AFP阳性肝细胞癌的诊断标准

目的评价甲胎球蛋白阳性＋肝实质占位病变＝肝细胞癌的诊断标准．方法本院１９８９年～１９９４年１０３３例ＡＦＰ阳性，明确诊断的住院患者进行回顾分析，所有患者分成两组即肝占位病变组７３０例，非肝占位病变组３０３例．ＡＦＰ的阳性标准＞３１μｇ／Ｌ．结果肝占位病变组、ＡＦＰ＞２００μｇ／Ｌ者６２０例，＞３１μｇ／Ｌ但＜２００μｇ／Ｌ者１１０例．非肝占位病变组，１８８例ＡＦＰ＞２００μｇ／Ｌ，１１５例ＡＦＰ＞３１μｇ／Ｌ但＜２００μｇ／Ｌ．ＡＦＰ＞２００μｇ／Ｌ伴肝ＳＯＬ肝细胞癌的发病率占９８１％，其它恶性肿瘤占０８％．ＡＦＰ＜２００μｇ／Ｌ伴肝ＳＯＬ者，ＨＣＣ符合率占５９１％，肝良性占位占３４５％，按诊断标准（ＡＦＰ＞２０μｇ／Ｌ），有１／３肝良性占位病变被误诊为ＨＣＣ．结论对ＡＦＰ升高的患者应针对病情全面、综合分析．当肝ＳＯＬ存在时，用ＡＦＰ＞２００μｇ／Ｌ作为诊断ＨＣＣ的标准较合适．     

血清AFP GGT及ALP联检对肝细胞性肝癌的诊断价值

血清ＡＦＰＧＧＴ及ＡＬＰ联检对肝细胞性肝癌的诊断价值辛召平闻勤生赵永锋第四军医大学唐都医院消化科陕西省西安市７１００３８Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒｎｅｏｐｌａｓｍｓ／ｂｌｏｏｄ；ｃａｒｃｉｎｏｍａ，ｈｅｐａｔｏｃｅｌｕｌａｒ／ｂｌ...     

应用逆转录聚合酶链反应检测原发性肝癌患者外周血肿瘤细胞

目的寻求检测循环血中肝癌细胞的灵敏方法。方法采用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）技术，对肝癌患者外周血有核细胞人甲胎蛋白ｍＲＮＡ（ＡＦＰｍＲＮＡ）进行检测。结果３１例原发性肝癌中有１５例检出ＡＦＰｍＲＮＡ，阳性率为４８．４％。良性肝病、肝转移癌患者和健康对照组均为阴性。外周血细胞ＡＦＰｍＲＮＡ的存在与肝内转移、门静脉癌栓和远处转移密切相关。结论外周血细胞ＡＦＰｍＲＮＡ是反映原发性肝癌患者有无血行播散的重要标志，ＲＴ－ＰＣＲ技术是检测循环血中原发性肝细胞癌的灵敏方法     

代谢组学在肝细胞癌标志物研究中的应用

代谢组学技术作为一种新的组学研究手段,能够揭示肝细胞癌(HCC)发生发展过程中的代谢谱差异,成为HCC生物标志物研究的热点。简述了代谢组学在HCC诊断中的意义,概括了HCC相关的生物标志物的代谢组学研究,这些研究主要以血清、尿液及肝组织代谢物为对象,通过动物实验和临床研究两个方面进行。指出分析和监视HCC发生发展过程中相应代谢物的变化,对于患者的个体化治疗具有重要价值。     

原发性肝癌的MRI表现

肝细胞癌（ＨＣＣ）占肝脏原发恶性肿瘤的８０％以上［１］．ＭＲＩ具有很高的组织分辨率、多参数、多方位成像等特点,成为继ＣＴ之后的又一有效而无创伤性的肝癌检查诊断方法,我们收集３０例经证实的ＨＣＣ患者的ＭＲＩ资料,采用双盲法进行前瞻性回顾分析,旨在探讨Ｍ...     

