肝细胞和脾细胞单独或联合输注对异种胰岛细胞移植排斥反应的影响

目的 探讨供者的肝细胞和脾细胞输注对同一供者胰岛细胞移植排斥反应的影响。方法 经尿静脉给BALB/c小鼠糖尿病模型注射供者（猪）的肝细胞和脾细胞，腹腔内注射途径进行猪胰岛细胞移植。移植后测定受者的血糖变化，观察小鼠移植物有功能存活时间。同时测定小鼠巨噬细胞吞噬功能，脾脏淋巴细胞转化功能和自然杀伤细胞活性的变化。结果 胰岛细胞移植前输注肝细胞，脾细胞以及肝细胞和脾细胞混合悬液者，移植物有功能存活时间延长，其淋巴细胞转化率。自然杀伤细胞活性及巨噬细胞的吞噬功能均较低，以肝细胞和脾细胞联合输注者为著。结论 移植前少量多次的供者肝细胞和脾细胞输注可以降低异种胰岛细胞移植排斥反应的强度。     

胰岛细胞移植的研究进展

糖尿病是一种严重危害人类身体健康和生活质量的全球性常见病,针对1型和部分2型糖尿病患者,胰岛移植将是比较彻底的治疗方法.本研究对包括胰岛细胞移植的分类,胰岛移植物的制备、保存及鉴定,移植部位的选择,免疫排斥机制,基因技术的应用及临床病例治疗技术等方面详细阐述了胰岛细胞移植目前的研究现状.随着分子生物学技术和相关学科迅速发展,细胞混合培养,转基因技术,β细胞株的建立,异源性胰岛细胞移植等一系列方法兴起,胰岛移植必将给彻底治愈1型糖尿病带来新的前景.     

免疫缺陷树突状细胞诱导异种胰岛细胞移植耐受

目的　研究受体来源免疫缺陷树突状细胞(dendriticcell, DC)诱导异种胰岛细胞移植的免疫耐受作用及其机制。方法　从BALB/C小鼠骨髓干细胞诱导分化免疫缺陷DC,负载Wistar大鼠MHC抗原。将上述DC通过尾静脉回输糖尿病小鼠体内(预处理组), 7d后分别将Wistar或SD大鼠胰岛细胞移植于受体鼠肾包膜下。观察移植物存活时间,检测T细胞增殖及TH1 /TH2细胞因子的表达。结果　与对照组相比,预处理组胰岛细胞存活时间明显延长(P < 0. 0 5 ),而以SD大鼠胰岛细胞作为供体的移植物存活时间无明显改变。免疫缺陷DC预处理受体鼠T细胞增殖反应微弱,且TH1 /TH2细胞因子表达明显下降。结论　负载异种MHC抗原的免疫缺陷型DC预处理受体可诱导抗原特异性T细胞无能,以及TH1 /TH2细胞因子的低表达,从而有效地延长异种胰岛细胞存活时间。     

胰岛细胞移植前预处理的研究进展

在移植前预先对移植胰岛细胞进行技术处理,可以降低免疫原性,增强胰岛细胞功能,从而使胰岛细胞移植真正成为有效控制血糖代谢、减少和改善糖尿病并发症、进而达到根治糖尿病的治疗手段。     

胰岛细胞移植的临床免疫问题

胰岛细胞移植是目前糖尿病治疗中的一个研究热点。国内外在实验和临床研究中均有不少成功的经验报道。本文就胰岛细胞移植在临床应用中所面临的免疫问题从免疫抑制方案的选择、免疫调节、诱导耐受以及免疫隔离策略等方面进行简要综述。     

微囊化胰岛细胞移植进展

本文综述了微囊化胰岛细胞移植近年的进展。     

胰岛细胞移植的研究进展

胰岛细胞移植治疗糖尿病存在两个障碍，组织来源不足和免疫排斥反应。分子生物学、组织工程学、免疫学、临床药理学等相关学科的发展为上述问题的解决提供了可能。本文就胰岛细胞移植研究的最新进展情况作一综述。     

兔胰岛细胞团颅内移植治疗糖尿病的研究

将新鲜制备的成年兔胰岛样细胞团经腰椎穿刺注入脊髓腔，采取小剂量多次颅内移植治疗糖尿病兔。术后不用免疫抑制剂，不用外源性胰岛素。结果１０只糖尿病兔在胰岛细胞团颅内移植后，３只显效，２只有效，无排斥反应及神经系统异常。     

