小肠移植新时期：成就与挑战并存

全肠外营养是肠衰竭的重要治疗方法，但是长期肠外营养会出现一系列严重并发症，严重威胁患者的生存。小肠移植为肠衰竭患者提供了新的治疗手段，不仅使患者恢复临床自主营养，同时避免发生肠外营养相关并发症。近年来，小肠移植免疫抑制剂不断发展应用，同时手术技术和术后管理取得明显进步，使患者术后短期生存率明显提高，小肠移植已成为肠衰竭患者的标准治疗方法。但小肠移植仍面临诸多挑战：免疫排斥反应的诊治、感染的防治、术后营养支持等仍是亟待解决的问题，严重影响患者长期预后。     

肝小肠联合移植的术式探讨及术后处理一例

目的 总结1例保持门静脉连续性的小肠双造口方式肝小肠联合移植病例的手术操作和术后处理的经验.方法 受者为短肠综合征合并肝功能不良的男性患者,供者为尸体供者.联合切取器官,确保供者肠系膜上静脉和门静脉的连续性.移植肝静脉采用背驼式吻合,受者自体门静脉和供肝门静脉端侧吻合,胆道端端吻合,供者肝动脉和肠系膜上动脉吻合于受者腹主动脉;移植小肠约2 m,两端双造口于腹壁,未作肠道吻合.采用人源化抗CD52单克隆抗体诱导治疗,维持期单用他克莫司.行内镜下黏膜活检监测排斥反应.结果 术后1个月内,患者发生腹腔感染和疑似排斥反应各1次,分别经过手术和甲泼尼龙冲击治疗后痊愈.随访6个月,受者移植肝和小肠功能恢复良好,但仍有腹泻,需补充静脉营养,体重尚未完全恢复.结论 保持门静脉连续性的小肠双造口方式肝小肠联合移植可以简化手术操作,发生外科并发症的风险小,有利于肝脏和小肠功能恢复及术后排斥反应的监测,但是消化液未能进入移植小肠,也影响了受者的恢复.     

同种异体非整块肝脏-小肠联合移植

目的 报告国内首例同种异体非整块肝肠联合移植,重点讨论外科技术,并与整块肝肠联合移植技术进行比较。方法 患者因短肠综合征和全肠外营养(TPN)肝病接受非整块肝肠联合移植,植入小肠380cm。肠系膜上动脉、门静脉分别与受体腹主动脉、下腔静脉端侧吻合;供肝行改良背驮式肝移植。供体热缺血时间为2min 30s,移植肠冷缺血6h 40min,移植肝冷缺血8h 7min．术后免疫抑制方案采用FK506 激素 骁悉 赛尼哌。结果 患者恢复顺利,未发生排斥反应,至今仍存活,已恢复完全肠道营养。结论 非整块肝肠联合移植技术适合于成年受体、特别是既往曾有腹腔感染或接受多次腹部手术的患者。     

大鼠肝小肠联合移植肠壁酶活性变化的研究

目的探讨肝小肠联合移植后肠壁酶活性的变化及其与移植肠功能和免疫排斥反应之间的关系。方法用封闭群大鼠建立肝小肠联合移植模型,术后定期对移植组织进行病理学、酶组织化学检查。结果单独小肠移植组术后均发生排斥反应,肠壁酶活性消失。肝小肠联合移植组５６％可避免排斥反应,肠壁酶活性和神经成分得以保持和恢复。结论肝小肠联合移植可使供肠避免或推迟被排斥。术后检测肠壁酶活性和神经成分的变化可用于监测排斥反应     

非整块肝脏和小肠联合移植的外科技术(附一例报告)

目的　介绍国内首例非整块肝脏和小肠联合移植的外科技术。方法　采用在体灌注、整块切取的方法获取肝脏和小肠,供者器官采用 UW液保存。将供者肝脏、小肠联合植入短肠综合征合并胆汁淤积的男性受者体内,供肝采用改良背驮式肝移植术;供肠的动脉、静脉分别与受者的肾下腹主动脉和下腔静脉吻合。结果　至术后2个月时,移植小肠和肝脏均无排斥反应,肠黏膜结构正常,对肠内营养耐受良好;CT示移植肝形态正常,复查肝功能完全恢复正常。结论　选择性应用非整块肝脏和小肠联合移植术是安全有效的,特别适合需要接受肝脏、小肠联合移植的成年患者。     