原发性肝癌MRI特征

目的探讨原发性肝癌的ＭＲＩ特征，以提高诊断准确性．方法原发性肝癌２９例，全部为男性，年龄３３岁～８０岁，平均５６岁．ＧｄＤＴＰＡ增强扫描１０例共１１个肿块．扫描序列为自旋回波（ＳＥ）、ＦＬＡＳＨ，扫描层厚８ｍｍ～１０ｍｍ．结果肿瘤不规则６９２％（３６／５２），边缘模糊３８５％（２０／５２），长ＴＥ肿瘤的信号强度增高不明显．假包膜征１９例，Ｔ１ＷＩ表现为低信号单环，Ｔ２ＷＩ为低信号或高信号单环，典型表现为外高内低双环．１５例镶嵌征Ｔ１ＷＩ和Ｔ２ＷＩ表现为肿瘤内线样或不规则低信号区．１３例斑征Ｔ２ＷＩ表现为肿瘤内高信号斑块．动态增强扫描肿瘤中心不规则强化３６４％，肿瘤边缘结节样强化４５５％．门静脉或下腔静脉瘤栓是原发性肝癌的辅助征象．结论原发性肝癌ＭＲＩ具有特征性．     

中国肝癌临床研究进展

我国２７个省１９９０／１９９２抽样调查表明，肝癌在癌症死亡率中已上升为第二位，达２０３７／１０万，其中男性２９０１／１０万，女性１１２１／１０万［１］．我国肝癌的主要病因因素有：病毒性肝炎感染－我国肝癌患者中约９０％有乙型肝炎病毒（ＨＢＶ）感染...     

膨胀型和浸润型肝细胞癌超微结构的比较

目的了解膨胀型肝癌（ＥＨＣＣ）的超微结构与其生物学特性的关系．方法用透射电镜对ＥＨＣＣ和ＩＨＣＣ（浸润性肝癌）各２０例对比观察．结果全部４０例肝癌分为３组：分化较成熟型ＥＨＣＣ（１６例），分化未成熟型ＥＨＣＣ（４例），分化未成熟型ＩＨＣＣ（２０例）．分化较成熟型ＥＨＣＣ的超微形态和癌周肝组织相似，其特点为：癌细胞质膜发育较好；核规则圆形、核膜平滑；核仁圆形实心唯体积肥大；细胞器丰富、发育较好．而分化未成熟型ＥＨＣＣ和ＩＨＣＣ的超微形态，与癌周肝组织差异显著，其特点为：癌细胞质膜发育不良；核形不规则，畸形核显著，核膜不平滑，假包含体众多；核仁巨大畸形；细胞器大多肿胀变性．结论ＥＨＣＣ的大多数（８０％）为分化较成熟型，少数为分化未成熟型．癌细胞分化较好，可能是该型生长缓慢并呈膨胀型生长的原因之一．但该型具有较强的潜在侵袭性和向浸润型转化的倾向．     

血清肿瘤标志物联合检测对消化系恶性肿瘤的诊断价值

目的探讨多项肿瘤标志物联合检测对诊断消化系恶性肿瘤的实用价值．方法选择经临床确诊的消化系恶性肿瘤１１９例，其中原发性肝癌２５例，胰腺癌２１例，胃癌２９例，大肠癌２７例，其他消化系恶性肿瘤１７例，以及同期良性消化系疾病５６例，应用ＲＩＡ或ＥＬＩＳＡ法检测血清ＣＥＡ，ＡＦＰ，ＳＦ，β２ＭＧ，ＣＡ１９９及ＣＡ５０水平．由实验室参考药盒厂家提供的正常值及实验室所做的正常人群均值，确立各项检测正常上限值，样品超过界值为阳性，反之为阴性．结果肝癌组以ＡＦＰ敏感度最高（６８０％），联合ＳＦ和ＣＡ１９９可提高至９２０％．胰腺癌组ＣＡ１９９最敏感（７６２％）．应用ＣＡ１９９，ＳＦ和ＣＡ５０联合检测，敏感度可达８５７％和９５２％．对胃癌和大肠癌，即使６项联合也不足８０％．结论联合检测对肝癌和胰腺癌可明显提高阳性率，但对胃癌及大肠癌仅起部分辅助作用．联合检测既提高灵敏度，也降低特异度．     

肝细胞癌诊断标志物的研究进展

肿瘤标志物,又称为生物标志物,主要由肿瘤或宿主产生,能在体液或组织中检测到并有助于诊断和鉴别肿瘤。通过测定其存在或含量可辅助肿瘤的早期诊断、分子分型、分析病程、指导治疗、监测复发或转移及判断预后等。理想的标志物一般应敏感性高,能早期测出所有肿瘤患者,同时可用于以下一种或多种情况：早期诊断;筛检高危人群;监测病程进展与疗效、早期复发和转移或指导化学治疗的终点时间。     

Role of circulating tumor cells and cancer stem cells in hepatocellular carcinoma

