肝移植治疗乙型肝炎、肝硬化并发肝癌的分析

目的 研究乙型肝炎、肝硬化并发肝癌行肝移植手术时机的选择及术后免疫抑制剂的应用.方法 对9例患者施行肝移植,其中4例为经典式原位肝移植,5例为背驮式原位肝移植,术后应用免疫抑制剂甲基泼尼松龙、他克莫司及吗替麦考酚酯(商品名:骁悉),同时采用抗乙型肝炎免疫球蛋白及拉米夫定预防乙肝病毒复发.结果 9例肝癌肝移植手术均获成功,2例术前情况差的患者术后死于多器官衰竭,1例死于急性排斥反应,余6例全部生存至今.结论 乙型肝炎、肝硬化并发肝癌最有效的治疗方法之一是肝移植,手术在肝癌转移前进行疗效较好,术后应用免疫抑制剂甲基泼尼松龙、他克莫司及吗替麦考酚酯可以有效控制免疫排斥的发生.     

肝移植治疗乙型肝炎、肝硬化并发肝癌的分析

 目的　研究乙型肝炎、肝硬化并发肝癌行肝移植手术时机的选择及术后免疫抑制剂的应用。方法　对9例患者施行肝移植,其中4例为经典式原位肝移植,5例为背驮式原位肝移植,术后应用免疫抑制剂甲基泼尼松龙、他克莫司及吗替麦考酚酯（商品名：骁悉）,同时采用抗乙型肝炎免疫球蛋白及拉米夫定预防乙肝病毒复发。结果　9例肝癌肝移植手术均获成功,2例术前情况差的患者术后死于多器官衰竭,1例死于急性排斥反应,余6例全部生存至今。结论　乙型肝炎、肝硬化并发肝癌最有效的治疗方法之一是肝移植,手术在肝癌转移前进行疗效较好,术后应用免疫抑制剂甲基泼尼松龙、他克莫司及吗替麦考酚酯可以有效控制免疫排斥的发生。     

肝癌肝移植术后停用免疫抑制剂1例报告

肝移植术后一般常规使用免疫抑制剂抗排斥治疗,我院1例原发性肝癌患者肝移植术后停用免疫抑制剂达9个月,未出现排斥反应,现总结报告如下。1病例报告患者,男性,因肝癌肝移植术后2年余于2011年9月20日收治我院。2009年3月28日因右上腹隐痛查腹部CT提示原发性肝癌,同年5月4日于外院行全肝切除加亲体右半肝移植术。术后采用他克莫司、霉酚酸酯片(MMF)、甲基强的松龙三     

肝移植术后并发肺癌1例

患者,60岁,因诊断“原发性肝癌、肝硬化、乙型病毒性肝炎”,在我院普外科2005年11月4日行“原位同种异体肝移植术”,手术顺利,病理报告:肝细胞肝癌(中分化)。术后一直服用他克莫司免疫抑制治疗,2006年6月14日出现咳嗽,以刺激性干咳为主,晨起有少量白粘痰,无其他不适主诉,自服抗     

肝癌肝移植16例体会

目的:总结肝癌肝移植的临床经验,探讨原位肝移植治疗原发性肝癌的疗效.方法:回顾分析2004年7月至2006年4月16例原发性肝癌肝移植的临床资料,均采用同种异体(尸体供肝)原位全肝移植,其中7例符合Milan标准,9例符合UCSF标准.结果:16例手术全部成功,围手术期死亡2例,随访2个月-24个月,死亡2例,1例术后3个月死于胆道铸型综合征、胆道感染,1例术后6个月死于胸腰椎转移、肺转移癌,现存活12例,1例带瘤生存.结论:肝移植是原发性肝癌的有效治疗手段,应严格掌握适应证.     

肝癌肝移植16例体会

目的：总结肝癌肝移植的临床经验，探讨原位肝移植治疗原发性肝癌的疗效。方法：回顾分析2004年7月至2006年4月16例原发性肝癌肝移植的临床资料，均采用同种异体（尸体供肝）原位全肝移植，其中7例符合Milan标准，9例符合UCSF标准。结果：16例手术全部成功，围手术期死亡2例，随访2个月-24个月，死亡2例，1例术后3个月死于胆道铸型综合征、胆道感染，1例术后6个月死于胸腰椎转移、肺转移癌，现存活12例，1例带瘤生存。结论：肝移植是原发性肝癌的有效治疗手段，应严格掌握适应证。     

肝脏移植治疗肝癌的价值——附巨大肝癌肝脏移植一例报道

随着肝移植技术的日臻成熟以及器官保存液(University of Wiscontion，UW)和各种免疫抑制剂的应用，肝移植手术的成功率及术后1年成活率逐渐增高。我们于2002年8月成功为—巨大肝癌患者实施了原位肝移植，目前患者状况良好，报道如下。     

