Role of the criteria based on preoperative serological indexes of AFP and GGT in predicting long-term survival of patients with hepatocellular carcinoma after liver transplantation / 器官移植

Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

Prediction of microvascular invasion in hepatocellular carcinoma patients by preoperative neutrophil-lymphocyte ratio and cancer-related factors / 中华肝胆外科杂志

Objective To predict the presence of MVI,the general clinicopathological of HCC patients' data of the preoperative neutrophil-lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR),altplatelet ratio (APRI) were evaluated.Methods 143 cases of HCC patients who underwent radical resection and ≤ 5 cm of tumor diameter in Chifeng Clinical Medical School of Inner Mongolia Medical University from January 2011 to December 2014 were analysed retrospectively and followed up.The relationship between NLR,PLR,APRI and other clinical parameters was evaluated.Results According to ROC Curve,the NLR truncation value was 2.00,PLR to 115.00,APRI 1.6.The single factor analysis of x2 test showed that NLR (x2=6.419;P＜0.05),APRI (x2=3.975;P＜0.05),AFP (x2=33.37;P＜0.05),Degree of differentiation (x2 =9.839;P＜0.05) were significant differences between MVI positive (MVI+) and negative (MVI-) groups,and the difference was statistically significant;Logistic regression multifactor analysis showed that NLR (OR 2.678;95％ CI 1.033～6.944;P＜0.05) and AFP (OR 1.724;95％CI 1.023～2.905;P＜0.05) are independent predictors of MVI.Conclusion Preoperative NLR and AFP are convenient,economical and reliable hematological indices for predicting the presence of MVI in HCC patients.

Differences in clinical features between hepatitis B virus positive and negative patients with primary liver cancer / 中华肝胆外科杂志

Objective To investigate the differences in clinical features between primary liver cancer (PLC) patients with positive and negative hepatitis B virus (HBV) and discuss the correlation of positive HBV and TNM staging.Methods Clinicopathological data of 430 patients with primary liver cancer who underwent partial hepatectomy in Henan Cancer Hospital from November 2012 to December 2015 were retrospectively reviewed.The cases were divided into HBV-positive PLC group (n =362) and HBV-negative PLC group (n =68) in according to the HBV infection status.x2 test was performed to analyze the clinical feature differences of the two groups.Spearman rank correlation was used to assess the differential clinical features and TNM staging of HBV-positive PLC.Results There were statistic differences in gender,age,AFP level,tumor numbers,tumor size,histopathological types and TNM staging between two groups (P ＜0.05).Furthermore,AFP level,tumor numbers,tumor size and histopathological types showed positive correlation with TNM staging (all P ＜ 0.05).Conclusions A number of remarked differences in clinical feature of gender,age,AFP level,tumor numbers,tumor size,histopathological types and TNM staging could be observed in HBV-positive PLC patients compared with HBV-negative patients.HBV-positive PLC patients may have positive correlations of AFP level,tumor numbers,tumor size,histopathological types and TNM staging.

Evaluation of the UniCel(TM) DxI 800 Immunoassay Analyzer in Measuring Five Tumor Markers

PURPOSE: Tumor marker concentrations in a given specimen measured by different analyzers vary according to assay methods, epitopes for antibodies used, and reagent specificities. Although great effort in quality assessment has been instituted, discrepancies among results from different analyzers are still present. We evaluated the assay performance of the UniCel(TM) DxI 800 automated analyzer in measuring the alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA 15-3 and CA 19-9 tumor markers. MATERIALS AND METHODS: The linearity and precision performance of the five tumor marker assays were evaluated, and concentrations of the respective markers as measured by DxI were compared to those measured by other conventional analyzers (ADVIA Centaur(TM) and Vitros(TM) ECi) using 200 specimens collected from 100 healthy persons and 100 patients with respective cancers. RESULTS: The linear fits for all five tumor markers were statistically acceptable (F=4648 for AFP, F=15846 for CEA, F=6445 for CA 125, F=2285 for CA 15-3, F=7459 for CA 19-9; p<0.0001 for all). The imprecision of each tumor marker assay was less than 5% coefficient of variation, except for low and high concentrations of AFP. The results from UniCel(TM) DxI 800 were highly correlated with those from other analyzers. CONCLUSION: Our results demonstrate that UniCel(TM) DxI 800 has good linearity and precision performance for the tumor markers assayed in this study. However, there were discrepancies between assaying methods. Efforts to standardize tumor marker assays should be undertaken, and the redetermination of cut-off levels is necessary when developing methods of analyzing tumor markers.

