高尔基体蛋白73联合甲胎蛋白异质体在原发性肝癌诊断中的价值

目的探讨高尔基体蛋白73(GP73)与甲胎蛋白异质体(AFP-L3)联合检测在乙型肝炎病毒相关性肝癌诊断中的价值。方法收集132例血清,其中原发性肝癌(PHC)56例、肝硬化33例,慢乙肝患者23例,健康对照20例,酶联免疫吸附法(ELISA)检测各组GP73的表达情况;应用甲胎蛋白异质体亲和吸附离心管洗脱获得AFP-L3,同时化学发光法检测原始血清中总AFP和AFP-L3,计算AFP-L3在总AFP中的比率。结果 PHC组、肝硬化组、肝炎组及健康对照组血清GP73水平分别为247.05(228.35～287.72)、176.83(159.51～183.98)、152.58(135.19～162.85)、43.00(37.96～52.64)ng/mL,AFP-L3%分别为14.52(12.33～15.28)%、5.68(4.32～7.74)%、4.31(3.57～6.45)%、3.29(2.60～4.25)%。PHC组GP73和AFP-L3%均明显高于其他组(P均<0.01);GP73和AFP-L3%用于诊断PHC的ROC曲线下面积分别为0.825、0.828,最佳截取值分别为187.60 ng/mL、9.98%,此时的敏感度分别为69.6%、64.3%,特异度分别为86.8%、96.1%。二者联合诊断PHC的敏感度为82.1%,特异度为85.5%。结论 GP73和AFP-L3%均可作为诊断PHC的血清标记物,二者联合检测具有更高的灵敏度,可提高PHC的诊断率。     

Increased amnionic fluid alpha-fetoprotein due to a holoacardium amorphous twin

Amnionic fluid alpha-fetoprotein measurement was employed as a screening test for neural tube defects in a pregnancy only at risk due to advanced maternal age. The alpha-fetoprotein concentration was elevated more than 10 standard deviations above the mean and was found to be caused by a holoacardium amorphous twin. A normal female fetus was also present. Various causes of elevated alpha-fetoprotein concentration in amnionic fluid are discussed.     

Hepatocellular Carcinoma Containing Endocrine CelIs: An Autopsy Report of Triplecancer Involving the Liver, Kidney and Thyroid

An autopsy case of triplecancer (hepatocellular carcinoma of the liver, renal cell carcinoma of the kidney, and papillary carcinoma of the thyroid) was reported. Histological features of primary hepatic tumor suggested undiffer-entiated hepatocellular carcinoma (Edmondson Steiner's Grade IV). However, certain tumor cells showed distinctive argyrophilic reactions and electron microscopy revealed small round granules resembling electron dense endocrine secretory granules in their cytoplasm. Immuno-histochemistry demonstrated that tumor cells showed a positive reaction for AFP while some others were positive for chromogranin A. lmmunohistochemical demonstration of AFP production by tumor cells indicated their he-patocyte origin. No endocrine syndrome had been present and no alternative primary source of the endocrine tumor was detected. Tumors of the kidney and thyroid were considered to be incidentally combined. Acta Pathol Jpn 42: 904–910, 1992.     

Prenatal diagnosis of polycystic kidneys and encephalocele (Meckel syndrome)

Two unrelated families are presented with repeated occurrences of a congenital syndrome of which the main stigmata were polycystic kidneys and occipital encephalocele (Meckel syndrome). Prenatal diagnosis, followed by interruption of pregnancy, was performed in one case. The diagnosis was based on an increase of amniotic alpha-fetoprotein (AFP), and on the mode of growth and cell types of cultured amniotic cells. In another similarly examined case the diagnosis was suspected, but the parents did not wish the pregnancy to be interrupted. The child was stillborn and malformed. AFP values are presented and discussed in relation to the observed malformations. Neural tube defects are associated with an increase of AFP in amniotic fluid, but, as in normal pregnancies, the values decrease with increasing gestational age. On the other hand, kidney malformations seem to be associated with AFP values which remain high or even increase with increasing gestational age.     

Concanavalin A reactivity pattern of human amniotic fluid AFP examined by crossed affino-immunoelectrophoresis. A definite test for neural tube defect?

The percentage of alpha-fetoprotein (AFP) not reacting with concanavalin A (con A) was determined by crossed line affino-immunoelectrophoresis in amniotic fluid from 25 pregnancies with neural tube defects (NTD) and other fetal abnormalities giving rise to elevated AFP levels, and from 128 pregnancies with normal outcome. The percentage of con A non-reactive AFP is significantly lower in the presence of fetal abnormalities (mean 3.4 %, range: 0.0–6.3, n = 23, compared to the percentage found in normal pregnancies (mean 17.2 % , range: 6.6–35.8 %, n = 128). In amniotic fluid samples from normal pregnancies, the percentage of con A non-reactive AFP in 84 cases with total AFP levels lying within the 95 % reference interval was not significantly different from the percentage found in 44 cases with levels above the 95 % reference interval. The percentage of non-reactive AFP in fetal serum and cerebrospinal fluid was of the same magnitude as found in amniotic fluids of pregnancies with fetal abnormalities. It is concluded that analysis of the percentage of con A non-reactive AFP by crossed line affino-immunoelectrophoresis is a simple, reliable and apparently diagnostic test for NTD and ether abnormalities with leakage of fetal serum or cerebrospinal fluid into the amniotic fluid. The test should therefore be used in all cases with only marginally elevated AFP levels, so false positives may be avoided.     