肺移植术后肺癌1例报告并文献复习

背景与目的肺移植是治疗终末期肺部疾病的有效手段,然而对肺移植术后肺癌却缺乏了解。我们通过对1例肺移植术后肺癌患者临床资料的报道,并结合相关文献复习,以提高对肺移植术后肺癌的认识、诊断及治疗水平。方法 2007年5月我院为一例65岁、术前诊断为两肺特发性肺间质纤维化(idiopathic pulmonary fibrosis,IPF)的男性患者在体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)辅助下成功进行了右侧单肺移植,患者术后46d恢复良好出院。术后免疫抑制方案为他克莫司(Tac)+吗替麦考酚酯(骁悉)+类固醇激素。出院后患者定期随访。结果在移植术后13个月随访确诊为非移植侧左肺小细胞肺癌伴多发骨转移。患者给予依托泊苷联合顺铂(EP方案)化疗4次症状有所缓解,患者在诊断肺癌后11个月死亡。结论肺移植术后肺癌严重影响移植患者远期存活,慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)、IPF、吸烟史及免疫抑制剂等为其危险因素,为改善预后,需要早期诊断及早期治疗。     

肝移植治疗晚期原发性肝癌

目的:总结肝脏移植治疗晚期肝癌的初步经验.方法:对2例晚期肝癌接受肝移植患者的临床资料作回顾性分析.结果:2例患者手术均获得成功,术后生活质量提高,1例术后15个月死于全身衰竭,另1例术后17个月死于脑转移.结论:肝脏移植术可以提高晚期肝癌患者的生活质量,并延长患者生存期.经典原位肝脏移植术可以作为晚期肝癌的治疗选择.     

肝移植治疗晚期原发性肝癌

目的：总结肝脏移植治疗晚期肝癌的初步经验。方法：对2例晚期肝癌接受肝移植患者的临床资料作回顾性分析。结果：2例患者手术均获得成功，术后生活质量提高，1例术后15个月死于全身衰竭，另1例术后17个月死于脑转移。结论：肝脏移植术可以提高晚期肝癌患者的生活质量，并延长患者生存期。经典原位肝脏移植术可以作为晚期肝癌的治疗选择。     

Rapid progression from oral leukoplakia to carcinoma in an immunosuppressed liver transplant recipient

Immunosuppression used to avoid graft rejection in solid organ transplantation recipients leads to a variety of side-effects, and an increased rate of infections and de novo malignancies. Oral conditions usually associated with immunosuppressive drugs include fungal and viral infection, and lip lesions, but intra-oral carcinoma has not been reported as having a high incidence. This report deals with a male liver transplant recipient receiving FK506 (5 mg/day) and prednisone (20 mg/day) who was diagnosed with a homogeneous leukoplakia on the floor of the mouth 4 months after transplantation, and 4 months later with a squamous cell carcinoma growth at the site of this lesion. The rapid transformation of the lesion suggests that in patients who display oral premalignant conditions, immunosuppression must be considered as an important risk factor for oral cancer.     

原位肝移植治疗原发性肝癌６８例报告

目的：探讨原位肝移植在原发性肝癌治疗中的价值。方法：对６８例接受肝移植原发性肝癌病例进行回顾性分析,随访６个月以上,对术后患者存活情况进行分析。结果：６８例肝移植手术均获成功,无围手术期死亡,５４例存活至今,最长无瘤存活已达６５个月。小肝癌复发率为２.２％（１／４６）,大肝癌复发率为５４.５％（１２／２２）,其中肝内门脉分支有癌栓者复发率为６６.６％（４／６）,门脉主干有癌栓者为１００％（３/３）;小肝癌患者的存活时间显著长于大肝癌（Ｐ＝０.０００）。此外,肝癌肝移植术后及早停用类固醇激素,并维持抗排斥药物在较低的药物浓度也可能有助于减少肿瘤术后复发。结论：原位肝移植是治疗肝癌特别是小肝癌的有效手段,对于门静脉主干无癌栓的中晚期肝癌也能起到积极治疗作用。     

Immunomodulation with FK506 around the time of intravenous re-administration of an adenoviral vector facilitates gene transfer into primed rat liver

Although adenoviruses are an attractive vehicle for gene transfer into tissues including various tumors, in vivo adenoviral administration elicits a neutralizing antibody response which eliminates or substantially reduces the efficacy of subsequent treatments. Transiently immunosuppressive strategies at the time of initial adenoviral exposure have shown to prevent the formation of neutralizing antibodies and permit the successful adenoviral readministration in animals. Initial treatment in humans may, however, correspond to adenoviral readministration into animals, because the exposure to wild-type adenoviruses is common in humans. In the present study, we infused Adex1CAlacZ adenoviruses carrying the lacZ gene into the tail vein of rats, and examined whether a transient treatment with the immunosuppressant FK506 around the time of i.v. readministration of adenoviruses could induce the re-expression of the lacZ gene in animals primed with adenoviruses. Although i.v. infusion of adenoviruses carrying the lacZ gene resulted in transiently high levels of transgene expression in rat liver, i.v. reinfusion of adenoviruses failed to induce detectable levels of transgene expression. Conversely, when animals were treated transiently with FK506 around the time of adenoviral reinfusion, development of neutralizing antibodies and antigen-specific T cell proliferation in response to adenoviral reinfusion were significantly suppressed, and re-expression of the transgene was achievable.     