The Influence of Alpha-fetoprotein on Natural Suppressor Cell Activity and Ehrlich Carcinoma Growth

The influence of alpha-fetoprotein (AFP) on the bone marrow (BM) natural suppressor (NS) cells of intact Ehrlich carcinoma -bearing CBA mice was studied. Bone marrow NS cells were fractionated into three fractions by isopycnic centrifugation on percoll gradients: NS1 (rho=1.080 g/ml), NS2 (rho=1.090 g/ml) and NS3 (1.100>rho>1.090 g/ml). These fractions were highly different in their sensitivity to known NS cell inductors (interleukin (IL)-2, IL-3 or histamine). None of the NS fractions isolated from the intact mice spontaneously produced antiproliferative activity, however, they showed a high level of NS (antiproliferative and natural killer cell inhibitory) activity under the influence of AFP. A single injection of AFP to intact mice led to an increase of spontaneous NS activity and the inhibition of natural killer cell activity. NS activity, especially NS2, was increased in when tumor cells were subcutaneously inoculated three days after AFP injection. In the AFP-treated mice, the tumor mass at 14 days was 60% larger than that in the untreated mice. Our data confirmed that AFP is a tumor marker that can inhibit cancer immunity and plays a role in cancer pathogenesis.

Acute Exacerbation of Hepatitis in Liver Cirrhosis with Very High Levels of alpha-Fetoprotein But No Occurrence of Hepatocellular Carcinoma

Aminotransferase levels do not always increase during acute hepatitis or during an acute flare-up of chronic hepatitis. Persistently increased levels of serum alpha-Fetoprotein in an adult with liver disease suggest not only the presence or progression of hepatocellular carcinoma or its recurrence after hepatic resection or after other therapeutic approaches such as chemotherapy or chemoembolization, but also it suggests that there is an acute exacerbation of hepatitis or liver cirrhosis. We report here on two unusual cases of HBV- and HCV-related liver cirrhosis with acute exacerbation of hepatitis in which there was an insignificant elevation of the aminotransferase levels, but there were markedly increased alpha-Fetoprotein levels observed. The levels of alpha-Fetoprotein decreased gradually in both cases since the beginning of antiviral therapy, which implies that the increased levels were due to aggravation of the accompanying hepatitis. These cases also emphasize that using only the measurement of alpha-Fetoprotein is not sufficient for the diagnosis of hepatocellular carcinoma, and that this diagnosis also requires a more specific measurement such as AFP L3 along with the standard imaging studies.

An Analysis of Cost-Effective Screening Interval for HCC in Korean Hepatitis B Virus Carriers

BACKGROUND: The purpose of this study was to evaluate the cost-effectiveness of screening tests (AFP and US) for early detection of primary hepatocellular carcinoma (HCC) and its optimal screening interval in Korean hepatitis B virus carriers. METHODS: Data relating to tumor incidence, efficacy of screening tests, tumour growth times and various cost for detecting HCC were obtained from reviews of Korean literature. Decision analysis technique was used to calculate the efficacy of these screening tests and screening interval. RESULTS: When the doubling time of HCC was 6 months, the most cost-effective screening interval of each AFP and US was 6 months, respectively. The optimal screening intervals of AFP and US were 3 and 5 months for each, respectively, and 7 months for both when a detection rate of 80% was expected. These results were significantly altered when the different tumour growth times reported in other literatures were applied. CONCLUSION: If the doubling time of HCC was 6 months, the optimal screening interval was 7 months on using both tests. Because the tumour doubling time alters the optimal screening interval, further evaluation on the doubling time of Korean hepatoma is needed.

Study of plasma transforming growth factor-beta 1 level as a useful tumor marker in various cancers

BACKGROUND: Many investigators have found transforming growth factor-1 (TGF-1) to be elevated in tumors. Changes in responsiveness to TGF-1 have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-1. However, a little is known about the association of TGF-1 with progression of malignant tumor. METHODS: In this study, we measured the plasma level of TGF-1 in various cancer patients and evaluated the utility of plasma TGF-1 as a possible tumor marker. Plasma TGF-1 levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-1 in the aspects of sensitivity and specificity. RESULTS: The mean of plasma TGF-1 levels was 1.2 19 +/-0.834 ng/ml in normal controls, 5.491 +/-3.598 ng/ml in breast cancer, 12.670 +/-10.386 ng/ml in lung cancer, 5.747 +/-3.228 ng/ml in hepatocellular carcinoma and 10.854 +/-7.996 ng/ml in cervical cancer. In comparison with CEA and AFP, TGF-1 is more sensitive. CONCLUSION: We conclude that the high levels of TGF-1 are common in the plasma of cancer patients. These result s suggest that the plasma TGF-1 level can be a potent tumor marker in various cancer patients.

Normal Range of Amniotic Fluid Alpha-Fetoprotein in Midtrimester Korean Pregnant Women / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to determine normal amniotic fluid alpha-fetoprotein level in midtrimester Korean pregnant women whose neonatal outcomes were normal. METHODS: Amniotic fluid alpha-fetoprotein(AFAFP) levels were measured by specific radioimmunoassay (RIA) in midtrimester pregnant women for various indications of amniocentesis from May 1992 to July 1999 at Seoul National University Hospital. Normal ranges were obtained from 640 singleton pregnancies in which neonatal outcomes were normal. RESULTS: Median values of AFAFP in Korean pregnant women were 13,250ng/mL, 12,900ng/mL, 11,150ng/mL, 9,430ng/mL, 8,019ng/mL, 6,800ng/mL, 5,850ng/mL, 5,750ng/mL, 5,210ng/mL, 3,420ng/mL at 15 week, 16 week, 17 week, 18 week, 19 week, 20 week, 21 week, 22 week, 23 week, 24 week, respectively. CONCLUSION: This determination of the median values and the normal range of AFAFP level by each gestational week in uncomplicated Korean women could be used reference values for prenatal diagnosis of various disorders like open neural tube defect.

