肝癌首发部位对患者术后复发的影响

目的探讨肝癌首发部位及联合血清甲胎蛋白(AFP)表达对于预测肝癌患者术后复发及预后的意义。方法回顾性分析2005年3月-2009年10月行肝癌手术并长期随访的256例患者,运用Kaplan-Meier生存曲线分析总体生存率及术后复发率,Logrank检验P值,Cox比例风险模型进行单因素及多因素分析术后复发高危因素。结果肝癌首发部位不同,其术后总体生存率差异有统计学意义(P=0.022),且肝癌首发于全肝或肝左叶组患者较肝右叶组患者具有更高的术后复发风险(P=0.002)。分层分析发现,在AFP阴性(AFP<25 ng/ml)亚组中两者术后复发率差异有统计学意义(P<0.001)。Cox单因素及多因素分析显示远处转移(P=0.016)、血清AFP(P=0.002)及门脉癌栓(P<0.001)可以作为预测肝癌术后复发的独立危险因素,而肝癌首发部位不能作为一个独立的危险因素(P=0.088)。结论肝癌首发部位可以作为一个预测患者术后复发的危险因素。     

Analysis of CD4+ T-Cell responses to a novel alpha-fetoprotein-derived epitope in hepatocellular carcinoma patients.

PURPOSE: Alpha-fetoprotein (AFP) is a tumor-associated antigen in hepatocellular carcinoma and is a target for the development of cancer vaccine. Four immunodominant AFP-derived HLA-A*0201-restricted peptides have been identified and the administration of these peptides with an adjuvant has stimulated AFP-specific CTL responses in hepatocellular carcinoma patients. However, no AFP-derived CD4 T-cell epitope has yet been reported and the status of AFP-specific CD4(+) T-cell responses in hepatocellular carcinoma patients is not fully understood. The aim of this study was to analyze naturally occurring CD4(+) T-cell responses to AFP. EXPERIMENTAL DESIGN: We analyzed the ability of CD4(+) T cells to recognize an HLA-DR-restricted AFP-derived epitope in 41 hepatocellular carcinoma patients and 24 non-hepatocellular carcinoma control patients using intracellular cytokine assays for IFN-gamma. RESULTS: Here, for the first time, we report the identification of an AFP-derived CD4(+) T-cell epitope that is recognized by circulating lymphocytes from hepatocellular carcinoma patients in association with HLA-DR. The absence of detectable responses in healthy donors and patients with chronic liver disease suggests that AFP-specific CD4(+) T cells in the responder patients had been previously expanded in vivo in response to the tumor. The anti-AFP CD4(+) T-cell response was only detected in hepatocellular carcinoma patients with normal or mildly elevated serum AFP levels who were in the early stage of disease. CONCLUSION: Our data will be instrumental in the development of cancer vaccine using AFP-derived immunogens.     

Serial serum AFP heterogeneity changes in patients with hepatocellular carcinoma during chemotherapy

Summary Serum alpha fetoprotein (AFP) is heterogeneous, one form binding to the lectin concanavalin A (conA) and the other not. The relative amounts, of the two forms in the serum of patients has diagnostic applications in differentiating between primary hepato-cellular carcinoma and metastatic liver disease. In 36 patients with primary hepatocellular carcinoma, the conA-nonreactive form of AFP comprised less than 20% of the total (range 1.6%–19.2%; median 8.7%), whereas in 13 patients with metastatic liver disease the conA-nonreactive form comprised more than 20% of the total (range 26.6%–91.7%; median 57.6%).Four patients with primary hepatocellular carcinoma were treated with CB3717, and serial changes in the serum AFP characteristics were examined. In two patients in whom the total serum AFP concentration fell, the percentage of the conA-nonreactive fraction, initially less than 20% rose steadily. In two other patients the total serum AFP did not fall significantly and the proportion of the conA-nonreactive fraction remained below 20%.     

三种血清肿瘤标志物检测在原发性肝癌诊断中的意义

目的探讨恶性肿瘤相关物质(TSGF)与甲胎蛋白(AFP)、铁蛋白(SF)并用诊断原发性肝癌的临床意义.方法用化学显色法和放射免疫分析法检测40例健康人、47例急性肝炎、41例肝硬化和38例原发性肝癌血清中TSGF、AFP、SF的含量.结果 TSGF与AFP、SF联合检测的敏感性达98.4%,特异性达99.0%,阳性预测值为100%,TSGF、AFP和 SF的阳性似然比依次为8.1、10.7和5.1,阴性似然比依次为0.21、0.22和0.28.结论 TSGF与AFP、SF指标联用,可进一步提高原发性肝癌诊断的敏感性和准确性,联合检测对原发性肝癌的诊断具有十分重要的意义.     