临床同种活体部分小肠移植：附1例报告

目的：探讨临床同种活体小肠移植治疗短肠综合征的效果。方法：对1例因小肠扭转而切除大部分小肠和右半结肠，残留小肠仅20cm的超短肠综合征男性患者，行亲属活体同种部分小肠移植。供体为患者之母。受体术前行供体特异性输血，50mL/周，共8周。供受体巨细胞病毒感染状态均为阴性。移植肠长约160cm。移植肠的回结肠动静脉分别与受体肾下腹主动脉和下腔静脉端侧吻合，移植肠末端造口。术后给予抗排斥、抗感染、抗凝及营养支持治疗。结果：供体术后恢复顺利，无并发症。受体已健康存活31周，无感染和排斥反应。术后8周脱离肠外营养治疗，口服低脂饮食，D－木糖吸收试验结果接近正常。结论：同种活体部分小肠移植是治疗短肠综合征的有效措施。     

同种异体小肠移植的实验研究与临床应用报告

作者以杂交长白猪为模型，进行了同种异体小肠移植的系列研究．结果表明：①小剂量环抱素加雷公藤具有满意的抑制急性排斥反应的效果．②单用雷公藤能预防慢性排斥反应的发生．③移植肠的吸收功能在术后２周内明显下降，于术后４周，按氨基酸、葡萄糖与脂肪的顺序逐渐恢复．基于试验的结果，于１９９４年３月为一女病人施行了全小肠移植，术后恢复良好．本文讨论了小肠移植的实用性、免疫抑制剂的应用与促进移植肠功能恢复等问题．     

肝小肠联合移植

肠功能衰竭患者长期依赖全肠外营养（totalparenteralnutrition，TPN）维持生存，一部分患者可因TPN发生肝功能障碍，甚至肝功能衰竭，如果这部分患者继续应用TPN维持生命，他们的平均生存时间只有6—12个月。肝小肠联合移植成为挽救这部分患者生命的治疗措施。     

母子亲体小肠移植治疗小肠衰竭的方法及疗效探讨：附1例报告

目的：探讨母子亲体小肠移植的方法及其对短肠综合征所致小肠衰竭的疗效。方法：为1名15岁短肠综合征（仅残留小肠8cm）致小肠衰竭的男患者行小肠移植术。供体为患者母亲。取供体带血管蒂回肠中下段1.2m移植于受体腹腔，两端分别造瘘及作人工肛。二期手术于6个月后施行，将受体残余肠中部横断，上下端分别与供肠近、远段行端侧吻合。结果：供、受体手术顺利。受体一期手术后曾发生感染及排斥，经治疗后痊愈。二次术后随访8个月，受体小肠功能逐渐恢复，患者体重明显增加，一般情况好，进食半流质，生活能自理。结论：亲体小肠移植是治疗短肠综合征肠衰竭的有效方法。排斥和感染是威胁小肠移植安全的主要因素。     

同种异体不肠移植的实验研究与临床应用报告

作者以杂交长白猪为模型，进行了同种异体小肠移植的系列研究。结果表明：①小剂量环孢素加雷公藤具有满意的抑制急性排斥反应的效果。②单用雷公藤能预防慢性排斥反应的发生。③移植肠的吸收功能在术后２周内明显下降，于术后４周，按氨基酸，葡萄糖与脂肪的顺序逐渐恢复。基于试验的结果，于１９９４年３月为一女病人施行了全小肠移植，术后恢复良好。本文讨论了小肠移植的实用性，免疫抑制剂的应用与促进移植肠功能恢复等问题。     

