CHANGES OF SERUM ALPHA FETOPROTEIN BEFORE AND AFTER RADIOIMMUNOTHERAPY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

Thirtytwo patients with surgically verified unresectable table hepatocellular carcinoma (HCC) have been treated by radioimmunotherapy (RIT) using intrahepatic arterial administration of￣(131)I anti HCC monoclonal antibody (Hepama1) combined with hepetic artery ligation. Twenty of them had abnormal serum alpha fetoprotein (AFP,>20 ng/ml). Single photon emission computed tomography (SPECT) scan and quantitative assay of AFP were performed after RIT. The results revealed that when the tumor to liver ratio (T/L) was higher than 3.5 (Group A , n =3) , the serum AFP level declined markedly and then kept in stable for a tongtime; when the T/L ratio was less than 1.2 (Group C ,n=5), the serum AFP level did not change evidently within 2 months postinfusion; while the T/L ratio was between 1. 2 3. 5 (Group B, n= 12) , the serum AFP level increased transiently and then decreased within 2 4 weeks postinfusion. Sequentiat resection was achieved in all of the 3 patients of Group A, in 6 patients (50%) of Group B, and none in Group C. The correlation of serum AFP and effective treatment demonstrates the usefulness of this oncofetal protein marker as an indicator of neoplastic activity for HCC and T/L ratio might be a good indicator to predict tumor response to RIT in patients with

The Combined Diagnostic Accuracy of Serum Alpha Fetoprotein and Des-Gamma Carboxyprothrombin in Hepatocellular Carcinoma among Chronic Liver Disease Patients in Ilorin

Introduction :Chronic liver disease (CLD) is a disease of public health importance. CLD is defined as a clinical syndrome of liver disease lasting for at least six months with histology showing varying degree of hepatocellular necro-inflammation and fibrosis with or without neoplastic transformation. The disease is a spectrum that manifests initially as chronic hepatitis which may progress to liver cirrhosis and ultimately hepatocellular carcinoma (HCC). The current practice in the field of Gastroenterology has shifted from invasive methods of diagnosing HCC to non-invasive methods using tumor biomarkers. Various biomarkers of HCC have been proposed, but the largest body of evidence exists with alpha-fetoprotein (AFP). Most of the studies on the combined diagnostic accuracy of AFP and des-gamma-carboxyprothrombin (DCP) were done in other populations outside Nigeria. It is necessary to determine the combined diagnostic accuracy of the two tumor markers for early detection of HCC in North-central Nigeria. Materials and Methods: This study was a cross-sectional study and ethical clearance was obtained from the ethical and research committee of UITH, Ilorin. A total of 190 participants consisting of 125 cases and 65 healthy controls that were age and sex-matched were studied. Patients with extra-hepatic malignancies were excluded. The serum levels of AFP and DCP were determined using the enzyme-linked immunoassay (ELISA) technique. A detailed questionnaire was used to document the socio-demographic characteristics, clinical features as well as results of laboratory/radiologic parameters. Percutaneous liver biopsy was carried out on patients that were fit. Test of association between categorical variables was carried out using the Chi-Square Test. The sensitivity, specificity, positive and negative predictive values of the two tumor markers were determined by the area under curve (AUC) at various cut-off levels using the receiver operating characteristic (ROC) curve analysis. Statistical significance was set at p value < 0.05. AFP Quantitative test kit (alfabeto-RiakiDainabot Radioisotope laboratory, Japan) and DCP Qualitative test kit (EiTest MONO P-II kit) were used to assay AFP and DCP respectively. Liver biopsy needle (Menghini needle) was used to carry out liver biopsy. Results: Using a cut-off of 400 ng/ml, the sensitivity of serum AFP for diagnosing HCC was 51.3%. The specificity of AFP at the same cut-off was 87.8%. The positive and negative predictive values were 92.8% and 49.3% respectively. Using a cut-off of 7.5 ng/ml, the sensitivity of serum DCP for diagnosing HCC was 57.1%. The specificity of DCP at the same cut-off was 63.4%. The positive and negative predictive values were 76.2% and 41.9% respectively while the accuracy was 59.2%. The diagnostic accuracy of combined serum AFP and DCP for diagnosis of HCC in University of Ilorin Teaching Hospital, Ilorin was 64.9%. The sensitivity of combined serum AFP and DCP for diagnosing HCC was 55.6%. The specificity of combined serum AFP and DCP was 95.6%. The positive and negative predictive values were 96.2% and 52.3% respectively. Conclusion: Combining these two tumour markers does not significantly improve the diagnostic accuracy of HCC and chronic HBV remains a strong aetiological agent of HCC in UITH, Ilorin.

