Alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 19-9-producing gallbladder cancer

We report a rare case of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9-producing gallbladder cancer with high levels of CA125 and protein induced by vitamin K absence or antagonist II (PIVKA II). A 63-year-old man was diagnosed with gallbladder cancer with metastases to the liver, based on ultrasonography and computed tomography of the abdomen showing multiple tumorous lesions in the liver and a thickened gallbladder wall. Laboratory data showed high levels of tumor markers: 4647.4 ng/ml AFP, 9987.1 ng/ml CEA, 11704.0 U/ml CA19-9, 847.6 U/ml CA125, and 0.2 AU/ml PIVKA II. AFP in the present case showed an increase in Concanavalin A-nonbinding fraction and an increase inLens culinaris lectin-binding fraction by affinity column chromatography. The patient died of hepatic failure. Autopsy revealed gallbladder cancer consisting of papillary adenocarcinoma and moderately differentiated tubular adenocarcinoma. By immunohistochemical staining, AFP was detected in the papillary adenocarcinoma portion of the primary focus and metastatic tumor cells in the liver, but was not detected in noncancerous liver tissue. CEA and CA19-9 were detected mainly in the tubular adenocarcinoma portion.     

Spontaneous regression of diffuse intrahepatic recurrence with portal vein tumor thrombus after resection of hepatocellular carcinoma

We report a rare case of spontaneous regression of diffuse intrahepatic recurrence with portal vein tumor thrombus (PVTT) after resection of hepatocellular carcinoma (HCC). A 68-year-old man with hepatitis C virus-related liver cirrhosis presented with a 40 mm tumor in the right anterior segment of the liver. The tumor was diagnosed as HCC by typical imaging findings and elevated serum alpha-fetoprotein (AFP) (716 ng/ml) and protein induced by vitamin K absence II (PIVKA II) (8,100 ng/ml). A right anterior sectionectomy of the liver was performed. Microscopically, the tumor was moderately differentiated HCC. Four months after resection, a computed tomography (CT) scan showed diffuse intrahepatic recurrence with PVTT. Serum AFP was 12,319 ng/ml and PIVKA II was 168,000 ng/ml. The patient did not receive any further treatment for HCC including herbal medicine, and stopped smoking. Two years and 5 months later, no lesion was detected on a CT scan when serum AFP was 1.9 ng/ml. Ischemia due to main portal vein occlusion and rapid tumor growth might have induced tumor regression in the present case. Moreover, abstention from smoking might have improved his immunological function.     

Serum CYFRA 21-1 level reflects hepatocellular carcinoma metastasis: study in nude mice model and clinical patients

Our previous proteomics study on human hepatocellular carcinoma (HCC) cell strains revealed that cytokeratin 19 (CK19) was expressed in cells with high metastasis potential; we further studied serum CK19 fragment CYFRA 21-1 level in HCC patients and nude mice model of HCC metastasis. HCC cell line HCCLM3 was injected subcutaneously into 30 nude mice which were then randomized into 6 groups of 5 mice each. The murine serum CYFRA 21-1 and pulmonary metastases were determined 2, 3, 4, 5, 6, and 7 weeks after injection. Serum CYFRA 21-1 levels of 101 normal controls and 108 HCC patients were also determined. In nude mice model, CYFRA 21-1 level increased significantly when pulmonary metastases occurred. Among 108 HCC patients, 24 (22.2%) had increased serum CYFRA 21-1 level. The presence of portal vein tumor emboli was significantly higher in CYFRA 21-1 increased cases (33.3%, 6/24) than in CYFRA 21-1 normal cases (6.0%, 5/84) (x ² = 7.403, P < 0.01). In addition, the percentage of TNM stage III/IV tumor was significantly higher in CYFRA 21-1 increased patients (54.2%, 13/24) than in CYFRA 21-1 normal cases (21.4%, 18/84) (x ² = 9.776, P < 0.005). These results suggest that CK19 may play an important role in HCC metastasis.     