胰岛移植基础研究

胰岛移植因为安全、有效而一直成为糖尿病治疗中的研究热点。近年来，随着基因工程技术、干细胞定向诱导分化技术的不断成熟，胰岛移植可能在今后数年内得以广泛开展，现对此作一简述。     

胰岛细胞移植前预处理的研究进展

在移植前预先对移植胰岛细胞进行技术处理，可以降低免疫原性，增强胰岛细胞功能，从而使胰岛细胞移植真正成为有效控制血糖代谢、减少和改善糖尿病并发症、进而达到根治糖尿病的治疗手段。     

Heart transplantation in patients with liver cirrhosis

OBJECTIVE: Liver cirrhosis is considered to be a contraindication to heart transplantation. However, the clinical outcome of heart transplantation in patients with liver cirrhosis has not been reported. Here, we sought to evaluate the clinical outcome of heart transplantation in cirrhotic patients. METHODS: Data were collected by retrospective chart review. Patients with liver cirrhosis at the time of transplantation were included. RESULTS: Between 1987 and 2007, 12 patients with liver cirrhosis underwent heart transplantation at the authors' hospital. Diagnosis of liver cirrhosis was based on preoperative abdominal sonography in five, autopsy in five, and laparotomy in two patients. Causes of heart failure were dilated cardiomyopathy in four, coronary artery disease in three, congenital heart disease in three and valvular heart disease in two patients. Causes of liver cirrhosis were alcoholism in two, cardiac in seven, and unknown in three patients. The Child classification was class A in three, class B in five and class C in four patients. Overall, the hospital mortality rate was 50% and major in-hospital complications occurred in nine patients (75%). Patients with non-cardiomyopathy diagnosis, previous sternotomy, and massive ascites had a high hospital mortality rate. The median follow-up duration was 33.5 months. There was no late death. Late post-transplant complications occurred in four patients and there was no event of liver dysfunction. All survivors were in Child class A at outpatient follow-up. CONCLUSIONS: Although there was high mortality and morbidity, patients with end-stage heart failure and liver cirrhosis can be considered for heart transplantation with careful case selection.     

Clinical significance of recurrent primary biliary cirrhosis after liver transplantation

Abstract  Primary biliary cirrhosis (PBC) represents a classic indication for orthotopic liver transplantation (OLT); as an autoimmune disease, however, the existence and incidence of recurrent PBC is a matter of significant controversy. Between September 1988 and September 1994 a total of 544 OLTs was performed at our institution. Forty-nine patients (40 female) with a median age of 50.5 years and previous surgery in 36.4 %, received a liver graft for PBC. The mean serum bi-lirubin level was 8.9 mg/dl (range 0.7–29.7). Immunosuppression was commenced as a cyclosporine A-based quadruple therapy or with FK 506 and prednisolone. Protocol liver biopsies were taken at defined intervals posttransplant. Two patients died due to Legionella pneumonia and hypoxic brain damage 2 and 8 weeks after OLT, resulting in an actuarial 5-year survival rate of 95 % with 47/49 patients being alive compared to 83.5 % of all other liver recipients. Evidence of recurrence of PBC, as defined by elevated chole-static parameters and histological features of PBC, was found in four patients, another five patients showed only histological signs. Recurrence of PBC, which might compromise the long-term outcome after OLT, was suspected in 4/47 patients (8.5 %). This evidence of recurrent PBC is in conflict with findings of other groups that did not report recurrent PBC. OLT is still the optimal therapy for advanced PBC, with an excellent prognosis.     

肝移植治疗肝内胆管结石和肝包虫病

目的探讨肝移植治疗合并胆汁性肝硬化的广泛肝内胆管结石和不能手术治疗的肝包虫病的效果。方法对2例广泛肝内胆管结石伴胆汁性肝硬化和4例不能手术切除的肝包虫病(泡球蚴病)患者施行原位肝移植，术后定期随访，评价疗效。结果2例胆管结石患者已存活2年多：4例肝包虫病患者，除1例术后3个月死于心力衰竭外，其余3例已分别存活9个月、15个月及2年；存活患者均恢复了正常生活和工作。结论肝移植可作为治疗广泛肝内胆管结石和不能手术治疗的肝包虫病的有效手段。     

