肝移植术后肝动脉并发症的再次肝移植治疗

目的 探讨再次肝移植治疗肝移植术后肝动脉并发症的可行性及手术时机.方法 回顾性分析2003年12月至2006年12月收治的13例肝动脉并发症患者再次肝移植的临床资料.结果 再次肝移植的无肝期、手术时间和首次移植比较差异无统计学意义(P=0.291,P=0.312),术中出血量、ICU停留时间和首次移植比较差异有统计学意义[(3.1±1.1)L比(1.5±0.9)L(P=0.005),(4.3±1.8)d比(3.2±2.5)d(P=0.015)].围手术期病死率为38.5%(5/13),其中移植间隔1个月内死亡1例(1/4),超过1个月死亡4例(4/9).死亡原因分别为急性肾功能衰竭2例、严重感染2例、心肌梗死1例.8例存活,随访6～51个月,中位生存时间22.5个月.结论 再次肝移植是治疗肝移植术后肝动脉并发症导致不可逆性肝功能损害时的惟一有效手段.选择适宜的手术时机和手术方式、调整免疫抑制方案、加强围手术期管理是提高再次肝移植疗效的关键.     

肝癌肝移植生存情况及预后影响因素分析（附109例报告）

目的了解原发性肝细胞癌（肝癌）患者肝移植术后的生存情况,探讨影响其预后的危险因素。方法回顾性分析2004年1月至2007年12月中山大学附属第三医院肝移植中心的109例肝癌肝移植病例的临床资料。应用Kaplan-Meier法计算累积生存率和无瘤生存率,采用Log-rank检验和Cox回归模型分别进行无瘤生存率单因素、多因素分析。结果 109例肝癌肝移植患者中,37例肿瘤复发,占总数的33.9%,复发时间2～25（中位时间8）个月。全部病例1年、3年、5年累积生存率分别为86.9%、66.1%、56.6%,而1年、3年、5年无瘤生存率分别为78.3%、64.7%、53.1%。单因素分析显示,影响肝癌肝移植术后无瘤生存率的危险因素有肿瘤大小、肿瘤侵犯血管及病理分化程度。Cox风险回归模型多因素分析发现,肿瘤侵犯血管及病理分化程度是影响肝癌肝移植患者术后无瘤生存率的独立危险因素（均为P〈0.05）。结论影响肝癌肝移植患者术后无瘤生存率的独立危险因素是术前肿瘤侵犯血管和术后病理肿瘤分化程度,应严格筛选肝癌肝移植的适应证可有效降低术后肿瘤的复发率。     

线粒体在雷帕霉素诱导肝癌细胞Bel-7402凋亡中的作用

目的观察雷帕霉素（rapamycin,RAPA）体外对肝癌细胞Bel-7402的生长抑制和诱导凋亡作用,并探讨线粒体在诱导凋亡机理中的作用。方法以5、10、20、30、40和50nmol／L不同浓度的RAPA作用于体外培养的Bel-7402细胞,MTT法检测细胞生长抑制率;应用流式细胞仪检测细胞凋亡;Hoechst 33258荧光染色法观察细胞凋亡时的形态学变化;JC-1染色法检测细胞线粒体膜电位（mitochondrial membrane potential）的变化。结果RAPA可显著地抑制Bel-7402的生长,诱导细胞发生凋亡,并呈现出明显的量-效与时-效关系,50nmol／LRAPA作用72h,引起的细胞抑制率和凋亡率明显高于其他浓度药物组（P〈0．01）。RAPA作用Bel-7402细胞48h后,在Hoechst33258荧光染色图片上可见细胞核浓缩、细胞核碎裂等典型的细胞凋亡特征。凋亡过程中线粒体膜电位下降。结论RAPA能抑制Bel-7402细胞的生长,诱导细胞凋亡发生,线粒体膜电位下降在凋亡过程中可能起到重要作用。     

