肝移植术后丙型肝炎病毒感染

目的：探讨肝移植术后丙型肝炎病毒感染的危险因素及处理对策。方法：回顾性分析2001年4月～2005年2月间，复旦大学附属中山医院15例肝移植术后丙型肝炎病毒感染的临床资料，了解相关危险因素、诊断、治疗及预后情况。结果：15例中9例肝移植术后HCV复发，血清中检测到HCVRNA，和(或)出现病理肝活检组织学改变。3例死亡皆因HCV复发不能控制所致。干扰素-α联合利巴韦林治疗4例，HCVRNA血清滴度在治疗后1周皆明显下降。结论：HCV复发是目前肝移植术后一个普遍而又处理棘手的问题。控制并减少HCV复发的危险因素，早期诊断并进行有效的预防和治疗，是提高丙肝肝移植效果的重要途径。     

原发性肝癌伴门静脉癌栓手术病人的预后因素

目的 :研究影响原发性肝癌伴门静脉癌栓手术病人预后的临床病理因素。方法 :随访 83例手术切除的原发性肝癌伴门静脉癌栓病人 ,其中 6 4例术后行门静脉和 (或 )肝动脉化疗栓塞。单因素分析各因素对生存率的影响。多因素分析用Cox风险比例模型。结果 :原发性肝癌伴门静脉癌栓单纯手术病人的中位生存时间 10 .3个月 ,若术后行各种化疗栓塞 ,病人的中位生存时间 13.4个月 ,其 1、2、3年生存率分别为 37.6 %、30 .7%、14 .0 % ,明显高于单纯手术组 (P <0 .0 5 )。单因素分析提示肿瘤大小、Edmondson分级、术后化疗栓塞次数是影响病人预后的主要因素。多因素分析提示Edmondson分级、术后化疗栓塞次数影响手术病人的预后。结论 :Edmondson分级、术后化疗栓塞次数是影响原发性肝癌伴门静脉癌栓手术病人预后的主要因素。术后门静脉和 (或 )肝动脉化疗栓塞可改善病人的预后     

IL-12与粒细胞-巨噬细胞集落刺激因子基因联合治疗小鼠肝癌的研究

目的 研究L-12与粒细胞-巨噬细胞集落刺激因子(granalocyte-macrophage-colong scimulatingfactor,GM-CSF)联合基因治疗对小鼠皮下肝癌的治疗作用。方法 将皮下接种1×106BNL肝癌细胞的小鼠分四组于肿瘤接种3、6d后分别经尾静脉高压注射总量为25μg的细胞因子编码质粒:(1)pXX-GM-CSF、pXX-IL-12各 12.5μg;以pXX-IL-12 25μg;(3)pXX-GM-CSF 25μg;(4)pXX-Neo 25μg,每组6只小鼠。观察小鼠皮下肿瘤生长情况及所诱导的细胞免疫反应。同时研究了经尾静脉高压注射后小鼠血清IL-12、GM-CSF和IFN-γ浓度变化。结累IL-12与GM-CSF联台基因治疗可以诱导更强的抗肝癌免疫和细胞免疫反应。GM-CSF可以增强IL-12分泌并减少其诱导的IFN-γ分泌。结论IL-12和GM-CSF联台基因治疗可以产生较强的抗瘤作用并能减少IL-12的副作用。     

STAT3在肝癌中发挥致癌和抑癌双重作用

研究发现,在不同类型肿瘤中均存在STAT信号通路的过度激活.在STAT信号通路中,通过细胞外配体包括细胞因子、激素和生长因子,特异性结合受体,进而激活Janus酪氨酸激活酶(包括Jak1,Jak2,Jak3和Tyk2).酪氨酸激活酶可对每个Stat蛋白酪氨酸的残端磷酸化.同样,非受体激活型酪氨酸激活酶(例如c-ABL和c-SRC),可不通过受配体信号的激活,而直接对Stat蛋白磷酸化.Stat蛋白磷酸化后会形成同类二聚体或者异类二聚体,进入细胞核,激活相关靶基因,从而调控细胞增殖、存活、血管形成、侵袭和转移.Stat蛋白进入核内同时激活了三大抑制蛋白家族,包括Stats激活抑制蛋白(PIAS)、SH2型磷酸酶以及细胞因子信号抑制物(SOCS).三条抑制途径随着Stat途径的激活而激活,从而可有效抑制Stat对靶细胞的效应,表现为一种负反馈调控.     

