Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

Carcinohistogenesis and expression of alpha fetoprotein in experimental hepatocarcinoma

In1973,WhenAnthony,etal.inUganda[']werestudyinghumanhepatocirrhosisandhepatocarcinomatheyfirstreportedthatatypicalhyperplasia(AH)ofhepatocyteswasprecancerosisofhepatocellularcarcinoma(HCC).Roncalli,etal.[2]dividedAHintolargehepatocyticandsmallhepatocyticAH,andtheyconsideredthelatterwascloselyrelatedtoformingHCC.In1988,Xu,etal.[3]pointedoutthatHCCoccursfromproliferativenodulesofbasophilicandacidophilichepatocytes.Indeed,carcinohistogenesis,inparticularthechangeofalpha-fetoprotein(AFP)i…     

Low maternal serum alpha-fetoprotein levels and congenital diaphragmatic defects

We report on 2 cases of fetal congenital diaphragmatic defects with normal chromosomes among 105 patients referred for evaluation for low maternal serum alpha-fetoprotein (MSAFP) levels. The mechanism for this striking association is not clear. The association of low MSAFP levels and congenital diaphragmatic defects may have importance for MSAFP screening programs.     

Prepubertal ontogeny of responsiveness to estradiol in female rat central nervous system

The physiological response to systemic estrogens changes dramatically during the period from birth to puberty. With the onset of puberty, the rat reaches a critical developmental plateau with regard to endocrinological responsiveness to estradiol. Since the appearance of the pubertal response pattern appears to be less a consequence of some intrinsic “trigger” than the natural continuation of a developmental sequence that begins prenatally, its ontogeny should be examined in a broad context that will take account of the impact of each of the dynamic components influencing the interactions between estradiol and the central nervous system on the functional development of the organism as a whole. The prepubertal ontogeny of endocrinological responsiveness to estradiol in the central nervous system of the female rat is examined in the context of several of the important factors that are known to influence the functional development of the hypothalamo-pituitary-gonadal circuit: the rapidly changing hormonal environment of the morphologically and physiologically immature juvenile rat, the shifting predominance of alphafetoprotein and “adult” estradiol-binding protein, sexual differentiation of the neural substrate, and the development of mature pituitary-gonadal feedback machanisms. The availability of ever more sensitive techniques for the measurement of the actions of estradiol in the central nervous system of the immature organism has necessitated a re-evaluation of existing data. This, in turn, suggests that new approaches should be applied to the examination of problems related to the development of reproductive maturity of the central nervous system.     

Diagnostic accuracy of tumor markers for hepatocellular carcinoma: a systematic review

Background and aims The role of alphafetoprotein (AFP) in the diagnosis and surveillance of hepatocellular carcinoma (HCC) is getting smaller owing to the advances in imaging modalities. The aims of this study were to assess the diagnostic accuracy of tumor markers in small HCC and to find the optimal cutoff value of each tumor marker for efficient surveillance. Methods Studies in all languages were identified by searching MEDLINE from 1982 to 2002. Studies were included when they showed sensitivity and specificity for HCCs 5 cm or smaller and recruited only patients with chronic hepatitis or liver cirrhosis as control. We assessed diagnostic odds ratios (DORs) for the evaluation of diagnostic accuracy of tumor markers and positive likelihood ratios (LRs+) to find the optimal cutoff value. DORs and LRs+ were combined according to the random effect model. The summary receiver operating characteristics (ROC) curve was also assessed. Results Seventeen articles on three tumor markers—AFP, des-gamma-carboxyprothrombin (DCP), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3)—were enrolled after full-text evaluation. AFP was inferior to DCP and AFP-L3 in both DOR (4.50 vs. 8.16 and 10.50) and area under the ROC curve (0.647 vs. 0.688 and 0.695). Optimal cutoff values that provide the best LR+ were 200 ng/ml for AFP, 40 mAU/ml for DCP, and 15% for AFP-L3. Conclusions Diagnostic accuracy of AFP in small HCC was substantially limited. Surveillance including other tumor markers with optimal cutoff value should be conducted to confirm the efficacy of the policy. This study was supported by the Ministry of Health, Labour and Welfare in Japan (H14-Iryo-032).     