Intestinal and multivisceral transplantation

Intestinal and multivisceral transplantation represents an important treatment option for patients with intestinal failure. Early attempts were hindered by technical and immunological complications. However, significant developments in immunosuppressive therapy have led to marked improvements in outcomes in recent years. The main indications for intestinal transplantation are life-threatening complications or unacceptable quality of life on total parenteral nutrition (TPN), or following evisceration for extensive intra-abdominal tumours. In suitable patients, in the absence of significant liver disease, an isolated intestinal graft is appropriate. A combined liver and intestinal transplant is indicated in patients with significant liver disease, almost always as a result of long-term TPN. Pathology affecting the foregut may require more extensive grafts including the stomach, duodenum and pancreas. Multivisceral transplantation is technically demanding. The transplant recipient has frequently undergone multiple previous laparotomies and may present with multiple stomata, fistulae, collections, distortion of intra-abdominal anatomy and significant contraction of the abdominal cavity. The most important early complications are acute rejection and sepsis, which frequently occur together. In the long-term, chronic rejection and malignancy are the leading causes of graft loss and mortality. It is hoped that ongoing improvements in intestinal and multivisceral transplantation may eventually justify its use as a primary alternative to long-term TPN.     

Intestinal and multivisceral transplantation

Intestinal and multivisceral transplantation represents an important treatment option for patients with intestinal failure. Early attempts were hindered by technical and immunological complications. However, significant developments in immunosuppressive therapy have led to marked improvements in outcomes in recent years. The main indications for intestinal transplantation are life-threatening complications or unacceptable quality of life on total parenteral nutrition (TPN), or following evisceration for extensive intra-abdominal tumours. In suitable patients, in the absence of significant liver disease, an isolated intestinal graft is appropriate. A combined liver and intestinal transplant is indicated in patients with significant liver disease, almost always as a result of long-term TPN. Pathology affecting the foregut may require more extensive grafts, including the stomach, duodenum and pancreas. Multivisceral transplantation is technically demanding. The transplant recipient has frequently undergone multiple previous laparotomies and may present with multiple stomata, fistulae, collections, distortion of intra-abdominal anatomy and significant contraction of the abdominal cavity. The most important early complications are acute rejection and sepsis, which frequently occur together. In the long term, chronic rejection and malignancy are the leading causes of graft loss and mortality and immunosuppression related renal impairment a major source of morbidity. It is hoped that ongoing improvements in intestinal and multivisceral transplantation may eventually justify its use as a primary alternative to long-term TPN.     

Intestinal and multivisceral transplantation

Intestinal and multivisceral transplantation represents an important treatment option for patients with intestinal failure. Early attempts were hindered by technical and immunological complications. However, significant developments in immunosuppressive therapy have led to marked improvements in outcomes in recent years. The main indications for intestinal transplantation are life-threatening complications or unacceptable quality of life on total parenteral nutrition (TPN), or following evisceration for extensive intra-abdominal tumours. In suitable patients, in the absence of significant liver disease, an isolated intestinal graft is appropriate. A combined liver and intestinal transplant is indicated in patients with significant liver disease, almost always as a result of long-term TPN. Pathology affecting the foregut may require more extensive grafts including the stomach, duodenum and pancreas. Multivisceral transplantation is technically demanding. The transplant recipient has frequently undergone multiple previous laparotomies and may present with multiple stomata, fistulae, collections, distortion of intra-abdominal anatomy and significant contraction of the abdominal cavity. The most important early complications are acute rejection and sepsis, which frequently occur together. In the long-term, chronic rejection and malignancy are the leading causes of graft loss and mortality and immunosuppression related renal impairment a major source of morbidity. It is hoped that ongoing improvements in intestinal and multivisceral transplantation may eventually justify its use as a primary alternative to long-term TPN.     

肝、肾联合移植12例报告

目的 对肝、肾联合移植的临床情况进行总结。方法 为12例肝、肾功能异常患者施行肝、肾联合移植，采用多器官联合切取术整块切取供者器官。8例行经典式肝移植，4例行背驮式肝移植，均未行体外静脉转流；肾移植为常规术式。术前进行抗CD25单克隆抗体和抗胸腺细胞球蛋白诱导治疗，术后应用他克莫司（FK506）、霉酚酸酯及泼尼松预防排斥反应。结果 12例手术均获成功，移植肝及肾功能恢复良好。术后的并发症有移植肝急性排斥反应、FK506中毒、消化道出血、腹腔出血、肺部感染、腹腔感染（各1例次），所有患者均未发生移植肾急性排斥反应。结论 肝、肾联合移植是治疗终末期肝病合并肾功能衰竭的理想选择。     