创伤后早期肠内营养

早期肠内营养(EN)在创伤后的应用非常重要,它有诸多益处,例如减少感染并发症的发生,缩短ICU入住时间及机械通气时间等。该文的目的在于强调创伤后早期肠内营养的应用。为什么要应用EN?尽管肠外营养(PN)通常被首先考虑,但相比之下,EN更符合生理、更便宜、更容易实施及维持,并能更好地补足营养和保护脏器功能。EN还可防止肠道菌群及毒素易位进入循环,从而减少细胞因子的产生,减弱全身炎症反应。给予什么EN?针对创伤给予免疫增强饮食(包含谷氨酰胺、ω-3脂肪酸),可减少脓毒血症的发生。何时给予EN?EN不需要以肠蠕动恢复为起始依据。EN…     

原位肝移植治疗终末期自身免疫性肝病

目的 评价肝移植治疗终末期自身免疫性肝病的疗效并总结临床经验.方法 回顾性分析2003年9月至2009年7月间因终末期自身免疫性肝病接受肝移植手术的11例患者的临床资料,其中8例为原发性胆汁性肝硬化,2例为自身免疫性肝炎,1例为原发性硬化性胆管炎.平均年龄为(44.2±8.7)岁.手术方式均采用附加腔静脉整形的改良背驮式肝移植术.术后免疫抑制治疗采用他克莫司或环孢素A联合激素的二联免疫抑制方案,部分患者使用骁悉和熊去氧胆酸.结果 本组11例患者中2例原发性胆汁性肝硬化患者死亡,其中1例于术后第5天死于肺部感染和多器官功能衰竭,另1例于术后964 d死于脓毒症和移植肝失功.5例患者术后1个月内出现急性排斥反应,加强免疫抑制治疗后痊愈.9例患者生存良好并存活至今,随访期7～62个月,中位随访时间为38个月.受体1年存活率为91%,3年存活率为82%,最长存活期5年.随访期间未发现复发病例.结论 肝移植是治疗终末期自身免疫性肝病的惟一有效手段,手术时机的正确把握和有效的免疫抑制治疗是减少肝移植术后并发症的关键.

Abstract：

Objective To evaluate the effect of liver transplantation for end-stage autoimmune liver disease (ESALD) and summarize the clinical experience of liver transplantation in the treatment of ESALD.Methods The clinical data of 11 ESALD cases who underwent liver transplantation from September 2003 to July 2009 were analyzed retrospectively. There were 2 males and 9 females ( median age, 44. 2 ± 8. 7years). The indication of liver transplantation was end stage of primary biliary cirrhrosis (8 cases),autoimmune hepatitis (2 cases), and primary sclerosing cholangitis ( 1 case). In all cases, modified piggyback liver transplantation with venacavaplasty was carried out. Postoperatively all patients were treated with immunosuppressive agents including tacrolimus (or cyclosporine A) and prednisone, some patients were treated additionally with mycophenolate mofetil and ursodeoxycholic acid. Results Postoperatively 2patients of primary biliary cirrhosis died, one of lung infection and multiple organ failure on the 5th postoperative day, the other dying of sepsis and graft dysfunction on the 964th postoperative day. Five cases suffered from episodes of acute cellular rejection within 1 month after transplantation and was successfully reversed by strengthened immunosuppressive therapy. Nine patients recovered satisfactorily and with excellent life quality until now. Patients were followed up from 7 months to 62 months with the median follow-up time of 38 months. The recipient survival rate at 1 year and 3 years was 91% and 82% ,respectively. One patient has now survived for 5 years. No recurrent ALD case was found during follow up.Conclusions Orthotopic liver transplantation is an exclusive treatment for ESALD. Optimum operation timing and effective immunosuppressive treatment are very important for decreasing occurrence of complications.     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