Elevated plasma osteopontin levels in patients with hepatocellular carcinoma

OBJECTIVES: Osteopontin (OPN) is a secreted glycoprotein, frequently associated with various tumors. We investigated the usefulness of plasma OPN level as a biomarker for hepatocellular carcinoma (HCC). METHODS: We determined plasma levels of OPN, alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence II (PIVKA II) in a group of 62 HCC patients, in 60 patients with chronic liver diseases, and in 60 healthy control individuals using a standardized ELISA kit. To determine the source of elevated plasma level of OPN, immunohistochemical analysis of 285 HCC samples on tissue microarray was performed. RESULTS: Plasma OPN levels in the HCC patients (median 954 ng/mL, range 168-5,742) were significantly higher (p-value < 0.001) than those patients with chronic liver diseases (381 ng/mL, 29-1,688) or of a healthy control group (155 ng/mL, 10-766). Within the HCC patient group, plasma OPN level increased significantly with advancing degree of Child-Pugh class and of tumor stage. Diagnostic sensitivity and specificity of OPN for HCC was 87% and 82%, respectively (cut-off value: 617.6 ng/mL). OPN had a greater area under curve value (0.898) than AFP (0.745) or PIVKA II (0.578), suggesting superior diagnostic accuracy of OPN. Immunohistochemistry of 285 samples of HCC showed that OPN was expressed in 92 of 285 tumors (32.3%). OPN expression was found in the malignant hepatocytes and cancer-infiltrating macrophages, not in the noncancerous hepatocytes or Kupffer cells. CONCLUSIONS: These data propose elevated plasma OPN levels as a potential biomarker for HCC.     

Tumor markers in pleural effusion of patients with lung cancer and patients with tuberculous pleurisy]

Carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), NCC-ST-439, carbohydrate antigen 19-9 (CA 19-9), cytokeratin 19 fragment (CYFRA 21-1), sialyl Lewis X-i antigen (SLX), progastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCC) and neuron specific enolase (NSE) were evaluated in the pleural effusion of 39 patients with lung cancer (29 adenocarcinomas, seven small-cell carcinomas, three squamous cell carcinomas) and 43 patients with tuberculous pleurisy. The levels of the tumor markers other than SCC and NSE were significantly higher in lung cancer than in tuberculosis. High levels of CYFRA 21-1 and SCC were observed in squamous cell carcinoma and high levels of ProGRP and NSE were observed in small-cell carcinoma. According to the validity score, sensitivity (%) + specificity (%) - 100, the optimal cut-off levels of pleural effusion were 8.1 ng/ml for CEA, 660 U/ml for CA 125, 2.6 U/ml for NCC-ST-439, 10 U/ml for CA 19-9, 65 ng/ml for CYFRA 21-1, 140 U/ml for SLX, 23.2 pg/ml for ProGRP, 0.6 ng/ml for SCC and 5 ng/ml for NSE. By comparison of validity scores for each optimal cut-off level and of receiver operating characteristic (ROC) curves, we suggest that a CEA assay is the most useful for pleural effusion. The combined assay of CEA + ProGRP and CEA + ProGRP + CYFRA 21-1 were considered to be useful.     

Hepatocellular carcinoma effectively treated by intravenous infusion of cisplatin

We report a rare case of hepatocellular carcinoma (HCC) for which intravenous administration of cisplatin (CDDP) was effective. A 48‐year‐old woman with recurrent HCC was admitted to our hospital. She had undergone right hepatectomy 1 year previously. A large tumor in the liver and multiple lung metastases were found by computed tomography in June 1995. She was icteric, and titers of serum α‐fetoprotein (AFP; 214 ng/ml) and protein induced vitamin K absence or antagonist‐II (PIVKA‐II; 80 AU/ml) were high. According to these findings, she was diagnosed as having nonresectable recurrent HCC with extrahepatic lesions. She was treated by intravenous administration of CDDP. The dose of CDDP was 50 mg and it was infused once a week. One kur of CDDP was 4 weeks, and a total of four kur were administered. We noted that the lung metastases and primary liver tumor resolved after 1 kur of chemotherapy. The levels of serum AFP and PIVKA‐II decreased markedly, to 26 ng/ml and <0.07 AU/ml, respectively. A complete response was obtained, and she maintained a good state of health for the next 6 months, until brain metastases occurred. She died 13 months after the initiation of treatment with CDDP. In general, intravenous CDDP cannot be recommended as a single agent for HCC therapy, but CDDP showed good antineoplastic activity in our patient.     

