原发性肝癌线粒体DNA微卫星不稳定性研究

用PCR厅法检测了原发性肝癌组织线粒体DNA微卫星不稳(mtMSI)和核DNA微卫星不稳(nMSI),阐明其在原发性肝癌发生中的作用,揭示原发性肝癌的发病机制。 1.资料与方法:收集本院手术切除的肝癌组织52例,每例抽血5 ml,分离淋巴细胞。肝癌和淋巴细胞基因组DNA的提取采取酚/氯仿异戊醇提取法。参照文献合成7对引物,包括2个控制区(D-loop)区和5个编码区的mtDNA微卫星序列。用     

乙型肝炎DNA聚合酶的临床意义

本文采用特异性免疫沉淀法对163例肝炎患者进行了DNA聚合酶(DNA-P)测定。结果表明:以慢活肝、携带者和慢迁肝三者的DNA-P阳性率最高。肝癌的DNA-P检出率位居第四,但平均酶活力最高,提示我国原发性肝癌HBV复制还是显著的。肝硬化的DNA-P检出率和酶活力最低,这可能是大量纤维组织增生妨碍了HBV的肝内增殖。     

肝硬化并发原发性肝癌的流行病学特征、危险因素及相关预防干预对策研究

目的:探讨肝硬化并发原发性肝癌的流行病学特征、危险因素及相关预防干预对策。方法 :将2015年1月到2018年12月收治的175例肝硬化患者依据有无并发原发性肝癌分成研究组77例、对照组98例。统计两组患者临床资料,经多因素Logistic回归分析法分析肝硬化并发原发性肝癌危险因素。结果:肝硬化并发原发性肝癌的男性、女性患病率分别是89.61%(69/77)、10.39%(8/77);≤20岁、21～40岁、41～60岁、60岁患者的患病率分别为3.9%(3/77)、11.69%(9/77)、58.44%(45/77)、25.97%(20/77);单因素分析结果显示:肝硬化并发原发性肝癌和患者吸烟史、合并糖尿病、饮酒史、未接受抗病毒治疗、原发性肝癌遗传史、HBV DNA阳性、HBV DNA10~4copies/ml存在相关性,差异有统计学意义(P0.05);多因素Logistic回归分析显示:长期吸烟、合并糖尿病、长期饮酒、未接受抗病毒治疗、原发性肝癌遗传史、HBV DNA阳性、HBV DNA10~4copies/ml为肝硬化并发原发性肝癌独立危险因素,差异有统计学意义(P0.05)。结论:肝硬化并发原发性肝癌多见于中年男性,而其发生和患者长期吸烟、合并糖尿病、长期饮酒、未接受抗病毒治疗、原发性肝癌遗传史、HBV DNA阳性、HBV DNA10~4copies/ml有关,故针对上述高危人群,需告知患者戒烟、戒酒,养成良好生活习惯,积极控制血糖,强化日常监测和健康宣教,降低危险因素暴露,以减少肝硬化并发原发性肝癌的危险性。     

网络药理学方法研究茵陈蒿汤对原发性肝癌的作用机制

目的:基于网络药理学虚拟预测的方法,探讨茵陈蒿汤对于原发性肝癌的作用机制。方法:首先,利用TCMSP数据库、DrugBank数据库对茵陈蒿汤所含化学成分进行筛选并预测其作用靶点,通过GeneCards数据库、CTD数据库获得原发性肝癌的相关靶点;然后,利用DrawVenDiagram平台制作韦恩图,获得两者的交集靶点蛋白,通过Cytoscape3.6构建出蛋白互作图;最后,通过DAVID分析工具采集到的靶点蛋白从生物过程(BP)、分子功能(MF)和细胞组分(CC)三方面进行基因本体功能富集分析和KEGG通路分析。结果:从TCMSP、DrugBank数据库筛选出茵陈蒿汤的41种化学成分,其中预测到186个靶点,通过CTD、GeneCards数据库预测200个与原发性肝癌相关的靶点,韦恩图显示186个潜在靶标;结果显示茵陈蒿汤大概通过RNA聚合酶Ⅱ启动子转录的正调控、转录DNA模板、RNA聚合酶Ⅱ启动子转录的负调控、转录的正调控、成纤维细胞增殖的正调控、三叶苷对脂多糖信号通路、蛋白质磷酸化的正调控等生物过程,并涉及转录因子活性、序列特异性DNA结合蛋白、DNA结合、染色质结合、细胞因子活性等分子功能发挥治疗原发性肝癌的作用。结论:其作用机制可能与PI3K-Akt、MAPK信号通路、HTLV-I信号通路、Hepatitis B信号通路、Tuberculosis信号等有关。     