Circulating tumor cells (CTC) and cancer stem cells (CSC) have been proposed as tools for detection and characterization of disease and individualization of therapy in patients with many solid tumors. Several automated and semi-automated techniques for identification and isolation of these cells from blood have been proposed and reviewed mostly focusing on their feasibility. In this mini review we summarize the recent relevant literature on this topic and discuss the clinical usability of measuring CTC and CSC in peripheral blood in patients with hepatocellular carcinoma (HCC). Besides literature, the basis for this evaluation was the authors’ experience with treating HCC and research experience on CSC and CTC. Few original reports and reviews have been published focusing on CTC and CSC in HCC. Though HCC is one of the five most common malignancies worldwide only recently these cells have come into focus for detection and characterization of this disease that is characterized by high plasticity and malignancy. A focused and prospective validation of the clinical usability of detecting these cells in HCC is still needed, but results seem promising that they may add great benefit for early detection and individualization of therapy.     

Significance of circulating endothelial progenitor cells in hepatocellular carcinoma

This study evaluated the significance of circulating bone marrow-derived endothelial progenitor cells (EPCs) in patients with hepatocellular carcinoma (HCC), a solid tumor with rich neovasculature. Eighty patients with HCC were recruited for the study, and 16 patients with liver cirrhosis and 14 healthy subjects were also included for comparison. Blood samples were taken before treatment. Total mononuclear cells were isolated from peripheral blood, preplated to eliminate mature circulating endothelial cells, and colony-forming units (CFUs) formed by circulating EPCs were counted. To validate the CFU scores, FACS quantification of EPCs using CD133, VEGFR2, and CD34 as markers was performed in 30 cases. Our study showed significantly higher mean CFU scores in patients with HCC compared to patients with cirrhosis and healthy controls (P = .001 and .009, respectively). Furthermore, the CFU scores of patients with HCC positively correlated with levels of serum alpha-fetoprotein (r = .303, P = .017), plasma VEGF (r = .242, P = .035), and plasma interleukin-8 (IL-8) (r = .258, P = .025). Patients with unresectable HCC had higher CFU scores than patients with resectable tumors (P = .027). Furthermore, for those who underwent curative surgery, higher preoperative CFU scores were observed in patients with recurrence within 1 year compared with those who were disease-free after 1 year (P = .013). In conclusion, higher circulating levels of EPCs are seen in patients with advanced unresectable HCC as compared to patients with resectable HCC or those with liver cirrhosis. Our evidence supports the potential use of circulating level of EPCs as a prognostic marker in patients with HCC.     

Improved method increases sensitivity for circulating hepatocellular carcinoma cells

AIM:To improve an asialoglycoprotein receptor(ASGPR)-based enrichment method for detection of circulating tumor cells(CTCs)of hepatocellular carcinoma(HCC).METHODS:Peripheral blood samples were collected from healthy subjects,patients with HCC or various other cancers,and patients with hepatic lesions or hepatitis.CTCs were enriched from whole blood by extracting CD45-expressing leukocytes with monoclonal antibody coated-beads following density gradient centrifugation.The remaining cells were cytocentrifuged on polylysine-coated slides.Isolated cells were treated by triple immunofluorescence staining with CD45antibody and a combination of antibodies against ASGPR and carbamoyl phosphate synthetase 1(CPS1),used as liver-specific markers,and costained with DAPI.The cell slide was imaged and stained tumor cells that met preset criteria were counted.Recovery,sensitivity and specificity of the detection methods were determined and compared by spiking experiments with various types of cultured human tumor cell lines.Expression of ASGPR and CPS1 in cultured tumor cells and tumor tissue specimens was analyzed by flow cytometry and triple immunofluorescence staining,respectively.RESULTS:CD45 depletion of leukocytes resulted in a significantly greater recovery of multiple amounts of spiked HCC cells than the ASGPR+selection(P s<0.05).The expression rates of either ASGPR or CPS1were different in various liver cancer cell lines,ranging between 18%and 99%for ASGPR and between 9%and 98%for CPS1.In both human HCC tissues and liver cancer cell lines,there were a few HCC cells that did not stain positive for ASGPR or CPS1.The mixture of monoclonal antibodies against ASGPR and CPS1identified more HCC cells than either antibody alone.However,these antibodies did not detect any tumor cells in blood samples spiked with the human breastcancer cell line MCF-7 and the human renal cancer cell line A498.ASGPR+or/and CPS1+CTCs were detected in 29/32(91%)patients with HCC,but not in patients with any other kind of cancer or any of the other test subjects.Furthermore,the improved method detected a higher CTC count in all patients examined than did the previous method(P=0.001),and consistently achieved 12%-21%higher sensitivity of CTC detection in all seven HCC patients with more than 40 CTCs.CONCLUSION:Negative depletion enrichment combined with identification using a mixture of antibodies against ASGPR and CPS1 improves sensitivity and specificity for detecting circulating HCC cells.     