A study on the validity of serum a alpha-fetoprotein for the screening of hepatocelluar carcinoma among Korean adults

BACKGROUND: Serumc alpha-fetoprotein(aFP) is a useful diagnostic test on hepatocellular carcinoma(HCC) However, it is still questionable appropriate screening test or not. METHODS: A total of 24,050 patients who visited the General Health Screening Center of Asan Medical Center from June, 1993 to June, 1994 were reviewed by chart and telephone survey. Among them 70 cases where serum aFP were elevated > 20ng/ml and 16 cases where HCC was suspected by abdominal ultrasonogram were selected and investigated for the existence of HCC. Four groups were divided into HBsAg(+), Anti-HCV(+), increased AST/ALT(abnormal LFT) and normal gruoup. Each group was evaluated for sensitivity, specificity, positive predictive value and negative predictive value of serum aFP for HCC. RESULTS: The prevalence of elevated aFP was 0.29%(70/24,050). There was a statistically significant difference between sexes. And the total number of HCC as 10 cases (42/100,000). With aging, the prevalence of HCC was increased. The prevalence rate of elevated serum aFP and HCC had significant difference in anti-HCV(+), HBsAg(+) and abnormal LFT group compared to normal group (sGOT 40U/l or sGPI > 40U/l), HBsAg(+) and Anti HCV(+) people.

Hepatoid adenocarcinoma of the stomach: report of 3 cases and review of the literature in recent ten years / 中国癌症杂志

Purpose:To analyze the clinical manifestations, so the diagnosis of hepatoid adenocarcinoma of the stomach (HAS) may be made and treatment instituted as early as possible. Methods:A total of 65 cases of HAS reported in the literature in recent ten years reviewed.Results:①Clinical symptoms and signs: The incidence of HAS in male was higher than that in female (6.2:1).Upper abdominal discomfort and physical signs of mass bclow the sternum were most commonly seen.②Diagnosis: The serum content of AFP were discombfort high level with a positive rate of 66.7%(22/33). The positive rate of AFP expression with immunohistochemical method was 94.5%(52/55).The percentage of liver metastasis detected by US B or CT was 20.5%(9/44) preoperation, and mostly seen at the gastric sinus was ahout 63.3%(19/30). The final diagnosis of HAS depends on gastrocopy and pathology. ③Treatment and Prognosis: The possibility of radical operation(D 2 ) is only 17.9%(5/28). The death ratio within one year was 56.3%(18/32).Conclusions: HAS is primarily a gastric carcinoma. The serum AFP levels are help fulin the diagnosis and differential diagnosis of HAS. The diagnostic evidence of HAS is dependant on its specific forms. The prognosis is often poor because of frequent liver metastasis.

A case of recurrent infantile polycystic kidney associated with hydrops fetalis

Nonimmune hydrops fetalis is becoming a predominant form of fetal hydrops due to the declining incidence of immune hydrops fetalis triggered by Rh isoimmunization. Infantile polycystic kidney appeared to be related to hydrops fetalis whether it is causal or merely coincidental and may represent another entry to differential diagnoses. Infantile polycystic kidney was diagnosed by an elevated maternal serum alpha-fetoprotein (AFP) value coupled with an ultrasonographic abnormality scanned as a multicystic mass with ascites in the fetal abdomen antenatally. This study presents a case of infantile polycystic kidney that resulted in a stillborn baby with hydrops fetalis and extensive placental calcification; it was the first case in Korea in which nonimmune hydrops fetalis was associated with infantile polycystic kidney in consecutive siblings by autosomal recessive inheritance in one family. In addition, this paper comprehensively reviews the incidence, etiology, prenatal diagnosis and proper management of nonimmune hydrops fetalis.

Alpha-Fetoprotein Values in Maternal Serum and Amniotic Fluid for Prenatal Screening of Genetic Disorders

Prenatal alpha-fetoprotein screening may serve as an index of suspicion of many congenital anomalies of the fetus including neural tube defect and aneuploid fetus. This study was undertaken to determine the normal ranges of AFP in maternal serum and amniotic fluid at 9 to 41 weeks gestation which thus far had not been established in Korea. Normal ranges of maternal serum and amniotic fluid AFP from 9 to 34 weeks and from 16 to 41 weeks gestation were obtained respectively from 198 uncomplicated pregnant women delivered of normal singleton baby. Maternal serum AFP values showed an increasing trend from 12 weeks gestation reaching a peak level at 29 to 34 weeks gestation and after which there was a gradual decline. Amniotic fluid AFP values was the highest at 17 weeks gestation and declined as pregnancy approached term. The correlation of a median value between AF AFP and MS AFP was 100 to 1 in ratio in each week. The authors conclude that this initial experience in Korea with maternal serum AFP values could efficiently detect genetic disorders, perhaps with high sensitivity and provide a proper management scheme of pregnant women with abnormal high and low AFP values during the midtrimester of pregnancy.