血清乙型肝炎病毒DNA阳性与原发性肝癌危险性关系的前瞻性队列研究

目的 探讨血清HBV DNA阳性与原发性肝癌的关系.方法 以分层抽样方法 对广西隆安县12个乡镇30～55岁农村居民抽样,采静脉血,酶联免疫吸附试验检测ItBsAg,套式聚合酶链反应检测HBV DNA.根据tiBsAg和DNA检测结果,将研究对象分为HBsAg(+)/HBV DNA (+)组(A组)和HBsAg(+)/HBV DNA(-)组(B组);根据1:1匹配原则,从本村电HBsAg(-)者中为前两组观察对象挑选对照,组成HBsAg阴性对照组(C组),对这3组人群进行4年的前瞻性跟踪随访.卡方检验对各组及各因素的发病率进行统计分析,然后用Cox比例风险模型分析与PLC有关的危险因素,用后退法对数值进行迭代分析. 结果30～55岁人群HBsAg阳性率为14.52%(3975/27 379),HBsAg阳性者HBV DNA阳性率为40.35%(1604/3975).A、B两组总的肝癌发病率为672.45/10万人年,明显高于C组的17.19/10万人年(P<0.01),相对危险度为39.123,95%可信区间为9.018～159.146.A组肝癌发病率为984.03/10万人年,显明高于C组的324.38/10万人年(P<0.01),相对危险度为3.034,95%可信区间为1.795～5.125.对A、B两组进行肝癌危险因素的多因素Cox模型分析,结果表明性别、年龄、血清HBV DNA阳性、肝癌家族史和以玉米为主食均为肝痛的危险因素. 结论 血清HBV DNA阳性可增加HBsAg阳性者的肝癌危险性.     

原发性肝癌

原发性肝癌染色体17P微卫星不稳定性及突变型P53蛋白的表达，原发性肝癌细胞核和线粒体DNA微卫星不稳定性研究，转化生长因子-β1对原发性肝癌诊断与鉴别的临床价值，肝脾动脉联合栓塞治疗原发性肝癌合并脾功能亢进的临床观察，沙培林在原发性肝癌介入治疗(TACE)中的初步应用研究，中晚期原发性肝癌二期切除26例临床分析。     

肝硬化,肝癌患者与乙肝病毒感染的关系研究

对585例肝硬化及372例肝癌用固相放免法检测HBsAg、抗HBs和抗HBc;用DNA聚合酶链(PCR法)反应测定HBsAg阴性患者血清中HBV DNA;对HBsAg阳性者测定pre-S_2。结果表明:HBV与肝硬化、肝癌有非常密切的关系,二者HBV感染率分别为93.16%和97.3%;HBsAg阴性者中有24.2%HBV DNA阳性;HBsAg阳性的肝硬化、肝癌患者pre-S_2抗原明显高于其它肝病患者,有显著性差异(p<0.02),它们的检出率分别为84.0%和98.4%。     

乙型肝炎病毒相关原发性肝癌的危险因素分析

目的探讨乙型肝炎病毒(HBV)相关原发性肝癌的危险因素。方法 205例HBV感染患者分为HBV相关肝癌组和HBV相关肝病组,两组间年龄、性别、饮酒史等因素比较。结果 1.单因素分析示两组在不良饮食习惯、乙肝病毒载量(HBV DNA)阳性、e抗原(HBeAg)阳性等差异显著(P0.05)。2.logistic回归分析示年龄(≥40岁)、HBV DNA阳性等与HBV相关肝癌相关。结论 HBV DNA阳性、年龄(≥40岁)等可能是HBV相关原发性肝癌的危险因素。     

应用噬菌体展示技术筛选原发性肝癌血清结合蛋白

目的:通过筛选原发性肝癌血清蛋白结合蛋白,探究肝癌的分子发病机制.方法:应用噬菌体展示技术,以肝癌患者的血清作为固相筛选分子,对T7 Select噬菌体人肝细胞cDNA文库进行5轮"吸附-洗脱-扩增"的筛选过程,经噬斑的聚合酶链式反应(PCR)扩增后,对阳性PCR产物直接进行序列测定和同源性分析.结果:噬菌体经富集后,随机挑取48个噬斑进行PCR扩增,得到5种大小不同的PCR片断,序列测定后经序列同源性分析,结果发现与肝癌患者血清蛋白结合的蛋白有以下5种:人核仁螺旋体磷酸化蛋白NOLC1,人高度迁移基核小体结合域1(HMGN1),人依赖ATP的DNA连接酶1(LIG1),人小EDRK-丰富因子2(SERF2)和A-kinase anchor protein 9 isoform.结论:用噬菌体人肝cDNA文库筛选得到了肝癌血清蛋白结合蛋白,为进一步阐明肝癌的发生及发病机制奠定了基础.     