联合治疗复发性肝癌血液循环性肝癌细胞的变化及意义

目的：探讨联合经肝动脉插管化疗栓塞术（TACE）及无水酒精瘤内注射术（EPI）治疗复发性肝癌周围静脉血液循环性肝癌细胞的变化及其意义,方法：应用巢式RT－PCR检测19例复发性肝癌患者而血液循环性肝癌细胞,并经TACE及PEI联合治疗观察其血液循环性肝癌细胞的变化。结果：血液循环性肝癌细胞表达阳性的7例复发性肝癌患者（36．8％）,经TACE及PEI联合治疗后其血液循环性肝癌细胞均转有阴性（100％,,0．01）.结论：联合TACE及PEI治疗复发性肝癌可有效地杀灭血液中播散的循环性肝癌细胞,可预防肝癌再复发和转移的发生。     

HS-GGT和AFP-mRNA联合分析在肝癌诊断中的临床价值

目的　探讨肝癌特异性γ 谷氨酰转移酶 (HS GGT)和AFP mRNA联合分析在肝癌诊断中的临床价值。方法　从肝癌患者外周血有核细胞中提取总RNA ,以逆转录聚合酶链反应 (RT PCR)扩增分析AFP mMNA ,同时定量分析患者血HS GGT水平 ,比较它们在肝癌诊断中的临床价值。结果　所设计RT PCR扩增AFP基因片段大小为 15 9bp ,肝癌患者外周血AFP mRNA阳性率为60 3 % ,显著高于急性肝炎、慢性肝炎、肝硬化、肝外肿瘤及正常对照组 (P <0 0 1)。另外 ,AFP mRNA阳性率 ,在AFP浓度低于 5 0ng/ml肝癌组中为 5 7 1% ,在伴肝外转移的肝癌组中全数阳性。AFP mRNA阳性与肿瘤大小间无明显相关性 ,与HS GGT联合分析诊断肝癌的总阳性率达 93 6% 结论　HS GGT定量和外周血AFP mRNA分析有助于肝癌诊断、远处转移或术后复发的监测     

射频消融对复发性肝细胞癌外周血循环肿瘤细胞的影响

目的:探讨射频消融术治疗复发性肝细胞癌对外周血肝癌细胞的影响.方法:分别采集23例复发性肝细胞癌患者射频消融治疗前、后和5位健康对照者外周血,免疫磁珠技术分离血中游离肝癌细胞,常规病理和AFP免疫组化染色验证分离到的肝癌细胞.结果: 23例复发性肝癌患者,术前外周血肝癌细胞阳性15例(65.22%),射频消融治疗1次后第1、3天,外周血肝癌细胞阳性分别为13例(56.52%)和6例(26.09%).射频消融治疗前和治疗后1 d的阳性率比较,差异无统计学意义;而治疗前和治疗后3 d、治疗后1 d和3 d的阳性率比较,差异均有统计学意义(P<0.05).结论:射频消融治疗复发性肝癌可以有效地预防或阻止肝癌血行播散.     

Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer

The clinical impact of circulating tumor cell (CTC) detection is controversial, mainly due to drawbacks of molecular approaches applied to this field. We sought to determine if the specific identification and counting of circulating tumor cells by cytomorphologic analysis has clinical usefulness. Peripheral blood (6 mL), treated using isolation by size of epithelial tumor cells, was obtained from 44 patients with primary liver cancer (PLC) and without metastases, 30 patients with chronic active hepatitis, 39 with liver cirrhosis, and 38 healthy individuals, and followed up for a mean period of 1 year. We searched for beta-catenin mutations in 60 single microdissected CTCs. One patient with liver cancer developed extrahepatic metastases during follow-up. CTCs and microemboli were found in 23 of the 44 patients with liver cancer and in none of the patients with chronic active hepatitis, patients with cirrhosis, or healthy subjects. Their presence was significantly associated with tumor diffusion (P =.0001) and portal tumor thrombosis (P =.006). Both the presence (P =.01) and number (P =.02) of CTCs and microemboli were significantly associated with a shorter survival. Beta-catenin mutations were found in 3 of 60 CTCs, arguing against their impact on the initial step of tumor cell invasion. In conclusion, the highly sensitive and specific detection of CTCs and microemboli may have clinical implications for cancer staging and outcome prediction. We also show the feasibility of molecular studies of individual circulating tumor cells, aimed at identifying gene mutations involved in tumor invasion.