The Value of Serum α-Fetoprotein in Predicting Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma

Background Many patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT) subsequently develop tumor recurrence; this is the main factor affecting long-term survival after LT. Factors associated with tumor recurrence should be determined to improve the outcome of LT. The purpose of the study was to evaluate the value of α-fetoprotein (AFP) in forecasting tumor recurrence after LT for patients with HCC. Methods AFP data before and after LT for 97 patients with HCC who underwent LT in our center were analyzed retrospectively. Results The mean follow-up time was 17.1 ± 2.1 months for all 97 patients, overall tumor recurrence rate was 32.9% (32/97), and mean recurrence time was 7.2 ± 3.2 months. The most common tumor recurrence sites were liver, lung, skeleton, and other sites. Pre-transplant AFP levels >400 ng/ml were associated with higher tumor recurrence. Post-transplant AFP levels not decreasing to ≤20 ng/ml within 2 months were also indicative of higher risk of recurrence. Conclusions Pre-transplant AFP and the dynamic change of AFP after LT were valuable in predicting tumor recurrence after LT for patients with HCC.     

A Decrease in AFP Level Related to Administration of Interferon in Patients with Chronic Hepatitis C and a High Level of AFP

It is known that there is a very high incidence of hepatocellular carcinoma (HCC) among patients with type C chronic hepatitis and cirrhosis, and α -fetoprotein (AFP) has been widely used as a diagnostic marker for HCC. However, there are some patients showing continuous high AFP values but no evidence of HCC, and some studies have defined such patients as a high-risk group for HCC. In vitro study has shown that interferon (IFN) inhibits cell proliferation and enhances apoptosis as well as specific cytotoxic T lymphocytes against HCC, resulting in direct anticancer actions. In this study, we investigated the effect of IFN on AFP changes in chronic hepatitis C patients. Of 40 patients with chronic hepatitis C in whom diagnostic imaging confirmed the absence of HCC, 24 patients showed high pretreatment AFP values (high AFP group: AFP level > 10 ng/dl; mean ± SD, 46.3 ± 41.5 ng/dl) and 16 showed low pretreatment AFP values (low AFP group: pretreatment AFP level ≤ 10 ng/dl; mean ± SD, 5.3 ± 2.2 ng/dl). Pretreatment clinical parameters were statistically evaluated in relation to the AFP value. In the high AFP group, the platelet count, albumin level, and prothrombin (%) were significantly lower (P = 0.047, P = 0.0002, and P = 0.044, respectively), suggesting that AFP value increases with advancing liver disease. Subsequently 27 patients were administered IFN (IFN group), and the remaining 13 patients were administered Stronger Neo-minophagen C (SNMC), a glycyrrhizin preparation (SNMC group), as a control group receiving liver-protective therapy. Alanine aminotransferase was reduced in both the IFN and the SNMC group (mean, 132.56 to 60.07 mg/ml [P < 0001] and 147.85 to 56.23 mg/ml [P = 0.0240], respectively). AFP was significantly reduced in the IFN group (mean, 30.03 to 12.65 ng/ml; P = 0.0034), but there was no significant change in AFP in the SNMC group (mean, 29.70 to 39.17 ng/ml). AFP is useful for diagnosing HCC; however, some patients show a persistently high AFP level in the absence of HCC, and these patients have been described as a high-risk group for HCC. In this study, we found that IFN therapy but not SNMC universally reduced the AFP baseline. Since AFP is a significant predictor for HCC, therapeutic strategies for hepatitis C, e.g., long-term low-dose IFN treatment, may reduce hepatocarcinogenesis.     