荧光定量PCR检测血清和外周血单核细胞中HBV DNA含量及其意义

通过荧光定量聚合酶链反应(PCR)检测慢性乙型肝炎及肝癌患者血清和外周血单核细胞(PBMC)中乙型肝炎病毒(HBV)DNA含量,分析两者的相关性,阐述:HBV感染PBMC在乙型肝炎慢性化和向肝癌恶性转化中的作用。     

Squamous-cell carcinoma of the colon

Primary squamous-cell and adenosquamous-cell carcinoma of the colon are uncommon and their characteristics not well known. This paper reports the clinical features and pathologic findings of two colonic adenosquamous carcinomas and reviews other reports of adenosquamous and squamous carcinoma of the colon from the English medical literature. Including these two cases, 63 cases have been reported since 1927. Of these, six occurred in patients with ulcerative colitis, three occurred at the colonic opening of chronic colocutaneous fistulas, and concomitant schistosomiasis was present in two patients. Synchronous squamous-cell carcinoma of the colon was present in 3.2 percent of cases and 10 percent had either antecedent, synchronous, or metachronous adenocarcinoma of the colon. These lesions appeared to be distributed uniformly throughout the colon. The five-year survival after resective therapy for primary squamous-cell and adenosquamous-cell carcinoma of the colon calculated with life table analysis is 50 percent for Dukes' B lesions, 33 percent for Dukes' C lesions, and 0 percent for Dukes' D lesions.     

Hepatocellular carcinoma with an unusual medullary-like histology and signs of regression ("medullary-like hepatocellular carcinoma").

The case of a variant of hepatocellular carcinoma is described, which, based on its unique histology, we propose to term, medullary-like hepatocellular carcinoma. It developed in a 56-year-old male patient with liver cirrhosis, and consisted of large, amphophilic cells with a solid growth pattern. The tumour was densely infiltrated with lymphocytes and plasma cells. Lymphocytes formed a mixture of B and T cells, and plasma cells were polytypic. In addition, numerous S-100 protein-reactive stellate cells were observed at the tumour border, where marked apoptosis of hepatocellular carcinoma cells was evident. In areas of dense lymphoplasmacytic infiltration, part of the tumour cells had lost their intercellular connections and their beta-catenin reactivity. Some tumour cells expressed FasL, but not Fas. The tumour exhibited several foci of regression, showing small remnants of damaged tumour cells within dense infiltrations. The patient is alive without evidence of disease 25 months after resection. Medullary-like hepatocellular carcinoma is a lesion which mimics several features known for other medullary carcinomas, including a marked immune response which may be responsible for partial regression of this tumour.     

Hepatocellular carcinoma with an unusual medullary-like histology and signs of regression (“medullary-like hepatocellular carcinoma”)

The case of a variant of hepatocellular carcinoma is described, which, based on its unique histology, we propose to term, medullary-like hepatocellular carcinoma. It developed in a 56-year-old male patient with liver cirrhosis, and consisted of large, amphophilic cells with a solid growth pattern. The tumour was densely infiltrated with lymphocytes and plasma cells. Lymphocytes formed a mixture of B and T cells, and plasma cells were polytypic. In addition, numerous S-100 protein-reactive stellate cells were observed at the tumour border, where marked apoptosis of hepatocellular carcinoma cells was evident. In areas of dense lymphoplasmacytic infiltration, part of the tumour cells had lost their intercellular connections and their beta-catenin reactivity. Some tumour cells expressed FasL, but not Fas. The tumour exhibited several foci of regression, showing small remnants of damaged tumour cells within dense infiltrations. The patient is alive without evidence of disease 25 months after resection. Medullary-like hepatocellular carcinoma is a lesion which mimics several features known for other medullary carcinomas, including a marked immune response which may be responsible for partial regression of this tumour.     

