脾切除和门奇断流术对肝炎后肝硬化肝癌发生的影响
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摘要
原发性肝癌(hepatocellular carcinoma,HCC)是最常见的恶性肿瘤之一,占肝脏原发性肿瘤的近90%,我国每年新增HCC病例约35万人,约32万人死于此病,其发病率和死亡率之高,成为我国仅次于胃癌和食道癌的常见恶性肿瘤。随着对HCC病因学研究的深入,人们发现HCC的发生是一个多阶段、多因素累积的作用,其中肝炎病毒(乙肝病毒HBV,丙肝病毒HCV)是目前公认的HCC发生的主要病因之一,研究表明,肝炎后肝硬化是HCC发生的主要危险因素之一。肝炎后肝硬化主要的临床表现有肝功能减退和门静脉高压症,目前在门静脉高压症多种外科治疗中以门奇断流术为主,对于各种治疗的远期临床疗效及与HCC的关系已有大量的报道。脾大、脾功能亢进作为肝硬化门脉高压症的主要并发症,在治疗过程中是否切除脾脏,一直以来都存在着争议。目前对脾脏与HCC关系的研究大多集中于脾脏在HCC的进展和治疗过程中的作用,而对脾脏在肝炎后肝硬化进展为肝癌过程中的作用尚无报道。本课题旨在通过探讨脾切除和门奇断流术对HCC发生的影响,为肝炎后肝硬化门静脉高压的治疗和肝癌发生的研究提供理论依据。
     本课题通过设计病例对照研究,确定入组条件,根据诊断标准和排除标准,2005年01月~2007年06月在我院确诊为病毒性肝炎后肝硬化伴门脉高压症患者共625例,收集病例的一般资料、临床及实验室检查数据、影像学检查结果,以及在治疗过程中的脾切除和门奇断流手术史,将病例分为两组,未合并肝癌病例(组1)464例,合并肝癌病例(组2)161例,使用SAS9.0统计软件,对多个研究因素进行单因素分析及多因素logistic回归分析。
     经统计学分析,描述性统计结果显示,两组的年龄差异有统计学意义(P<0.05),而PLT、WBC在两组间差异无统计学意义(P>0.05);两组间构成的检验及单因素分析得出,性别、腹水及肝性脑病情况、Child-Pugh分级、TBIL异常升高在两组间构成差异无统计学意义(P>0.05)。将年龄作为校正因素,单因素分析有意义的研究因素纳入多因素logistic回归方程得知,ALP异常升高增加了肝癌发生的危险性,是ALP正常患者的1.838倍(OR:1.838,95%CI: 1.197~2.824),GGT异常升高使肝癌发生的危险性较GGT正常患者增加7.95倍(OR:7.950,95%CI: 5.0981~2.397),而行脾切除和门奇断流术明显降低了肝癌发生的危险性,仅为无手术患者肝癌发生危险性的43.6%(OR:0.436,95%CI: 0.219~0.871)。
     目前,对肝炎后肝硬化门静脉高压症的病理脾脏在肝癌发生中影响的研究尚未见报道,本研究发现,脾切除和门奇断流术可显著降低肝炎后肝硬化伴门脉高压,脾大,脾功能亢进患者肝癌发生的危险性, ALP和GGT的异常升高则提示其肝癌发生的危险性增加。病理脾脏可能在肝炎后肝硬化门静脉高压患者HCC发生过程中起到一定促进作用,切除病理脾脏可能降低HCC发生的危险性,对这一结论的进一步研究,可为肝炎后肝硬化门静脉高压的治疗提供理论依据。
Hepatocellular carcinoma(HCC) is one of the most common malignant tumor, accounting for primary liver tumor for nearly 90 percent, annual new cases of HCC about 35 million people, about 320,000 people died of the disease , The morbidity and mortality rates as high as second only to stomach cancer and esophagus cancer in common in China. As the etiology of HCC in-depth study, people found that the incidence of HCC is a multi-phase, multi-factor cumulative effects, hepatitis virus (HBV, HCV)were recognized as one of the main cause, study showed that the posthepatitic cirrhosis was the major risk factor. The main clinical manifestations of posthepatitic cirrhosis were hypohepatia and portal hypertension, porta-azygous disconention is a main procedure in a variety of surgical treatment of portal hypertension, for the treatment of various clinical efficacy and long-term relationship with the HCC has been a lot reports.
     Hypersplenotrophy, hypersplenism as the main complications in portal hypertension if the splenectomy necessary in the course of treatment, there have always been controversial. At present the relations between the HCC and spleen are mostly concentrated in the spleen on the progress and treatment of HCC's role in the process, but had not been reported the role of spleen in hepatocarcinogenesis . The topic was to investigate the impact of splenectomy wtth porta-azygous disconnection on hepatocarcinogenesis in the patients of posthepatitiscirrhosis, provide a theoretical basis for the treatment of posthepatitic cirrhosis with portal hypertension and the study of hepatocarcinogenesis.
     This topic through case-control study designed to determine the group conditions, according to diagnostic criteria and exclusion criteria,from January 2005 to June 2007 six handred twenty five posthepatitis cirrhosis with portal hypertension and hypersplenism patients in our hospital were include in this study. Among them 464 cases without hepatocellular carcinoma(HCC) (group1) ,161 cases with HCC(group2). General information,clinical and laboratory examination datas, imaging examination results and history of splenectomy with porta-azygous disconention were collected. Univariate and multivariate logistic regression analysis of the impact of splenectomy with porta-azygous disconnecton on hepatocarcinogenesis were performed by SAS9.0
     Statistical results showed that between group 1 and 2 there was statistically significant difference in age(P<0.05),but no statistically significant difference in gender, ascites, hepatic encephalopathy, live function(child-pugh)class,total bilirubin and platelet count(P>0.05). Single-variable and multivariate analysis revealed that the patients with abnomal of alkaline phosphatase(ALP)increased 1.838 times risk of hepatocarcinogenesis(odds ratio ,OR:1.838; confidence interval of 95%: 1.197~2.824),abnomal ofγ-glutamyltransferase(GGT) increased 7.950 times risk of hepatocarcinogenesis (OR:7.950,95%CI: 5.098~2.397).Compareing patients with and without history of splenectomy with porta-azygous disconection ,this procedure significant reduced the risk of hepatocarcinogenesis(OR:0.436,95%CI: 0.219~0.871)
     At present, the impact of patho-spleen on hepatocarcinogenesis of posthepatitic cirrhosis with portal hypertension has not been reported, the study found, splenectomy with porta-azygous disconention procedure could significantly reduce the risk of hepatocarcinogenesis in patients of posthepatitic cirrhosis with portal hypertension, hypersplenotrophy and hypersplenism, The abnomal of ALP and GGT increasee risk of hepatic carcinoma in these patients .Patho-spleen may have a promotion role of hepatocarcinogenesis in patients of posthepatitic cirrhosis with portal hypertension ,splenectomy may reduce the risk of hepatocarcinogenesis, to the conclusion that further studies for splenectomy with porta-azygous disconention may provide a theoretical basis in the treatment of posthepatitic cirrhosis with portal hypertension
引文
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