Serum ferritin in hepatocellular carcinoma

The serum ferritin level was detected by radioimmunoassay in 142 patients with hepatocellular carcinoma (HCC). Serum ferritin level was raised (greater than ng/ml) in 38% (54/142) of patients with HCC. There was no difference in serum ferritin levels between stages 1, 2 and 3 HCC. None of the 4 patients with stage 1 HCC had serum ferritin levels above 300 ng/ml. In this small group of patients, measurement of serum ferritin was not a satisfactory indicator of stage 1 HCC. A combination of serum ferritin alpha fetoprotein (AFP) measurements may be useful for a rising suspicion of HCC. We found that a correct diagnosis of HCC was made in 38% (54/142) of patients by measurement of ferritin alone, and in 83.8% (119/142) by measurement of AFP alone, but in 92.3% (131/142) by measurement of a combination of these two markers. Serum ferritin estimation may be helpful in detection of HCC without elevated AFP. Among 12 cases of HCC with serum AFP less than 500 ng/ml, 6 cases (50%) had serum ferritin levels greater than ng/ml. There was no correlation between serum ferritin and AFP, nor between serum ferritin and HBsAg. However, among 12 patients with very high ferritin levels (range 992-3000 ng/ml), 11 (91.7%) had AFP levels of more than 500 ng/ml (mean = 4800 ng/ml, range 500-32000 ng/ml).     

<Emphasis Type="Italic">Lens culinaris</Emphasis> agglutinin-reactive α-fetoprotein and protein induced by vitamin K absence II are potential indicators of a poor prognosis: a histopathological study of surgically resected hepatocellular carcinoma

Background We histopathologically examined Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) and protein induced by vitamin K absence (PIVKA) II-positive HCC to clarify the efficacy of these markers for predicting a poor prognosis. Methods Serum AFP-L3 and PIVKA II was measured in 110 HCC patients. AFP-L3 was measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and PIVKA II by using a high-sensitivity kit. The growth type, capsule formation, capsule infiltration, portal vein invasion, intrahepatic metastasis and histological tumor grade were evaluated pathologically. Results Thirty-eight (35%) HCC patients were AFP-L3-positive, and 63 (57%) were PIVKA II-positive. In AFP-L3-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 66% : 42%, P = 0.027) and a poorly differentiated type (positive : negative = 32% : 6%, P < 0.001) were significantly higher than in AFP-L3-negative HCC. In PIVKA II-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 62% : 28%, P < 0.001), vascular invasion (positive : negative = 63% : 26%, P < 0.001), and intrahepatic metastasis (positive : negative = 38% : 4%, P < 0.001) were significantly higher than in PIVKA II-negative HCC. In both AFP-L3- and PIVKA II-positive HCC, the frequency of a poorly differentiated growth type was significantly higher than in HCC positive for either AFP-L3 or PIVKA II or HCC negative for both AFP-L3 and PIVKA II (both positive : either positive : both negative = 37% : 12% : 0%; P = 0.014, P < 0.001, respectively). Conclusions AFP-L3 was related to progression from moderately differentiated to poorly differentiated HCC, whereas PIVKA II was more specific to vascular invasion. PIVKA II is therefore likely to be a useful indicator of vascular invasion.     

The effectiveness of serum alpha-fetoprotein level in anti-HCV positive patients for screening hepatocellular carcinoma

BACKGROUND/AIMS: In Taiwan, most cases of hepatocellular carcinoma (HCC) are hepatitis B virus (HBV) or hepatitis C virus (HCV) related. The serum alpha-fetoprotein (AFP) level is an important factor in the diagnosis of HCC. There have been many studies discussing the role of AFP in diagnosing HBV-related HCC, but only few concerning HCV-related HCC. In this study, we aimed at analyzing the distribution of AFP levels in anti-HCV positive patients with and without HCC and evaluating the effectiveness of serum AFP levels in screening HCV-related HCC. METHODOLOGY: From 1993-1996, we collected the AFP data of 205 HCC patients retrospectively, who were anti-HCV positive. For comparison, 131 randomized anti-HCV positive patients without evidence of HCC served as the control group. We analyzed the AFP distribution in both groups over the following ranges: < or = 5 ng/ml, > 5-20 ng/ml, > 20-50 ng/ml, > 50-100 ng/ml, > 100-200 ng/ml and > 200-400 ng/ml, and > 400 ng/ml. RESULTS: The distributions of AFP levels in anti-HCV positive patients with HCC were 13.2%, 21.5%, 11.2%, 4.9%, 4.4%, 7.3%, and 37.6%. The distributions in anti-HCV positive patients without evidence of HCC were 34.3%, 55.0%, 8.4%, 1.5%, 0.8%, 0%, 0%. CONCLUSIONS: We found the differences in AFP to be statistically significant between anti-HCV positive patients with and without HCC. A serum AFP level of more than 200 ng/ml highly indicates HCC. However, there is a large overlap between these 2 groups. Thus, in anti-HCV positive patients, AFP level is not a good single reference for diagnosis of HCC. Anti-HCV positive patients should be routinely screened for HCC by image studies along with serum AFP level.     

Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. South Tohoku District Study Group

OBJECTIVE: We evaluated the measurements of serum alpha-fetoprotein (AFP) and the protein induced by vitamin K absence (PIVKA-II) in 734 patients with chronic hepatitis (CH) and liver cirrhosis (LC) who had been followed-up for the development of hepatocellular carcinoma (HCC). METHODS: Serum AFP and PIVKA-II were measured every month and abdominal ultrasonography was performed every 3 months. Youden's index (sensitivity + specificity -1) was calculated. RESULTS: On an average follow-up period of 374.5 days, HCC was detected in three HBsAg-positive LC patients (10.0%/yr), four anti-HCV-positive CH patients (1.35%/yr), 21 anti-HCV-positive LC patients (7.8%/yr), and one patient with both HBsAg- and anti-HCV-positive LC (22.7%/yr). At the time of HCC detection, the size of HCC was 4.7+/-0.6 (mean +/- SD) cm in HBsAg-positive patients and 2.4+/-1.3 cm in anti-HCV-positive patents. Cut-off values of 20 ng/ml for AFP (Youden's index = 0.422) and 60 mAU/ml for PIVKA-II (Youden's index = 0.316) gave the highest index for each marker. When these two markers were combined, cut-off values of 40 ng/ml for AFP and 80 mAU/ml for PIVKA-II gave the highest index (Youden's index = 0.500, sensitivity = 65.5%, specificity = 85.5%, positive predictable value = 14.8%, negative predictable value = 98.3%). The levels of AFP or PIVKA-II increased within three months before the detection of HCC. CONCLUSIONS: Simultaneous measurements of serum AFP and PIVKA-II levels that are performed every 3 months are useful for detecting a developing HCC. The optimal cut-off values for AFP and PIVKA-II may be 40 ng/ml and 80 mAU/ml, respectively.     

增强磁共振成像联合血清甲胎蛋白和脱-γ-羧基凝血酶原诊断肝细胞癌临床价值探讨

目的 探讨钆塞酸二钠（Gd-EOB-DTPA）增强磁共振成像(MRI)联合血清甲胎蛋白（AFP）和脱-γ-羧基凝血酶原（PIVKA-Ⅱ）诊断肝细胞癌（HCC)的临床价值。方法 2015年12月~2017年9月收治的82例肝病患者,经组织病理学诊断HCC组56例,非HCC组26例。罗氏cobas e 601型全自动电化学发光免疫分析系统检测血清AFP,采用LUMIPULSE G1200全自动免疫分析仪酶化学发光法检测血清PIVKA-Ⅱ。全部患者接受MRI检查。采用受试者工作特征曲线（ROC）下面积（AUC）判断各检查诊断的灵敏度、特异度和正确率。结果 HCC患者血清AFP和PIVKA-Ⅱ水平分别为34.5（4.5,594.9） ng/ml和63.5（25.0,2082.0） Mau/ml,显著高于非HCC组【分别为3.4（2.2,11.6） ng/ml和23.0（18.8,28.0） Mau/ml,P<0.01】;血清AFP、PIVKA-Ⅱ和Gd-EOB-DTPA增强MRI检查单独诊断HCC的ROC曲线下面积分别为0.763、0.815和0.907;在单项诊断 HCC 时,血清 AFP和PIVKA-Ⅱ的最佳临床诊断截断点分别为14.4ng/ml和40.5 Mau/ml,其诊断 HCC 的灵敏度、特异度和准确率分别为64.3%、84.6%、67.4%和62.5%、100.0%、74.4%,Gd-EOB-DTPA增强MRI单独诊断HCC的灵敏度、特异度和准确率分别为92.9%、88.5%、91.5%,以Gd-EOB-DTPA增强MRI诊断的效能最高;采用联合试验Ⅰ诊断HCC,其灵敏度为98.2%,特异度为61.5%,准确率为86.6%,采用联合试验Ⅱ诊断HCC的灵敏度为50.0%,特异度为100.0%,准确率为50.0%。联合试验提高了诊断的特异度,但降低了灵敏度。结论 应用血清AFP和PIVKA-Ⅱ检测联合Gd-EOB-DTPA增强MRI检查可提高诊断HCC的效能,综合应用三者联合诊断可以提高诊断HCC的正确性。     