A case of pleomorphic carcinoma of the pancreas showing sequential histological change by immunohistochemical study

Summary Pleomorphic carcinoma of the pancreas is a rare, histologically characterized pancreatic tumor with a rapid and fatal course. We report a case of a resected pleomorphic carcinoma located in the body of the pancreas in a 61-yr-old male. Histological analysis of the resected specimen revealed the coexistence of pleomorphic carcinoma with adenocarcinoma, but the recurrent tumors at autopsy 20 mo later were only of the adenocarcinomatous type. Cells in the adenocarcinomatous component showed a diffuse reactivity for CA19-9, CEA, and cytokeratin, and a focal reactivity for vimentin. In contrast, vimentin was diffusely expressed in pleomorphic lesion. Adenocarcinoma at autopsy expressed CA19-9, CEA, and cytokeratin, but not vimentin. These findings suggest that the recurrent adenocarcinoma may have developed as a consequence of sequential change in the nature of the tumor.     

Adenosquamous carcinoma of the colon

Two cases of primary adenosquamous carcinomas of the sigmoid colon and rectum are presented. Clinical features and pathologic findings of both primary and metastatic lesions are reported (including immunohistochemistry and electron microscopy). We emphasize that the presence of a metastatic squamous tumor in a patient with an unknown primary does not exclude the possibility of colonic carcinoma. Comparison with other reports in the American medical literature indicates that these are very aggressive tumors that may have a worse prognosis than the more common form of colonic adenocarcinoma. Furthermore, the squamous component, in particular, may have a greater potential for metastasizing and can do so as an undifferentiated-appearing carcinoma. In view of this, the authors suggest that very poorly differentiated areas within colonic adenocarcinomas should be very carefully evaluated by means of immunoperoxidase stains and/or electron microscopy in an attempt to identify squamous features.     

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected.     

Four immunohistochemically different primary liver cancers in one patient

We present a rare case of four immunohistochemically different primary liver cancers developing in a 54-year-old Japanese man with chronic hepatitis C. In 1989, a liver tumor had been detected at another hospital during follow-up of hepatitis C virus (HCV) infection. He was first admitted to our hospital in July 1991, when a well defined hypervascular tumor, measuring 2.5 cm in diameter was found in the S5 subsegment of the liver on computed tomography (CT); S5 subsegmentectomy was therefore performed, in July 1991. Histopathological examination revealed scirrhous hepatocellular carcinoma (SHCC). Immunohistochemical analysis showed that the tumor was negative for mouse monoclonal anti-human hepatocyte antibody (Hep), but was partially positive for a mouse monoclonal antibody specific for cytokeratin 19 (CK19). Six years after the operation, a large tumor, measuring 10 cm in diameter, was found in the S4 subsegment and a 3-cm tumor was found in the caudate lobe on CT scans. Extended left hepatic lobectomy and partial resection of the caudate lobe were performed in August 1997. Histopathological examination revealed a moderately differentiated hepatocellular carcinoma (HCC) with a trabecular pattern, an SHCC with well differentiated HCC at its periphery, and a small incidental cholangiocellular carcinoma (CCC), measuring 1 cm in diameter. The HCC and CCC showed typical immunostaining for Hep and CK19, respectively. The SHCC was positive for both Hep and CK19, showing characteristics different from those of the previously resected SHCC on immunohistochemical analysis. In conclusion, we experienced four immunohistochemically different primary liver cancers in a patient with chronic hepatitis C. Received: January 9, 2001 / Accepted: May 25, 2001 Reprint requests to: S. Ariizumi     

ERCP diagnosis of tumors in the region of the head of the pancreas

During the period 1974–1983, 320 patients with pancreas carcinoma, papilla of Vater carcinoma, bile duct bifurcation carcinoma, or duodenal carcinoma were examined by ERCP. Using 30 ERCP criteria, a radiological diagnosis was made. A valid pathological diagnosis was available in 200 patients (62.5%). In 183 of the 200 patients (91.5%), the ERCP diagnosis and the pathological diagnosis were identical. We then performed an analysis using 52 ERCP criteria. In 192 of the 200 patients (96.0%), the ERCP diagnosis based on this reanalysis and the pathological diagnosis were identical. By discriminant analysis, 13 ERCP criteria with a maximal discriminatory value were selected in patients in whom all diagnostic structures (bile ducts, pancreatic duct, and duodenum) were visible. Using these 13 criteria selected by discriminant analysis, the diagnostic score was 98.9%. A computer program based on these 13 ERCP criteria was designed for use in practice. The diagnostic accuracy of this computer program was 98.4%. Finally we tested this computer program on 171 new patients who were seen in the period 1983– 1986. In 143 of the 171 patients, a valid pathological diagnosis was available (83.6%). Comparing the ERCP diagnosis in all patients (even if not all structures were visible) with a valid pathological diagnosis, the prospective score of the computer program was 91.6%. Using this program it was possible to evaluate examinations in which not all structures were visible. When the ERCP diagnosis was uncertain, the doubt could be quantified.