肝硬化失代偿期并发意外肝癌患者的肝移植及其临床特点

目的探讨肝硬化失代偿期并发意外肝癌患者的肝移植效果及其临床特点。方法11例肝硬化失代偿期患者接受原位肝移植,在术后的病肝病理检查中意外发现癌灶(称之为"意外肝癌"),其原发病,8例为乙型肝炎后肝硬化,丙型肝炎后肝硬化、酒精性肝硬化和原发性硬化性胆管炎各1例。11例术后采用他克莫司、霉酚酸酯及甲泼尼龙预防排斥反应,3个月后撤除霉酚酸酯,6个月后撤除甲泼尼龙。病肝沿水平面作间隔1 cm连续平行切片,对于直径大于1 cm或有灰白色结节者,完整取材。结果11例中,术前仅4例(36.4%,4/11)的甲胎蛋白(AFP)水平超过正常值。除1例肿瘤为多发外,其余均为单发,肿瘤直径最大为2.0 cm,平均直径为1.18 cm;肿瘤TNM分期,Ⅰ期占72.7%,Ⅲ期占27.3%;存在微血管侵犯2例,包膜完整、无血管及淋巴侵犯2例;病理诊断为胆管细胞癌1例,肝细胞癌10例。术后随访12～50个月,1例因肿瘤复发于术后10个月死亡。结论意外肝癌的病理学特点为肿瘤分期早,多为单发,组织分化程度高,肝移植后的1年存活率与良性肝病患者肝移植类似,肿瘤复发率低。     

门静脉血栓对终末期肝硬化病人行肝移植手术的影响

目的探讨合并门静脉血栓(portal vein thrombosis,PVT)的终末期肝硬化病人行肝移植手术的处理方法及其疗效。方法回顾性分析2010年1月至2015年12月在中山大学附属第一医院器官移植中心接受肝移植手术的152例终末期肝硬化病人的临床资料。32例合并PVT的病人作为PVT组,其中Ⅰ级10例、Ⅱ级13例、Ⅲ级8例、Ⅳ级1例。其余120例无PVT的病人作为对照组。结果PV/T组术前脾切除史的比例明显高于对照组(46.8%比18.3%,P0.05),差异有统计学意义。PVT组较对照组明显延长无肝期时间[(72.5±25.3)min比(57.6±18.4)min,P0.05]和总手术时间[(622.4±183.5)min比(503.2±123.6)min],差异均有统计学意义。2组病人在术中出血量、ICU住院时间、术后并发症发生率、围手术期病死率、1年及3年生存率的比较上差异均无统计学意义(P0.05)。PVT组术后再栓塞率高于对照组(9.4%比1.7%,P0.05)。结论门静脉血栓一定程度上增加了终末期肝硬化病人肝移植手术的难度,Ⅰ~Ⅲ级PVT不影响病人的预后,仍可通过肝移植手术取得良好的疗效。Ⅳ级PVT肝移植手术的难度和风险会明显增加,应谨慎对待。     

Liver transplantation for small HCC in cirrhosis

Segmental liver resection is generally considered the treatment of choice for small HCC in cirrhotic livers. Although in selected patients with small encapsulated nodules and low alpha-fetoprotein levels long-term survival can be expected after resection [4], Western experience is still limited, and follow-up studies too short so that the data presently available cannot be considered satisfactory [3]. The true value of alcoholization as a possible alternative therapy in these patients is still to be ascertained. When using these treatment modalities, the major problem is the high tumour recurrence within the liver [1, 6]. Three main reasons could explain these clinical observations:

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肝移植治疗原发性胆汁性肝硬化的远期效果观察

目的 观察肝移植治疗原发性胆汁性肝硬化(PBC)的远期效果.方法 对15例接受了肝移植的终末期PBC患者进行长期随访,中位随访时间为70个月(38～86个月),记录并总结随访期间患者的相关资料,分析肝移植术后患者的预后、新发疾病以及术后远期存活率.结果 15例PBC患者共接受原位肝移植16例次,其中1例因原发性移植肝无功能进行了2次肝移植.术后患者均采用环孢素A(或他克莫司)+霉酚酸酯+激素的三联免疫抑制方案,部分患者使用了熊去氧胆酸.术后2周时,患者肝功能指标基本恢复正常,乏力、皮肤瘙痒及黄疸等症状缓解,患者的生存质量明显改善.术后有4例患者出现新发疾病(26.7%),1例为乙型肝炎病毒感染,2例为自身免疫性肝炎,1例为结肠癌,经治疗后2例好转,2例治疗无效死亡.肝移植术后,患者无PBC复发,1、2和5年的存活率分别为100%、100%和86.7%.结论 肝移植可提高终末期PBC患者的生存质量和存活率,但一些少见的新发疾病对患者的远期存活率影响较大.     