中山市小榄镇肝癌高发现场筛查评估及问题分析

目的 通过对高发区肝癌筛查现场的评估,了解筛查对象乙型肝炎表面抗原（hepatitis B surface antigen, HBsAg）阳性人群分布特征,并进一步分析筛查检出肝癌患者情况。方法 应用ELISA法检测血清HBsAg和甲胎蛋白（alpha-fetoprotein, AFP）,B型超声进行腹部脏器检查。结果 （1）筛查人群HBsAg阳性率为15.7%（2 889/18 460）,其中男性阳性率高于女性（P=0.000）。男女人群HBsAg阳性率均随年龄的增长呈降低趋势（P＜0.01）。（2）HBsAg阳性（肝癌高危）人群中初筛和随访分别检出肝癌11例和5例,早诊率分别为27.3%（3/11）和40%（2/5）。整个筛查队列两年共漏诊肝癌11例,其中4例源于高危人群自行退出随访,7例出自HBsAg阴性人群,漏诊的肝癌分别占相应人群总肝癌的20%（4/20）和25.9%（7/27）。（3）高危人群和一般人群组肝癌发病率分别为346.1/10万（20/5 778）和49.9/10万（37/74 084）,前者发病率高于后者（P＜0.05）。高危人群组和一般人群组肝癌早诊率分别为30.0%（6/20）和8.1% （3/37）,两者比较差异无统计学意义（P＞0.05）。高危人群组肝癌患者半年、1年和2年生存率分别高于一般人群组中肝癌患者（P＜0.05）。结论 在肝癌高发区进行筛查,了解人群HBsAg分布特征,筛选出高危人群,能及时发现肝癌患者,提高近期生存率。然而,HBsAg阴性人群和依从性差的高危人群中有一定的漏诊率,肝癌筛查的早诊率和生存率仍有待提高。     

In vivo uptake of heterologous alphafetoprotein and serum albumin by ependymal cells of developing chick embryos

The in vivo uptake by neuroepithelial cells of rat serum proteins injected into the mesencephalic cavity of developing chicken was demonstrated by immunohistochemical methods. It was found that 48 h after inoculation, rat alphafetoprotein (AFP) and serum albumin (SA) localize in the same places as do chicken AFP and SA. No labelling was present for rat or chicken IgG. We also present evidence showing that chicken ovalbumin, which is not normally found inside ependymal cells is not internalized even when injected into the cerebrospinal fluid at 30-fold its physiological concentration. The existence of transient specific receptors which could be responsible for this protein uptake is proposed. The possible implications in relation to developmental biology are discussed.     

血清AFP、GGT、SF联合检测在原发性肝癌诊断中的价值

目的探讨联合检测血清甲胎蛋白（AFP）、γ-谷氨酰基转移酶（GGT）、铁蛋白（SF）在原发性肝癌诊断中的价值。方法检测61例原发性肝癌患者、64例肝炎／肝硬化患者和55例健康对照组血清AFP、GGT、SF的含量。结果AFP和SF检测的阳性率在原发性肝癌组与肝炎／肝硬化组比较差异具有统计学显著意义（P〈0．05）,肝癌组的阳性率高于肝炎／肝硬化组,GGT检测的阳性率在两组比较差异元统计学意义（P〉0．05）;AFP、GGT和SF三项联合检测原发性肝癌的阳性率可提高到96．7％,与单项检测比较差异均具有统计学显著意义（P〈0．05）。结论血清AFP、GGT、SF联合检测可明显提高对原发性肝癌的阳性检出率。     

AFP RIA结果分析计算机专家系统（ARA）的开发

为了探索计算机技术在放免结果分析中的应用。用ＶＰ－ＥＸＰＥＲＴ专家系统开发软件开发了ＡＦＰ结果分析专家系统（ＡＲＡ），经临床初步试用，诊断符合率为８２．３％。     

Is anti-alphafetoprotein immunoscintigraphy a promising approach for the diagnosis of hepatoma?

The actual interest of immunoscintigraphy for the detection of liver tumours was investigated by both visual examination and quantitative analysis in 41 patients with hepatoma (HCC, 21 cases, 13 AFP-secreting), other primary or secondary liver cancer (9 cases), testicular cancer (2 cases) and cancer free cirrhosis (9 cases). All patients were injected with ¹²³I-anti-alphafetoprotein (AFP) monoclonal antibodies (MAbs) and scans were performed after 28±2 h. In the hepatoma-bearing patients, 11 positive anti AFP scans were found; 9 of them had an enhanced serum; besides, 3 non HCC tumours were also detected. With respect to hepatoma diagnosis, sensitivity was 52.5% and specificity 66.5%. For all hepatomas, it was striking that the positivity rate was 2/10 and 9/11, respectively, when HCC was and was not associated with cirrhosis. Among 6 patients with a positive anti AFP scan who were also injected with control anti hCG ¹²³I-MAb, 5 positive anti hCG scans were surprisingly found, with specificity indices ranging between 1.00 and 1.75. The quantitative study also highlighted the importance for hepatoma detection of specific and non specific factors such as serum AFP, tumoural vascularization, non tumoural liver uptake and intrahepatic distribution of HCC.Anti AFP immunoscintigraphy appears as a poorly sensitive and moderately specific method for hepatoma diagnosis. In contrast, non tumoural liver uptake level could be more useful for discriminating HCC from liver metastases and perhaps to detect the early extension of HCC.This work was partly supported by the ARC grant nr 6265