Clinical Utility of Plasma Glypican-3 and Osteopontin as Biomarkers of Hepatocellular Carcinoma

Background/Aims

α-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are reportedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC.

Methods

We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis.

Results

The GPC3 levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors.

Conclusions

The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors.     

Hepatitis B virus,alpha-fetoprotein synthesis,and hepatocellular carcinoma in Zaire

ABSTRACT— We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966–1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%o) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 ± 17.5 years) and females (37.40 ± 15.16 years) was significantly different (p<0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96%) vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumorous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (>20 ng/ml) in 90%) of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19 322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102 565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95%) CI: [182.8, 19952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.     

Plasma levels of human chorionic somatomammotrophin, progesterone, unconjugated oestradiol and oestriol, and alpha-foetoprotein in patients with hydatidiform moles.

Human chorionic somatomammotrophin (HCS), progesterone, and unconjugated oestradiol and oestriol were measured in the plasma of 13 patients with intact hydatidiform moles from week 9 to 19 of pregnancy and in 89 normal women from week 5 to 20 of pregnancy. Plasma alpha-foetoprotein (AFP) was also measured in 9 out of 13 patients and in 23 of the normal women from week 13 to 20 of pregnancy. All the compounds were measured by radioimmunoassay. The plasma HCS concentration in 35 samples from 13 patients with hydatidiform moles ranged from 10 to 910 ng/ml; this was lower than that in normal pregnancy of corresponding duration in eight patients; within the normal range in four patients and high in one patient. The plasma progesterone concentration ranged from 17-5 to 79-2 ng/ml; it was higher than that in normal pregnancy in eight patients and within the normal range in five patients. The plasma unconjugated oestradiol concentration ranged from 1-82 to 8-10 ng/ml; it was higher than normal in six patients and within the normal range in seven patients. The plasma unconjugated oestriol concentration ranged from 0-168 to 1-37 ng/ml, the levels at 15-19 weeks of gestation being significantly lower than those in normal pregnancy at this time (P less than 0-005). Plasma AFP was not detectable in the nine patients (less than 10 ng/ml) whereas it ranged from 10 to 80 ng/ml in 18 out of 23 women in week 13-20 of normal pregnancy. The present results suggest that both plasma oestriol and AFP could be helpful in the diagnosis of hydatidiform mole at about 12-14 weeks though diagnosis could not be made with absolute certainty.     

Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C

Objective: The clinical and morphological significance of a raised alpha-fetoprotein (AFP) level in patients with chronic hepatitis C is undefined. We sought to determine the relation between serum AFP level and liver histology in this population.
Methods: We reviewed the clinical and histological records of 200 consecutively evaluated patients with chronic hepatitis C whose serum AFP levels were recorded. Two groups were studied: group I = 125/200 (62%) patients with normal AFP, < 10 ng/ml; and group II = 75/200 (38%) patients with raised AFP, > 10 ng/ml. The groups were compared according to age, gender, duration of disease, histology, and history of alcohol abuse.
Results: There was no significant difference in serum AFP based on age, gender, alcohol consumption, or disease duration. Significant histological differences were observed: cirrhosis was present in 57 (45%) patients in group I versus 51 (68%) in group II (   p < 0.001  ). Hepatocellular carcinoma was more frequent in group II (14/75 [19%]) than in group I (1/125 [1%]) (   p < 0.001  ). Ten of 77 (13%) noncirrhotic patients and 51/108 (47%) cirrhotic patients had a raised AFP (   p < 0.002  ; relative risk, 3.262; confidence interval [C.I.], 1.912–5.564). A derived AFP level of 17.8 ng/ml maximized specificity for predicting histological outcome: one of 76 (1.3%), 29/108 (26.8%), and 14/15 (93.3%) patients were noncirrhotic, cirrhotic, or had HCC, respectively. This derived AFP value is 35% sensitive and 98.6% specific for cirrhosis, with a positive predictive value of 97.7%.
Conclusions: A serum AFP level >17.8 ng/ml strongly suggests the diagnosis of cirrhosis in a population of patients with chronic hepatitis C.     