Optimal therapeutic concentration of tacrolimus in adult patients undergoing reduced-intensity cord blood transplantation

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.     

Transplantation for liver and biliary cancer

The early survival of patients transplanted for liver and biliary cancer is excellent, but the overall mid- to long-term survival is poor. In an era of severe donor organ shortage, it is not justified to allocate donor liver to patients with a suboptimal outcome. Patients with non-resectable hepatocellular carcinoma in a non-cirrhotic liver should not be assigned to liver transplantation. Although patients with the fibrolamellar variant have a somewhat better outlook, they are still likely to recur, and the young age of many of these patients is likely to overwhelm any rational approach. The results of transplantation for early-stage hepatocellular carcinoma in a cirrhotic liver are similar to those achieved with benign disease. The inclusion of such cases as a group is justified, but attempts should be made to resect tumors whenever possible and to not assign the entire group to transplantation as the first and only option. The value of pre- and postoperative adjuvant therapy for this group is still under debate, but the present waiting period is so long that some form of therapy to slow growth and prevent dissemination of tumor cells is probably required. The results following transplantation for cholangiocarcinoma can only be regarded as dismal, and the diagnosis of cholangiocarcinoma is a contraindication for the procedure. Liver transplantation has a definite place in the treatment of epithelioid hemangioendothelioma and unresectable chemo-responsive hepatoblastoma when confined to the liver, and in a limited number of metastatic neuroendocrine tumors.     

Anti-tumor-promoting action of FK506, a potent immunosuppressive agent

The effect of FK506, a potent immunosuppressive agent, on 7,12-dimethylbenz[a]anthracene-initiatedand 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skinpapilloma formation was examined in CD-1 mice. A topical applicationof FK506 to mouse skin 15 min before each TPA treatment resultedin a dose-related inhibition of tumor formation. FK506 (1 µmol)almost completely inhibited tumor formation. This inhibitoryeffect of FK506 was not due to any damage inflicted on the initiatedcells but due to its antitumor-promoting action. A topical applicationof FK506 also inhibited epidermal ornithine decarboxylase inductionand skin inflammation caused by TPA in a dose-related manner.Significant inhibition by FK506 of TPA-induced endogenous proteinphosphorylation in intact epidermal cells was not detected.These results indicate that FK506 inhibits TPA-induced tumorpromotion at a step distal to the endogenous protein phosphorylationby TPA.     

Modulation of multidrug resistance by immunosuppressive agents: cyclosporin analogues, FK506 and mizoribine.

It has recently been reported that an immunosuppressive agent, cyclosporin A, shows a potent overcoming effect on multidrug resistance (MDR). We studied the presence of such a modulating effect of cyclosporin analogues and other immunosuppressive agents, FK506 and mizoribine, in human multidrug-resistant ovarian cancer cells (TAOV/A0.2). The intensity of the overcoming effect of cyclosporin analogues against adriamycin resistance was found to be in the other of cyclosporin D greater than A greater than C greater than H. It was found that cyclosporin D, which has relatively weak immunosuppressive activity, overcame adriamycin resistance in the multidrug-resistant ovarian cancer cells to a remarkable degree. On the other hand, it was found that FK506, a new potent immunosuppressant, could also distinctly modulate adriamycin-resistance. It was found that FK506 conferred chemosensitization upon adriamycin with reincreasing intracellular adriamycin accumulation in MDR cells which was far less than the parent strain. However, in the case of mizoribine, no modulation of drug resistance existed. Such modulation was not necessarily accompanied by immunosuppressive activity and the two functions were thought to be based on different mechanisms.     

免疫抑制剂FK506对肺癌细胞增殖和迁移的作用研究

背景与目的 FK506(他克莫司,tacrolimus)是一种大环内酯类的新型免疫抑制剂.研究报道FK506对多种肿瘤细胞具有增殖抑制作用.本研究旨在观察FK506对肺癌细胞增殖和迁移的作用,并探讨其可能的机制.方法 体外培养A549和H1299细胞,采用CCK-8法测定FK506对A549和H1299细胞增殖的作用;EDU标记法检测DNA合成;流式细胞术检测细胞的周期分布情况;Transwell和细胞划痕实验检测细胞的体外迁移能力;Western blot技术检测P27、RB1、CDK4、CDK6和MMP9蛋白的表达.结果 FK506可抑制A549和H1299细胞的增殖、诱导细胞周期G0期/G1期阻滞;与对照组比较,FK506处理后A549和H1299细胞迁移能力明显降低,且呈剂量依赖性.此外,与对照组相比,FK506处理组中P27和RB1表达上调,而CDK4、CDK6和MMP9表达显著下降.结论 FK506对人肺癌A549和H1299细胞的增殖和迁移能力有明显的抑制作用,其机制可能与上调p27表达、抑制CDK4、CDK6和MMP-9表达有关.