Computed tomographic features of colorectal carcinoma liver metastases predict posthepatectomy patient survival

PURPOSE: The gross appearance of colorectal carcinoma liver metastases reflects the biologic behavior of the tumor, yielding prognostic information. The aims of this retrospective study were to determine whether preoperative computed tomographic features of colorectal carcinoma liver metastases reflect the gross appearance of resected specimens and whether these computed tomographic hepatic features predict survival after hepatectomy. METHODS: Eighty-five patients underwent curative partial hepatectomy for colorectal carcinoma liver metastases. Preoperative computed tomographic features of the largest hepatic deposit were classified by the contour of advancing margin of the tumor into two types: lobular tumors with indentations with an acute angle and nonlobular tumors without such indentations. The correlation between computed tomographic features and 18 other clinicopathologic factors was examined. RESULTS: The overall five-year survival rate was 34.1 percent. Of 85 hepatic tumors examined, 49 were lobular and 36 were nonlobular. Computed tomographic features correlated significantly with gross appearance (P = 0.007). Univariate analysis revealed that computed tomographic features (P < 0.0001), gross appearance (P = 0.0063), size of the largest hepatic deposit (P = 0.0075), age (P = 0.0140), and satellite lesions (P = 0.0443) were significant prognosticators. The five-year survival rates in patients with lobular and nonlobular tumors were 10.4 and 66.1 percent, respectively. By multivariate analysis, computed tomographic features (P < 0.0001) and size of the largest hepatic deposit (P = 0.0419) were independently significant. CONCLUSIONS: Computed tomographic features of colorectal carcinoma liver metastases correlate with their gross appearance. The computed tomographic characterization of liver metastases is the most important independent prognostic factor in patients undergoing curative hepatectomy.     

HBV转基因小鼠暴露ATB-1后肝脏ATB-1-DNA加成物水平的测定

目的探讨ＨＢＶ与ＡＴＢ１协同致肝癌的机理．方法用ＲＩＡ法测定ＨＢＶ转基因小鼠与正常小鼠暴露ＡＴＢ１后０，０５，１，２，４，８，２４ｈ７个不同时相肝脏ＡＴＢ１ＤＮＡ加成物的含量变化．结果暴露ＡＴＢ１后，ＨＢＶ转基因小鼠肝脏ＡＴＢ１ＤＮＡ加成物含量在各时相均高于正常小鼠，尤以１ｈ高峰时相值（５５９２ｐｍｏｌ／ｍｇ±４１５ｐｍｏｌ／ｍｇ比４１３６ｐｍｏｌ／ｍｇ±２８２ｐｍｏｌ／ｍｇＤＮＡ，Ｐ＜００１）及２４ｈ时相值（２４８７±２０３比９８９±８５，Ｐ＜００１）最显著．２４ｈ后，转基因小鼠肝脏ＡＴＢ１ＤＮＡ加成物仍维持高水平，但正常小鼠已基本恢复至暴露前水平．结论ＨＢＶ转基因小鼠暴露ＡＴＢ１后肝脏ＡＴＢ１ＤＮＡ加成物含量增加可能为ＨＢＶ与ＡＴＢ１协同致肝癌的直接原因．     

Hepatic encephalopathy in patients with liver cirrhosis：Is there a role of malnutrition？

Hepatic encephalopathy（HE） is a common complica-tion in patients with liver cirrhosis but its pathogenesis remains incompletely understood.Malnutrition is commonly encountered in patients with liver cirrhosis and it has been reported to affect the quality of life of this group of patients.Experimental studies suggest that low energy intake and poor nutritional status may facilitate the development of HE but there are scarce data on the potential role of malnutrition in HE in patients with liver cirrhosis.Two recently published studies have evaluated the potential role of malnutrition in the development of HE in cirrhotic patients with conflicting results.In this letter to the editor we briefly present the results of the two studies as well as potential reasons for the conflicting results reported.     