影响良性终末期肝病肝移植术后远期死亡的预后因素分析

目的: 分析良性终末期肝病肝移植患者术后中远期的生存情况和导致中远期生存率下降的预后因素。 方法: 回顾性地分析2003年10月至2008年6月在我院行原位肝移植手术,且术后存活超过1年的221个良性终末期肝病受者的资料,选取包括受者术前变量、供者变量、术中变量和受者术后变量共27个可能影响患者长期存活的危险因素,采用Cox回归分析,筛选出影响肝移植受者长期存活的独立危险因素。 结果: 221个受体中有28人在术后1年后死亡,主要死亡原因和相关死亡率为：感染、胆道并发症、HBV复发/再感染。保留在Cox回归方程内的协变量为：高龄、ABO血型、冷缺血时间、术后感染部位和胆道并发症。 结论: 良性终末期肝病的移植患者的中远期死亡原因主要是感染、胆道并发症和HBV复发/再感染。影响受者术后中远期存活的危险因素包括高龄（≥60y）,ABO血型（血型不符）,冷缺血时间（＞12h）,术后感染部位（肺部感染）和胆道并发症（移植肝胆管弥漫性狭窄）。术前严格筛选高龄患者,选择ABO血型相同或相符的供者,缩短冷缺血时间,积极防治术后感染和胆道并发症,将有助于提高受者术后中远期存活。     

西罗莫司对肝移植术后肾功能和血脂的影响

目的探讨原发性肝细胞癌（肝癌）肝移植患者术后使用西罗莫司（sirolimus）对肾功能和血脂的影响。方法 56例肝癌肝移植患者分为两组。研究组（33例）采用西罗莫司＋小剂量他克莫司（FK506）＋肾上腺皮质激素（激素）方案,对照组（23例）采用FK506＋激素方案。动态监测两组患者术前,术后1、3、6、9、12个月的血清肌酐（Scr）、血清总胆固醇、甘油三酯及高密度脂蛋白的变化情况,分别行组内不同时点比较和同时点组间比较。结果术前两组患者的Scr水平差异无统计学意义（P〉0.05）,术后9个月时的Scr比较差异有统计学意义（P〈0.05）,研究组的Scr水平低于对照组,且研究组术后Scr呈先升高再降低的变化趋势,对照组Scr呈缓慢上升的趋势。术前两组患者的血脂水平相当（P〉0.05）。两组患者术后1个月的甘油三酯水平,术后6个月时的总胆固醇水平和高密度脂蛋白水平比较差异有统计学意义（P〈0.05）,研究组均高于对照组。两组患者未发现与高脂血症相关的心脑血管疾病。结论西罗莫司是一种低肾毒性的免疫抑制剂,与小剂量的FK506合用时可以减少FK506的肾毒性。西罗莫司的主要的不良反应是高脂血症。     

肝移植术后外周血高迁移率蛋白B1的变化及其与早期脓毒症的关系

目的研究因肝衰竭行肝移植患者围术期外周血高迁移率蛋白1(high mobility group box-1 protein,HMGB1)的动态变化,探讨其与早期脓毒症的关系。方法前瞻性选取2008年10月—2009年7月因肝衰竭行肝移植手术患者17例作为研究对象,采用荧光定量RT-PCR方法检测手术开始前30 min,术后第1,3,7,14 d 5个时间点外周血HMGB1 mRNA。根据术后早期(14 d内)是否发生脓毒症分成脓毒症组和非脓毒症组,比较两组患者HMGB1 mRNA的动态变化和差异。结果 17例患者中男14例,女3例,年龄31～65岁,平均(45.3±9.0)岁。8例患者术后早期发生脓毒症,脓毒症诊断平均时间为5.5 d(4～10 d)。非脓毒症组术后第1天HMGB1 mRNA表达水平较术前显著升高[(3.50±1.20)vs.(1.80±0.59),P=0.036],第3天达到高峰(7.85±3.00,P0.001),然后逐渐下降,第14天回复至术前水平(2.62±1.11,P=0.301)。脓毒症组术后第1天HMGB1 mRNA表达水平较术前显著上升[(7.31±2.27)vs.(1.92±0.64),P=0.002],并一直维持在较高水平,第14天仍高于术前(12.45±5.58,P0.001)。脓毒症组术后各时间点HMGB1 mRNA均高于非脓毒症组(P0.001)。结论动态监测HMGB1的表达水平有助于预测肝移植术后早期脓毒症的发生。