Elevation of alpha-fetoprotein level without evidence of recurrence after hepatectomy for hepatocellular carcinoma

Seven Japanese patients showed a gradual rise in serum alpha-fetoprotein (AFP) levels for periods of 4 to 14 weeks after partial hepatectomy for hepatocellular carcinoma. These levels then gradually decreased, but not always to a normal level, and various procedures after surgery failed to detect tumor recurrence. All the cases were complicated with liver cirrhosis. It is suggested that the postoperative elevation in the AFP level may have been caused by hepatic regeneration as a result of the intervention chemotherapy and/or surgery, but it does not exclude the possibility of a tumor recurrence.     

Alpha-fetoprotein associated with islet cell tumors

Elevated serum levels of alpha-fetoprotein (AFP) (100-1,000 ng/ml) were found in three patients with islet cell tumors. Serial levels correlated with progression of disease, suggesting that AFP could be a useful tumor marker substance for islet cell tumors. Survey sera from an expanded pool of 23 patients with islet cell tumors and nine with carcinoid tumors did not identify additional cases, however, suggesting that elevated AFP levels in these classes of Apudomas are uncommon. Nonetheless, the distinction from other AFP-producing tumors such as hepatocellular carcinoma is clinically important and warrants an awareness of the rare association of AFP with these tumors.     

Evaluation of AFP glycosylation heterogeneity in cancer patients with AFP-producing tumors

It has been postulated that analysis of alpha-fetoprotein (AFP) glycosylation heterogeneity in cancer patients whose AFP levels are elevated (e.g., non-seminomatous germ cell tumors, ovarian germ cell tumors and primary hepatocellular carcinoma) might provide useful clinical information. We undertook a study to determine whether scrutiny of AFP glycosylation heterogeneity in patients with non-seminomatous germ cell tumors would provide information useful in diagnosis, staging, prognosis, or monitoring for recurrence of disease following therapy. While an analysis of AFP glycosylation heterogeneity using Concanavalin A lectin chromatography did not provide useful information in regard to staging or prognosis, it does supply unique information useful in discriminating between benign liver dysfunction (e.g. alcoholic hepatitis, chemotherapy-related liver damage) and that due to nonsemininomatous germ cell tumors. It was also concluded that an analysis of Concanavalin A binding patterns is not sufficient to discriminate between recurrent non-seminomatous germ cell tumor and primary hepatocellular carcinoma in patients with elevated serum AFP.     

An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report

A patient with primary gastric adenocarcinoma with extremely high serum alpha-fetoprotein (AFP) levels (12,000 ng/ml) is described. Histologically, foci strongly resembling hepatocellular carcinoma with hyaline globules were noted. Within tumor cells, AFP was identified with both light and electron microscopy, showing the production of AFP by tumor cells themselves. Furthermore, 88% of serum AFP combined with Concanavalin A (ConA), revealing that it was hepatic-type AFP and not germ-cell-type. Localization of alpha-1-antitrypsin within tumor cells was also noted. Ultrastructural study showed that there were two types of structures corresponding to periodic acid-Schiff (PAS)-positive globules, one of which, the proteinaceous material in intracytoplasmic lumina, was found to contain AFP. Among gastric adenocarcinomas with a high serum AFP level (several thousand or more ng/ml of AFP), foci resembling hepatocellular carcinomas have been reported by several investigators. Those gastric carcinomas, together with the current case, may constitute a clinicopathologic entity, hepatoid adenocarcinoma of the stomach.     

Hepatic tumors in Saudi Arabia. A practical approach to diagnosis

All cases of liver tumor referred to the King Faisal Specialist Hospital and Research Centre in Saudi Arabia during 2.5 years were reviewed. Hepatocellular carcinoma, 104 cases, was considerably more common than metastatic carcinoma with unknown primary, 15 cases. Lymphoma presenting as liver tumor occurred in three cases and there were no cases of cholangiocarcinoma. There were only two cases of benign tumor, both hemangioma. Hepatocellular carcinoma was characterized by a male predominance of 6:1, positive hepatitis B surface antigen in 60%, presentation with an enlarged, hard liver in over 90%, a systolic-diastolic bruit over the mass in 45%, a single highly echogenic lesion in the right lobe on ultrasound in 80%, and rapid progression. The serum AST (aspartate aminotransferase, serumglutamic oxalacetic transaminase [SGOT]) was abnormal in 97% and was higher than the alanine aminotransferase (ALT) in 93% of cases compared with 17% in 100 consecutive cases of chronic active hepatitis. Sixty-six percent of patients with hepatocellular carcinoma had serum AFP greater than 200 ng/ml. Excluding five cases of germ cell tumor (none involving the liver), and pregnant patients, serum AFP was less than 200 ng/ml in all other patients in whom it was measured between 1979 and 1981. A practical approach to the diagnosis of hepatocellular carcinoma is outlined. Biopsy does not appear to be indicated in many cases of advanced hepatocellular carcinoma.     