猪肝肠联合移植免疫耐受的实验研究

目的 研究猪肝肠联合移植中肝移植物对同源小肠移植物免疫耐受的作用.方法 70头杂交长白猪分为4组,A、B、C组为辅助性同种异体肝肠联合移植(每组20头);D组为节段性间种异体小肠移植(10头).移植后A、D组未用免疫抑制剂治疗,B、C组分别采用常规剂量和小剂量的环孢素和甲基强的松龙治疗.结果 A组术后小肠移植物较D组排斥反应时间延迟,程度明显减轻(P＜0.05).常规剂量的B组与小剂量的C组在术后存活时间、排斥反应开始时间以及排斥反应程度方面差异无统计学意义(P＞0.05).结论 猪同种异体肝肠联合移植中肝移植物可以诱导同源小肠移植物免疫耐受.     

接受同一供体肝肾联合移植与肾移植的临床研究

目的探讨肝肾联合移植肝脏对肾脏的保护作用。方法我院移植中心2002年5月至2006年9月间共进行8例肝肾联合移植手术，对此8例患者及接受同一供体对侧供肾8例肾移植患者及移植物存活率、排斥反应发生率进行分析。结果肝肾联合移植患者及移植物存活率为100％，无可证实排斥反应发生。术后8例患者移植肝功能迅速恢复正常，7例移植肾功能迅速恢复正常，1例移植肾发生急性肾小管坏死，于术后第52天肾功能恢复正常。对应8例单纯肾移植患者，发生急性排斥反应1例，予甲基强的松龙冲击治疗及应用抗人T淋巴细胞免疫球蛋白（anti-thymocyte globulin，ATG）后，于术后50d移植肾功能恢复正常，余7例患者恢复良好，至末次随访肾功能均正常。结论肝肾联合移植肝脏对肾脏有一定的保护作用。     

排斥反应时血清可溶性白细胞相关免疫球蛋白样受体1的水平及意义

目的 探讨可溶性白细胞相关免疫球蛋白样受体1(sLAIR-1)与移植物排斥反应的相关性.方法 采用双抗体夹心酶联免疫吸附试验测定23例肝移植、139例肾移植患者的血清sLAIR-1水平,并以健康志愿者为对照.结果 健康志愿者的血清sLAIR-1水平为(4.3±2.3)μg/L,移植器官功能正常者(肝移植11例,肾移植87例)的sLAIR-1为(6.3±3.7)μg/L,二者比较,差异无统计学意义(P>0.05).肝移植后发生急性排斥反应的6例患者,其血清sLAIR-1水平为(47.2±25.9)μg/L;肾移植后后发生急性排斥反应的20例患者,其血清sLAIR-1水平(36.3±14.7)μg/L;移植肾功能丧失的5例患者,其血清sLAIR-1水平为(28.8±9.4)μg/L,上述三者的血清sLAIR-1水平均明显高于移植物功能正常者和健康志愿者(P<0.01).移植肝重度排斥反应的1例,其血清sLAIR-1高达117.3μg/L,为正常人的27倍.移植肝慢性排斥反应者(5例)和移植肾慢性排斥反应者(27例)的血清sLAIR-1水平分别为(16.1±6.4)μg/L和(13.1±5.5)μg/L,也明显高于移植物功能正常者和健康志愿者(P<0.05).结论 发生排斥反应者的血清sLAIR-1水平升高,其水平的升高可能是发生排斥反应的重要风险因素.     