53例肝癌切除术后生存20年以上远期随访分析

Objective To clarify the clinicopathological features of patients surviving≥20 years after resection for hepatoceUular carcinoma(HCC).Methods Between 1961 and 1987, a total of 396 patients underwent hepatic resection for HCC.Of the 396 patients, 53(13.4 %) survived ≥20 years and 343(86.6%) <20 years.A comparative study between the two groups was made.Results By March of 2007, 67.6%(36/53) of the patients were still alive and disease-free while 5.7% (3/53) of them died of tumor recurrence or metastasis, 11.3 % (6/537 died of liver failure, 5.70% (3/537 died of other disease, and 9.4% (5/53) were lost during follow-up.Two patients with intraperitoneal rup-tured HCC survived fro 26.6 years and 38.75 years, respectively.Five young patients got married af-ter resection and have had babies.The longest surviving time was 43 years and 2 months.Reresection for recurrence was done in 9 patients and the mean survival was 26 years and 11 months.Reresection for solitary pulmonary metastasis was performed in 3 patients and the mean survival was 29 years and 2 months.Downstaging followed by resection was performed in 4 patients, mean survival being 22 years and 10 months.In comparison with patients surviving <20 years, those surviving ≥20 years were significantly younger(P<0.05) and had a higher incidence of asymptomatic tumors (P<0.01), lower γ-glutanyl transpeptidase levels (P<0.01), lower incidence of liver cirrhosis (P<0.01) ; high-er percentage of smaller tumors (P<0.01), single nodule tumors (P<0.01) and well encapsulated tumors (P<0.01), lower incidence of tumor emboli in portal vein (P<0.01), better differentiation of tumor cells (P<0.05) and higher curative resection rate (P<0.01).Conclusions Early and cura-tive resection are important for improving long-term survival.Long-term follow-up after resection of HCC is very important, and should continue for the remainder of the patient's life.Reresection for re-currence and metastasis is an important approach to improve prognosis.     

肝癌患者肝移植术后肿瘤复发相关的血清蛋白质标记物筛选

Objective To appraise and compare protein expression profiles in sera of patients without or with recurrence following liver transplantation for hepatocellular carcinoma (HCC) using SELDI-TOF-MS technique,and establish the diagnostic and predictive model. Methods A total of 76 sera (41 from disease free survival patients and 35 from recurrence individuals) were collected pretransplantation and differentially expressed proteins were identified by SELDI-TOF-MS. The intensity values for each peak were analyzed by Biomarker Wizard Software to screen serum proteome biomarkers related to the recurrence post-transplantation. By using Biomarker Patterns Software, the classification trees were generate. from randomly selected samples (30 fingerprints obtained from each group). The sensitivity and specificity of best decision tree were then chosen for blind test with 16 samples (5 from recurrence individuals and 11 from recurrence-free survival patients). Results There were significant differences only in tumor size and the presence of vascular invasion between recurrence group and recurrence-free survival group (P＜0.05). According to serum protein fingerprints, a total of 368 protein peaks were identified at the mass-to-charge ratio (M/Z) value ranging from 2000 to 300 00. There were 22 significant differential proteins between two groups. Among them, 9 proteins were up-regulated and 13 proteins were down-regulated -espectively in recurrence group. The intensity values of differential proteins were input into BPS for classification tree analysis and the best performing tree could distinguish two groups successfully. As a result of blind assessment for this model,a sensitivity of 80.0 % (4/5) and specificity of 72.7 % (8/11) were obtained. Conclusion Some of differential proteins screened by SELDI-TOF-MS technique in the serum may be correlated with the prognoses of liver transplantation patients with HCC. The decision tree may be useful for the clinical application of formulating the indication for liver transplantation, detecting extrahepatic micrometastasis and setting up the diagnostic and treatment strategies.     

腺病毒载体研究新进展

近年来,病毒载体尤其是腺病毒载体的研究成为基因治疗研究中的一个热点。本文综述了腺病毒载体的构建和应用方面的最新进展,表明腺病毒载体是基因转移的重要手段,具有众多的优点,在基因治疗领域具有广阔的应用前景。     

围手术期肝功能对肝癌根治术后病人预后的影响

目的　阐明围手术期肝功能对肝癌根治术后病人预后的影响。方法　对 96例病人围手术期肝功能和其他临床病理特征进行生存率的比较 (单因素分析 ) ,并通过Cox多因素分析得到有独立意义的肝功能预后指标。结果　单因素分析示在肝功能指标中 :围手术期白 /球蛋白比 (A/G)、碱性磷酸酶 (AKP)、术前白蛋白、γ 谷氨酰转肽酶 (GGT)、术后一周胆汁酸浓度 (SBA)、丙氨酸转氨酶(ALT)与生存率相关 (P <0 0 5 )。Cox多因素分析示 :术后一周ALT是与生存相关的独立预后因素。另外单因素分析示术前A/G、GGT、AKP、术后一周SBA与无瘤生存率相关。多因素分析示术后一周胆汁酸浓度是与无瘤生存相关的独立预后因素。结论　围手术期肝功能对估计肝癌病人预后有一定作用 ,加强保肝治疗是提高生存率的重要方法之一     

肝癌根治术后区域化疗预防复发的价值

目的评价肝脏区域化疗预防肝癌根治术后复发的作用。方法１９９５年１月至１９９７年１２月行肝癌根治性切除１０５例。全部病例均在术后４～６周经肝动脉或联合门静脉行术后肝脏区域化疗,此后每隔２～４个月重复一次。结果随访４～４０（x=２２．７±９．７）个月。１０５例中２例分别于术后１２、１３个月时死于重症肝炎,但无肝癌复发。１０３例存活者１３例复发,其中余肝复发１１例,肺和腹腔转移各１例。术后１、２、３年的累积复发率分别为１％、１５％和１８％。复发距手术时间为１０—２２（Ｘ＝１５．３±２．９）个月。结论术后肝脏区域化疗可明显降低肝癌根治术后复发高峰期的复发率。