中性粒细胞与淋巴细胞比值在原发性肝癌诊断及预后判断中的价值

目的探讨中性粒细胞与淋巴细胞比值(NLR)在原发性肝癌诊断及预后判断中的价值。方法回顾性分析2013年1月至2015年12月解放军总医院第一医学中心收治的病理诊断为原发性肝癌的100例患者临床资料,以肝癌诊断的常规标志物血清甲胎蛋白(AFP)为对照,采用四格表诊断试验的方法分析血清NLR诊断肝癌的灵敏度和特异度,并分析其与预后的相关性。结果100例肝癌患者中,高NLR(≥1.70)者比例为56%(56/100),高于AFP阳性者比例44%(44/100),但差异无统计学意义(χ^2=2.88,P=0.08)。AFP阳性患者中,低NLR与高NLR者的中位生存时间分别为59、48个月,差异有统计学意义(χ^2=3.91,P=0.048),且高NLR是影响肝癌患者预后的独立危险因素(HR=1.232,95%CI 1.055~1.438,P=0.008)。结论NLR联合AFP检测可提高肝癌的术前诊断率。高NLR是影响原发性肝癌患者预后的独立危险因素。     

青年原发性肝癌临床特点分析

目的探讨青年原发性肝癌的临床特点.方法分析86例青年肝癌患者(年龄＜40岁)的临床特点,包括临床症状体征、肝癌家族史、饮酒史、HBV感染率、HCV感染率、ALT异常、AFP阳性、AFU阳性、合并肝硬化、门静脉癌栓以及肝癌类型,并与同期122例老年肝癌患者(年龄＞60岁)进行比较.结果青年肝癌患者占原发性肝癌患者的13.6%,在以下方面比例高于老年组,且有显著性或极其显著性差异:发热(36.0%)、HBV感染(86.0%)、ALT异常(74.4%)、AFP阳性(76.7%)、AFU阳性(81.4%)、门静脉癌栓(29.1%)和弥漫性肝癌(33.7%).结论青年肝癌恶性程度高,对HHBV感染ALT反复异常的青年人要定期进行B超和AFP检查,以便早期发现、早期治疗原发性肝癌.     

肝细胞癌高表达中期因子与肝癌细胞血行播散的关系

目的:探讨肝细胞癌(Hepatocellular Carcinoma,HCC)中期因子(Midkine,MK)蛋白高表达与肝癌细胞血行播散的可能关系.方法:应用RT-PCR和免疫组织化学染色方法分别检测AFP阳性HCC患者术前外周血AFP mRNA和手术切除肝癌组织MK蛋白,了解肝癌细胞血行播散和MK表达的情况,分析两者之间的相关性.结果:在41例HCC患者中,18例术前外周血可检出AFP mRNA,检出率为43.9%.在对应的肝癌组织中,29例高表达MK,表达率为70.7%.在29例高表达MK的HCC患者中,18例术前外周血AFP mRNA阳性,阳性率为62.1%:而在12例MK低表达的HCC患者中,仅3例术前外周血AFP mRNA阳性,阳性率为25.0%.两组之间差异有显著性(R＜0.05).结论:肝癌组织异常表达MK与外周血循环中存在肿瘤细胞有关,可能是肝癌细胞转移潜能的一个指标.     

3种肿瘤标记物联合检测对肝细胞癌切除术后再次复发的预测价值

目的：研究肿瘤标记物α-甲胎蛋白（AFP）、甲胎蛋白抑制体（AFP-L3）及脱-γ-羧基-凝血酶原（DCP）对肝细胞癌（ HCC）患者行肝切除术后复发的预测价值。方法收集行HCC肿瘤病灶根治性切除术的患者58例,考察患者的基本情况以及血清DCP、AFP及AFP-L3水平与HCC术后复发率的关系。结果术后血清AFP、DCP及AFP-L3水平均升高的患者复发率均明显提高。多因素分析结果显示：HCC患者肝切除术前血清AFP、DCP及AFP-L3联合检测与术后复发率无相关性[1．13（0．804～1．479）,P＞0．05],而术后血清AFP、DCP及AFP-L3联合检测则是影响术后复发率的独立因素[3．68（1．711～3．798）,P＜0．01]。结论血清中肿瘤标记物AFP、DCP及AFP-L3联合检测对HCC患者肝切除术后复发监测敏感有效,为HCC术后疗效评估及追踪复查提供了一条新途径。     

Serum alphafetoprotein in hepatocellular carcinoma.