78例肝硬化患者肠道细菌易位及其相关性研究

目的了解肝硬化患者肠道细菌易位（BT）的发生率及其相关危险因素,分析BT与术后感染的关系。方法对77例肝移植和1例未行肝移植的肝硬化患者进行术中采样,取外周血、门脉血及肠系膜淋巴结（MLN）,分别进行需氧及厌氧培养,了解BT的发生率。结合术前、术后各种临床资料分析发生BT的危险因素及BT的临床意义。结果78例肝硬化患者中BT的发生率为10．3％（8／78）;细菌易位的部位以MLN为主,占5／8,发生BT的细菌主要是肠道G-兼性厌氧杆菌（55．6％）,其次为G^＋兼性厌氧球菌（22．2％）。BT组患者术前胆红素总量显著高于无BT组（P=0．022）;发生BT的患者其术后感染的风险是无BT患者的1．3倍。结论高胆红素血症是促发BT的独立危险因素,发生BT的肝移植患者术后感染的风险明显升高。     

A Pugh score of 8 adequately selects patients with parenchymal cirrhosis for liver transplantation

The aim of our study was to develop simple and highly effective scores to estimate prognosis at 1 year for patients with parenchymal cirrhosis and to define the optimum time for liver transplantation with the same degree of accuracy as the prognosis estimation for primary biliary cirrhosis. The prognostic value of 19 variables was studied retrospectively in 91 patients with parenchymal cirrhosis using multivariate analysis and logistic regression. The best prognostic index was obtained with two independent variables: ascites and aminopyrine breath test. Although the receiver operating characteristic (ROC) curve for these two variables was better than the ROC curve for Pugh score, the percentage of correct prediction was excellent for both indices: 92% and 87%, respectively. The critical cut-off value of the Pugh score was 8.8. The prognostic value of a Pugh score ≤ 8 or > 8 was confirmed in a prospective study of 145 cirrhotic patients with 78% correct prediction. During this period, 21 patients with parenchymal cirrhosis received transplants with a preoperative Pugh score of 9.5 ± 2.0 (mean ± SEM) and 60% 1- and 2-year survival. In conclusion in parenchymal cirrhosis, a Pugh score > 8 indicates a poor prognosis at 1 year. This is a simple, easy and highly effective tool to define the optimal time for liver transplantation in this category of patients.     

采用Swan-Ganz导管评价肝硬化患者肝移植术前心功能的状态

目的 采用Swan-Ganz导管评价肝硬化患者肝移植术前心功能的状态.方法 择期拟行原位肝移植术患者60例,年龄45～64岁,ASAⅡ-Ⅳ级,按术前肝功能状态分为2组:肝硬化代偿组(C组,n=28)和肝硬化失代偿组(H组,n=32).静脉注射咪达唑仑、异丙酚、维库溴铵和芬太尼麻醉诱导,气管插管后行机械通气,维持P_(ET)CO_2 30～45 mm Hg;吸入异氟醚,间断静脉注射芬太尼,静脉输注维库溴铵维持麻醉.常规监测HR,麻醉诱导后桡动脉穿刺置管,监测MAP;右侧颈内静脉置入Swan-Ganz漂浮导管,监测心输出量(CO)、心指数(CI)、右室射血分数(RVEF)、平均肺动脉压(MPAP)、肺动脉楔压(PAWP)、右房压(RAP)、右心室舒张末期容积(RVEDV)、右心室收缩末期容积(RVESV)和心搏指数(SVI),计算右室每搏功指数(RVSWI)、左室每搏功指数(LVSWI)、体循环血管阻力(SVR)和肺循环血管阻力(PVR).结果 与C组比较,H组HR、MAP、RAP和RVEF差异无统计学意义(P>0.05),CO、CI、SVI、MPAP、PAWP、RVEDV、RVESV、RVSWI和LVSWI升高,SVR和PVR降低(P<0.05).结论 原位肝移植术前肝硬化失代偿患者处于高排低阻状态,肺动脉压升高,心脏收缩功能和舒张功能降低,应加强心脏功能的保护.