Primary Adenocarcinoma of the Female Urethra with Three Histologic Patterns and Partial AFP Positivity

A rare case of adenocarcinoma of the female urethra with alpha-fetoprotein (AFP) positivity in a 52-year-old woman is reported. The tumor was papillary polypoid, localized in the posterior wall of the mid-urethra and microscopically showed three histologic components. Upon immunostain-ing and histochemical staining, the tumor was characterized by intestinal type cells positive for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), EMA negative and AFP positive columnar vacuolated cells and mainly EMA positive clear cells. On the basis of these features together with the known embryogenesis of the urethra, an endodermal origin of the tumor is suggested, possibly arising from the reserve or stem cells in the urethral mucosa. This case and its immunohistochemical features are quite unique and the histologic combination is meaningful when considering the oncogenesis and histogenesis of urethral tumors. Acta Pathol Jpn 40: 838 844, 1990.     

High burden of hepatocellular carcinoma and viral hepatitis in Southern and Central Vietnam: Experience of a large tertiary referral center, 2010 to 2016

AIM To examine the largest tertiary referral center in southern and central Vietnam from 2010 to 2016, evaluating epidemiological trends of hepatocellular carcinoma(HCC) and viral hepatitis B-C in this resource-limited setting.METHODS We extracted data of patients receiving care from Cho Ray Hospital(Ho Chi Minh City), the largest oncology referral center in southern and central Vietnam, from 2010 to 2016. We collected information on patient age, gender, geographic distribution, and disease characteristics including disease stage, tumor biomarker levels [serum alpha-fetoprotein(AFP), AFP-L3 isoform percentage, and prothrombin induced by induced by vitamin K absence-Ⅱ], and serological testing for hepatitis B virus(HBV) and hepatitis C virus(HCV) infections.RESULTS Data from 24091 HCC patients were extracted, with sample demographics comprising mostly male(81.8%) and older age(however with 8.5% younger than 40 years old). This patient sample included a geographic catchment population of 56 million people(60% of the country's total population of 92.7 million), derived from 38 provinces and municipalities in Vietnam. Chronic HBV infection was found in 62.3% of cases, and chronic HCV infection in 26.0%. HBV and HCV co-infection was seen in 2.7%. Cirrhosis was found in an estimated 30% to 40% of cases. Nine percent of patients were not found to have chronic viral hepatitis. Twenty three point two percent of the patients had a normal AFP level. A total of 2199 patients were tested with AFP-L3 and PIVKA Ⅱ over two years, with 57.7% having elevated AFP-L3%, and 88.5% with elevated PIVKA Ⅱ levels. Over this 7-year period, the incidence of HCC increased, with a large proportion of cases(overall 40.8%) presenting initially an advanced stage, not amendable to surgical or locoregional therapy.CONCLUSION HCC contributes significant health care burden in southern and central Vietnam, with increasing case volume over this seven-year period. Viral hepatitis likely explains this high HCC prevalence.     

Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal,high and very high preoperative alpha-fetoprotein levels

AIM To investigate the impact of alpha-fetoprotein(AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patient survival.METHODS Data of adult patients who received liver transplant(LT) for hepatocellular carcinoma(HCC) at our hospital from January 2000 to December 2013 were reviewed. Reviewed data included demographic characteristics, preoperative AFP level, operative details, follow-up details, and survival outcomes. Patients were mostly listed for LT based on Milan or UCSF criteria. For the purpose of this study, normal AFP level was defined as AFP value 10 ng/m L, high AFP level was defined as AFP value ≥ 10 to 400 ng/m L, and very highAFP level was defined as AFP ≥ 400 ng/m L. The patients were divided into these 3 groups accordingly. Survival rates were plotted as Kaplan-Meier curves and compared by log-rank analysis. Continuous variables were expressed as median(interquartile range). Categorical variables were compared by Spearman's test. Discriminative analysis was used to define the lowest value of AFP that could affect the overall survival in study population. Statistical significance was defined by a P value of 0.05.RESULTS Totally 250 adult patients underwent LT for HCC in the study period. Eight-four of them received deceaseddonor LT and 166 had living-donor LT. The patients were divided into 3 groups: Group A, AFP 10 ng/m L(n = 83); Group B, AFP ≥ 10 to 400 ng/m L(n = 131); Group C, AFP ≥ 400 ng/m L(n = 36). The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar(median, 13 vs 13 vs 12; P = 0.745). The time to operation in Group A was longer(median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality(P = 0.626) and postoperative complication(P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, but the tumors in Group C were larger(A: 2.5 cm, B: 3.0 cm, C: 4.0 cm; P = 0.003). Group C had a bigger proportion of patients who were beyond Milan criteria(P = 0.010). Poor differentiation and vascular permeation were also more common in this group(P = 0.017 and P = 0.003 respectively). It also had poorer 5-year survival(A: 85.5%, B: 82.4%, C: 66%; P = 0.029). The 5-year disease-free survival was 84.3% in Group A, 80.1% in Group B, and 61.1% in Group C. Receiver operating characteristic area under the curve for AFP in predicting tumor recurrence was 0.685. The selected cut-off value was 54 ng/m L for AFP(C-index 0.685; 95%CI: 0.592-0.779; sensitivity 0.595; specificity 0.687). On discriminative analysis, AFP value of 105 ng/m L was shown to affect the overall survival of the patients.CONCLUSION HCC patients with a high preoperative AFP level had inferior survival after LT. AFP level of 54 ng/m L was associated with disease recurrence, and AFP level of 105 ng/m L was found to be the cut-off value for overall survival difference.