粒细胞集落刺激因子对四氯化碳所致小鼠慢性肝损伤的治疗作用

目的 观察重组人粒细胞集落刺激因子(rhG-CSF)对四氯化碳(CCl4)所致小鼠慢性肝损伤的治疗作用.方法 清洁级雄性BALB/C小鼠分为治疗组与对照组.每周2次CCl4腹腔注射制备慢性肝损伤模型.造模成功后治疗组给予rhG-CSF(200 μg·kg-1·d-1)皮下注射7 d,对照组给予同等剂量0.9%氯化钠溶液.测定小鼠体质量、肝重和脾重.采用临床常规方法检测肝功能、肝纤维化指标.对肝纤维化程度进行评分.流式细胞仪计数分析肝组织中CD34+细胞,免疫组化法测定Thy-1+表达.结果 治疗组小鼠第8和15天时脾重与肝重比值(15.94%±1.20%和10.52%±0.66%)与对照组(7.14%±1.68%和8.31%±1.71%)比较差异有统计学意义(P值均＜0.05),两组小鼠体质量和肝重差异无统计学意义(P＞0.05).第15天时治疗组小鼠白蛋白水平快速上升.第30天时治疗组丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、透明质酸(HA)、层粘连蛋白(LN)水平均低于对照组.第30天时两组肝纤维化程度计分差异有统计学意义(治疗组5.49±2.16,对照组8.74±1.86,P＜0.05).治疗组小鼠肝脏组织中CD34+细胞和Thy-1+阳性细胞数在第8天(9.54±2.24和5.10±1.25)和第15天(8.18±1.93和7.53±1.39)时高于对照组(第8天时5.40±0.99和3.25±0.75;第15天时4.46±0.77和3.35±0.86,P值均＜0.05).结论 rhG-CSF能促进慢性肝损伤的恢复,将为肝纤维化提供一个新的治疗方法.     

The Effect of Processing on Liver Biopsy Core Size

OBJECTIVES: Liver biopsy is a valuable clinical tool, but for the interpretation to be meaningful a certain core size should be obtained. This study examines the changes the liver biopsy core undergoes during processing steps. METHODS: A total of 61 consecutive percutaneous liver biopsies were obtained between November 2004 and April 2005. The needle type utilized was the 16-gauge automatic tru-cut. A measurement was made while each liver biopsy core specimen resided in the cartridge, then a measurement was made with the core placed on the tray, and a final measurement was made after the pathologist received the formalin-fixed specimen. RESULTS: The mean size of the biopsy core in the cartridge measured 15 +/- 2 mm, compared to a mean size on the tray of 19.6 +/- 3.5 mm, and a mean size after fixation of 18.3 mm. All mean sizes were statistically different from one another. The compressive effect of the cartridge was 23%. The shrinkage effect of formalin fixation was 7%. CONCLUSIONS: The liver biopsy core size changes significantly through the processing steps. It is imperative that the operator is aware of these changes so that appropriate decisions are made. As an example, if the operator underestimates the core size when measured in the cartridge, a second pass may be completed when in fact adequate tissue had been obtained on the first pass.     

三种大鼠脂肪肝模型的比较

目的比较胃造瘘法、酒精灌胃法制作酒精性肝病及高脂营养饮食复制非酒精性肝病的三种动物模型制作方法和优缺点,为酒精性肝病的研究奠定更有效的模型基础.方法分别从胃造瘘管内注入56%白酒,至每次18 ml/kg·d,和经胃灌入同样白酒16～18 ml/kg·d,早、晚各1次,制作胃造瘘和酒精灌胃大鼠模型;又给刚断乳SD雄性大鼠喂养自制营养高脂饲料,复制肥胖性脂肪肝模型.实验开始后4、8、12、24周,在各实验组中随机取8只大鼠,心包腔穿刺取血,测肝功及血糖、血脂:并取小块肝组织分作光镜和电镜观察.结果酒精灌胃组大鼠总体死亡率较高,达37.9%.胃造瘘组仅16.0%,两组相比差异非常显著,P＜0.01.营养性肥胖模型组大鼠体重增长迅速,至12周时已达434.6±30.4g,24周时达502.16±16.4g,分别明显高于对照组的356.9±31.4g和433.1±36.9g,T=4.3l,P＜0.01.也明显高于另两组大鼠体重332.5±24.8g,412.5±34.4g和345.6±25.6g,430.6±26.9g,P＜0.01.各模型组肝指数与相应之对照组比较,8周时始有显著差异,P＜0.05;24周时差异更加显著,P＜0.01.模型组血清肝功转氨酶较对照组显著升高,P＜0.01;24周各模型组白蛋白明显下降,分别为28.04±2.42g/L,29.15±3.21g/L;28.56±193 g/L,与对照组相比有显著差异,P均＜0.05.肥胖模型组TCH、TG显著高于对照组,P＜0.01和P＜0.05,血糖GLU与对照组相比无显著差异.各模型组8W时即可见脂肪肝的各种病理改变,12W时肝纤维化已明显形成.结论胃造瘘法克服了酒精灌胃模型的缺点,是适合我国国情的简便易行、经济可靠、死亡率低的酒精性肝病动物模型,值得推广应用.     