Serum Alpha-Fetoprotein Levels During and After Interferon Therapy and the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C

The association between serum alpha-fetoprotein (AFP) levels during and after interferon (IFN) therapy and the development of hepatocellular carcinoma (HCC) was evaluated in patients with chronic hepatitis C (CHC). A total of 263 patients treated by IFN with or without ribavirin were enrolled in the study. Serum AFP levels during and after IFN therapy were investigated retrospectively, and statistical analysis was performed to identify the factors associated with HCC development. During IFN therapy, serum AFP levels significantly decreased, regardless of virologic response to treatment. Increased serum AFP levels (≥10 ng/ml) at the end of IFN therapy (EOT) was a close-to-significant variable affecting the development of HCC (P = 0.057), and a significantly higher cumulative incidence of HCC was seen in patients with increased serum AFP levels at EOT (P = 0.021). Serum AFP level at EOT is a possible predictor of HCC in CHC patients after IFN therapy.     

CYFRA 21-1 and ProGRP, tumor markers of lung cancer, are elevated in chronic renal failure patients

Abstract Serum levels of CYFRA 21-1(cytokeratin-19 fragment) and ProGRP (pro-gastrin-releasing peptide), the new prognostic markers of lung cancer, were measured by ELISA (enzyme-linked immunoadsorbent assay) in 27 (for CYFRA 21-1; male 13, female 14; age 54 ± 17 years) or 22 (for ProGRP; male 9, female 13; age 59 ± 18 years) patients with various serum creatinine levels, 42 haemodialysis (HD) patients (male 24, female 18; age 59 ± 14 years) and 30 continuous ambulatory peritoneal dialysis (CAPD) patients (male 18, female 12; age 48 ± 9 years). All the patients were without clinical and radiological signs of lung cancer. Positive correlations were found between serum creatinine and serum CYFRA 21-1 and ProGRP levels. Serum levels of CYFRA 21-1 were above the cutoff limit (3.5 ng/mL) in 57% of HD patients (mean 4.07 ± 1.56 ng/mL) and in 73% of CAPD patients (mean 4.87 ± 1.56 ng/mL). Serum levels of ProGRP were above the cutoff limit (46.0 pg/mL) in 90% of HD patients (mean 107.0 ± 59.4 pg/mL) and in 93% of CAPD patients (mean 112.4 ± 4.5 pg/mL). Our data indicate that evaluation of renal function is essential when the measurement of these tumor markers is to be applied as one of the diagnostic tools of lung cancer.     

Measurement of serum circulating intercellular adhesion molecule-1 and its clinical significance in hepatocellular carcinoma: preliminary report

Serum circulating intercellular adhesion molecule-1 (cICAM-1) was measured in 50 patients with hepatocellular carcinoma (HCC). The mean cICAM-1 level in the 50 patients was 2220 ng/ml and 43 patients (86%) had a high level of cICAM-1 — more than 1000 ng/ml. Comparative analysis of cICAM-1 and alpha-fetoprotein (AFP) levels in the HCC patients showed that serum AFP level was negative (<20 ng/ml) in five patients or “questionable positive” (20—90 ng/ml) in ten patients, while the levels of cICAM-1 in these patients were 1810 and 1710 ng/ml, respectively. Seven patients who underwent hepatectomy had tumor recurrences during a follow-up period of 6—18 months. Their serum AFP levels were lower than 200 ng/ml (mean value, 27 ng/ml), but their mean cICAM-1 level was 1956 ng/ml at the time tumor recurrence was diagnosed. We suggest that the measurement of serum cICAM-1 is not only useful for prediction of the progression and prognosis of HCC, but that it may also be an important marker for the early diagnosis of the disease, and for monitoring postoperative recurrence, particularly in patients with low levels of serum AFP.