肝肾联合移植15例报道

目的探讨肝肾联合移植的适应证和疗效。方法对2001年2月至2003年12月施行肝肾联合移植术的15例患者进行了随访。15例中,乙型肝炎后肝硬化合并肝肾综合征8例、合并尿毒症2例、合并糖尿病肾病1例;多囊肝和多囊肾2例;Caroli病合并多囊肾1例;酒精性肝硬化合并尿毒症1例。对肝肾联合移植患者的手术方式,围手术期并发症,术后急、慢性排斥反应和乙型肝炎复发情况及随访结果进行了分析。结果15例肝肾联合移植术后移植物功能均恢复良好,6个月和1年生存率为100%。1例术前有严重营养不良者,术后给与48d的呼吸机支持后康复。术后创面出血和消化道出血各1例,经非手术治疗后治愈。胆道吻合口狭窄1例,用内镜下球囊扩张术治愈。1例术后2周发生急性移植肝排斥反应,给予激素冲击治疗后得到控制。1例术后30个月时因停用拉米夫定后乙型肝炎复发死于移植肝功能丧失。结论肝肾联合移植是终末期肝病合并慢性肾功能衰竭或肾功能损害的安全有效方法。对乙型肝炎患者术后尽早应用拉米夫定和乙型肝炎病毒免疫球蛋白预防肝炎复发。     

Cadaveric small bowel/split liver transplantation in a child

Scarcity of size-matched grafts continues to be a major limiting factor for liver and combined liver/intestinal transplants in the pediatric population. It is reported that 29 % of pediatric patients listed for hepatic transplantation die while waiting for a donor. The reported mortality of pediatric patients awaiting intestinal transplantation is about 40 %. We report on a technique of segmental liver and intestinal transplantation in a child. To our knowledge, this is the first report of a combined split liver-intestinal transplantation. We used a cadaveric donor, but the technique can also be performed with a live donor. The adult recipient of one segment of the liver was discharged home without complications. The child who received the combined liver intestinal graft developed intestinal perforation and severe rejection and died. If this technique is applied successfully, the adverse effects and mortality of a long pretransplant waiting period in pediatric patients may be avoided. Received: 7 May 1998 Received after revision: 29 September 1998 Accepted: 12 October 1998     

Ninety-five cases of intestinal transplantation at the university of Miami

Intestinal failure requiring total parenteral nutrition (TPN) is associated with significant morbidity and mortality. Intestinal transplantation can be a lifesaving option for patients with intestinal failure who develop serious TPN-related complications. The aim of this study was to evaluate survival, surgical technique, and patient care in patients treated with intestinal transplantation. We reviewed data collected from 95 consecutive intestinal transplants performed between December 1994 and November 2000 at the University of Miami. Fifty-four of the patients undergoing intestinal transplantation were children and 41 were adults. The series includes 49 male and 46 female patients. The causes of intestinal failure included mesenteric venous thrombosis (n = 12), necrotizing enterocolitis (n = 11), gastroschisis (n = 11), midgut volvulus (n = 9), desmoid tumor (n = 8), intestinal atresia (n = 6), trauma (n = 5), Hirschsprung’s disease (n = 5), Crohn’s disease (n = 5), intestinal pseudoobstruction (n = 4), and others (n = 19). The procedures performed included 27 isolated intestine transplants, 28 combined liver and intestine transplants, and 40 multivisceral transplants. Since 1998, we have been using daclizumab (Zenepax) for induction of immunosuppression and zoom videoendoscopy for graft surveillance. We began to use intense cytomegalovirus prophylaxis and systemic drainage of the portal vein. The 1-year patient survival rates for isolated intestinal, liver and intestinal, and multivisceral transplantations were 75%, 40%, and 48%, respectively. Since 1998, the 1-year patient and graft survival rates for isolated intestinal transplants have been 84% and 72%, respectively. The causes of death were as follows: sepsis after rejection (n = 14), respiratory failure (n = 8), sepsis (n = 6), multiple organ failure (n = 4), arterial graft infection (n = 3), aspergillosis (n = 2), post-transplantation lymphoproliferative disease (n = 2), intracranial hemorrhage (n = 2), and fungemia, chronic rejection, graft vs. host disease, necrotizing enterocolitis, pancreatitis, pulmonary embolism, and viral encephalitis (n = 1 case of each). Intestinal transplantation can be a lifesaving alternative for patients with intestinal failure. The prognosis after intestinal transplantation is better when it is performed before the onset of liver failure. Rejection monitoring with zoom videoendoscopy and new immunosuppressive therapy with sirolimus, daclizumab, and campath-1H have contributed to the improvement in patient survival. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001 (oral presentation).