细胞色素P450 2C19基因多态性与原发性肝细胞癌的相关性研究

细胞色素P450（CYP）2C19代谢美芬妥英的酶活性在人群中呈快代谢型和慢代谢型二态分布。突变型等位基因是CYP2C19基因多态性的分子生物学基础。目的：对原发性肝细胞癌（HCC）患者的CYP2C19等位基因进行基因分型．探讨CYP2C19基因多态性与原发性HCC的关系。方法：纳入48例原发性HCC患者和88名健康对照者。设计相应引物，以聚合酶链反应．限制性片段长度多态性（PCR-RFLP）方法检测CYP2C19ml和CYP2C19m2突变型等位基因．对两组基因多态性进行分析比较。结果：HCC组CYP2C19慢代谢型（ml／m1和ml／m2）发生率为25．0％（12例）．与健康对照组的11．4％（10例）相比差异有统计学意义（P〈0．05，OR=3116，95％CI：1140—7113）。结论：CYP2C19慢代谢型与原发性HCC之间存在相关性，可能增加人群对HCC的易感性。     

交感神经递质及其受体在小鼠血吸虫肝纤维化中的作用

目的 研究交感神经递质及其受体在正常小鼠及血吸虫病肝纤维化小鼠体内的变化情况.方法 应用腹部敷贴尾蚴法制备血吸虫病小鼠模型.30只昆明小鼠随机分为正常对照组和肝纤维化模型组.采用HE和Van Gieson染色,光镜观察肝组织病理学改变及纤维化程度,免疫荧光组织化学染色结合激光共聚焦扫描检测肝组织中α1A、β2肾上腺素能受体表达情况,同时用高效液相色谱-电化学法检测血浆中去甲肾上腺素和多巴胺的水平. 结果 正常组α1A、β2肾上腺素能受体散在表达于肝细胞胞质和肝窦内,模型组在门静脉和虫卵结节周围肝细胞胞质中阳性表达明显增加(α1A受体的平均灰度值分别为18.28±7.56、30.53±8.88,β2受体的平均灰度值分别为28.67±6.42、42.29±4.56,t值分别为-2.888和-6.648,P值均＜0.05);血吸虫肝纤维化小鼠和正常小鼠去甲肾上腺素含量分别为(7.83±4.36)、(2.72±0.94)ng/ml,多巴胺的含量分别为(6.97±4.33)、(0.74±0.34)ng/ml,t值分别为-3.372和-4.428,P值均＜0.05.结论 交感神经递质及其受体表达的上调可能是血吸虫肝纤维化发展的作用机制之一.     

HLA-DRB1和肿瘤坏死因子α基因多态性与肝硬化的遗传易感性

目的探讨HLA-DRB1和肿瘤坏死因子(TNF)α基因多态性与肝硬化遗传易感性之间的关系.方法应用聚合酶链反应-序列特异性引物法、限制性片段长度多态性等技术检测106例乙型肝炎后肝硬化患者和108例健康对照者的HLA-DRB1和TNFα基因多态性.结果肝硬化组HLA-DRB1*120X等位基因频率比对照组显著升高(35.9%比11.1%,P＜0.001),TNFα中TNF2/1基因型频率比对照组明显升高(19.8%比10.2%, P＜0.05),DRB1*150X等位基因频率明显低于对照组 (13.2%比30.6% ,P＜0.05),分层分析表明,DRB1*120X等位基因与肝硬化的关联大于TNF2等位基因.结论 HLA-DRB1*120X和TNF2等位基因与乙型肝炎后肝硬化的遗传易感性相关,携带这2个等位基因的个体发生肝硬化的危险性增加.HLA-DRB1*120X等位基因可能是肝硬化的易感基因,HLA-DRB1*150X等位基因为抗性基因.     

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology

Background/Aims: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure.Methods: The 5′-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12).Results: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25%, and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure.Conclusions: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.