The serum alphafetoprotein level (AFP) was studies in 125 histologically verified cases of hepatocellular carcinoma, 66 other malignancies, 74 cases of cirrhosis of the liver, 60 of chronic aggressive hepatitis, 12 of chronic persistent hepatitis, 16 of subacute hepatitis, 36 of acute viral hepatitis, and 13 healthy hepatitis B-surface antigen (HBsAg) carriers. Double immunodiffusion and radioimmunoassay (RIA) were used in all cases. AFP greater than 10 ng-ml appeared in 90% of the cases, and was above 400 ng/ml in 69%. In 80% of those above 400 ng/ml, AFP could also be demonstrated by immunodiffusion. The AFP level in hepatocellular carcinoma was discovered to decline as the age increased. It also appeared to be related to the tumor cell type; the relatively immature cell type was more frequently associated with a higher AFP level. The presence of HBsAg did not influence the AFP level. Although the AFP in other malignancies and liver diseases ranged abnormally from 14 to 69%, the level did not exceed 400 ng/ml as in our cases of hepatocellular carcinoma (except in one case). Thus, this figure provides a diagnostic serum level of AFP for the identification of hepatocellular carcinoma.     

肝动脉化疗栓塞结合B超无水酒精注射治疗不能切除的原发性肝癌

采用直动脉化疗栓塞结合Ｂ超引导无水酒精注射，治疗２３例不能手术切聊，直径〉３ｃｍ的原发性肝癌病人。ＴＡＥ＋ＰＥＩ组疗效优于单纯ＴＡＥ治疗组。ＴＡＥ＋ＰＥＩ组１，２，３年累计生存率分别为１００％，８４．０％和７０．０％，而ＴＡＥ组１，２，３年累计生经则为６８．２％，４２．９％和２１．５％、两组间累计生经有非常显著性差异。     

Alpha-fetoprotein production by hepatocellular carcinoma is prognostic of poor patient survival.

Immunohistochemistry using the avidin-biotin-peroxidase complex method was performed to study the production of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) tissue specimens which were obtained surgically. The relationship between staining for AFP and serum AFP levels or pathological findings was examined. The prognosis of the patients with HCC who underwent curative hepatic resections was studied with respect to the staining for AFP in their tumors. The mean serum AFP level in patients with positive AFP staining was significantly higher than in those with negative AFP staining. No significant relationship was found between AFP positivity and tumor size, tumor encapsulation, degree of vascular invasion, or the histological differentiation grade of the tumor. The patients with AFP-positive carcinomas had a poorer prognosis than did those with AFP-negative carcinomas (5-year survival rate of AFP-positive and negative groups were 26.7% and 56.5%, respectively.     

Immunoelectrophoretic Differentiation Of Alpha-Fetoprotein In Disorders With Elevated Serum Alpha-Fetoprotein Levels Or During Pregnancy

Our study aims to make differential diagnosis by immunoelectrophoresis for some common conditions with elevated levels of serum alpha-fetoprotein (AFP). One hundred and nine cases with elevated AFP levels were included in this study: yolk sac tumor (n = S), hepatocellular carcinoma (n = 26), gastric cancer (n = 12), chronic hepatitis (n = 27) and normal pregnancy (n = 36). Lectin agarose gel electrophoresis, antibody-affinity blotting, and immunoreaction were used to identify the specific patterns of AFP in the respective conditions. The results showed that there were three possible bands: L1, L2 and L3. Yolk sac tumor produced a prominent L2 band and a light L3 band. Hepatocellular carcinoma produced a prominent L1 band and a light L3 band. Gastric cancer produced only an L1 band. Chronic hepatitis had a light L1 band and a pronounced L3 band. In pregnancy, the AFP pattern is similar to that of hepatocellular carcinoma. Immunoelectrophoresis is a useful method facilitating the differentiation of AFP origins.     

Selective effects of Lipiodolized antitumor agents

Lipiodol Ultra-Fluid (Lipiodol) remains selectively in the tumor for an extended time when applied through arteries feeding the tumor. Although lipophilic antitumor drugs are selective when combined with Lipiodol, wide application of common hydrophilic agents is limited, as these compounds are insoluble in oil. We propose "Lipiodolization" of water-soluble agents using as an intermediate Urografin, a water-soluble contrast medium. Thirteen patients with primary hepatocellular carcinoma were treated with this Lipiodol-Urografin system containing antitumor agents. Marked decrease in serum alpha-fetoprotein (AFP) levels, decrease in tumor size in the hepatic imaging, and histologic studies of the resected specimen revealed this mode of therapy to be effective in 10 of 13 patients (77%) with hepatocellular carcinoma. Lipiodolization of antitumor agents is a new approach to selective cancer chemotherapy.