were 109.3 days(range, 17-320 days) and 92 days,respectively.CONCLUSIONSPercutaneous Intervention is one of choices to improve the patients’ quality of life in case of unresectable bile duct thrombosis.Covered stent was prefered with typeⅣthrombosis,choice of covered stent,external drainage and internal drainage for typeⅢadjusted correlated with different conditions,bare metalic stent was unsuitable for bile duct thrombosis.更多还原