Detection of blood AFPmRNA in nude mice bearing human HCC using nested RT-PCR and its significance

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Detection of hepatoma cells in peripheral blood of HCC patients by nested RT-PCR

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Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review

BACKGROUND Hepatocellular carcinoma(HCC)is a frequent cause of cancer related death globally.Neutrophil to lymphocyte ratio(NLR)and albumin bilirubin(ALBI)grade are emerging prognostic indicators in HCC.AIM To study published literature of NLR and ALBI over the last five years,and to validate NLR and ALBI locally in our centre as indicators of HCC survival.METHODS A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years.The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses.Additionally,we also investigated HCC cases between December 2013 and December 2018 in our centre.RESULTS There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years.Our local cohort of patients showed NLR to have a significant negative relationship to survival(P=0.011).There was also significant inverse relationship between the size of the largest HCC nodule and survival(P=0.009).Median survival with alpha fetoprotein(AFP)<10 KU/L was 20 mo and with AFP>10 KU/L was 5 mo.We found that AFP was inversely related to survival,this relationship was not statically significant(P=0.132).Mean survival for ALBI grade 1 was 37.7 mo,ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5mo.ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.CONCLUSION NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein.ALBI grade performs better than Child Turcotte Pugh score.These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein,these markers could give a better understanding of the patient disease progression.NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.

Combined measurement of serum tumor markers in patients with hepatocellular carcinoma

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Com bined effect of alphafetoprotein antisense oligodeoxynucleotidesand 5-fluorouracil on human hepato ma cell growth

Objective To investigate the effect of alpha fetoprotein (AFP) antisense phosphorothioate oligodeoxynucleotides in combination with 5 fluorouracil (5 FU) on the growth of BEL 7404 human hepatoma cells in vitro Methods Phosphorothioate oligodeoxynucleotides were synthesized by β cyanoethyl phosphoramidite chemistry AFP gene expression in human hepatoma cells was determined by avidin biotin peroxidase complex (ABC) immunocytochemical method Cell growth in the presence or absence of experimental agents was measured using 3 (4, 5 dimethylthiazol 2 yl) 2, 5 dipheny ltetrazolium (MTT) microculture tetrazolium assay Results AFP antisense oligomers markedly suppressed the growth of BEL 7404 human hepatoma cells in vitro by sequence specific blocking of the AFP gene expression in the cells (P<0 05) 5 FU also inhibited the hepatoma cell growth in a dose dependent manner when used alone (P<0 05) The combined treatment with AFP antisense oligomers and 5 FU showed significantly enhanced hepatoma cell growth inhibition than either AFP antisense or 5 FU treated cells alone (P<0 05) Conclusion Combined use of AFP antisense oligomers and 5 FU could more effectively inhibit the growth of BEL 7404 human hepatoma cells in vitro

Maternal seru m screening for Down syndro me in a teaching hospitalin Hong Kong

Objective To study prospectively the use of maternal serum alpha fetoprotein (AFP) and total β human chorionic gonadotropin (hCG) concentrations for screening of Down syndrome in Hong Kong.Methods AFP and total β hCG were measured in serum samples from 1638 singleton Chinese pregnancies at 14-22 weeks of gestation, recruited over a twelve month period. Gestational ages were determined by ultrasonographic parameters measured at the same visit as the test for all cases. The gestational age specific and weight adjusted medians for serum AFP and total β hCG were calculated. Risk for fetal Down syndrome (FDS) was derived by mathematical modeling of the medians together with maternal age. Amniocenteses were offered to women with a calculated FDS risk of 1∶270 or greater.Results The gestational age specific and weight adjusted medians for maternal serum AFP were similar to previous studies while that of total β hCG were higher. A total of 101 patients (6.1%) were classified as being high risk for FDS, including 3.4% (48/1394) of those younger than 35 years of age and 21.7% (53/244) of those who were 35 or above. There were 4 cases of Down syndrome, 1 case of Turner syndrome and 1 of Edward syndrome. Three out of the four cases of Down syndrome were screened positive, corresponding to a detection rate of FDS of 75%. A case of Turner syndrome was also screened positive. A case of trisomy 18 was found to have very low levels of AFP [0.262 multiple of median (MoM)] and total β hCG (0.115 MoM).Conclusions Maternal serum screening using double biochemical markers (AFP and total β hCG) in combination with gestational dating by ultrasonography is effective in the detection of fetal Down syndrome and possibly other chromosomal disorders in Chinese pregnant women.

Hepatoid carcinoma of the pancreas:a case report

In 1970, a gastric adenocarcinoma patient with increased alpha fetoprotein （AFP） in his serum and liver metastatic tumor was reported by Bourreilile et al. At that time, it was realized that a gastric adenocarcinoma could produce AFP. In 1985, Ishikura et al reported a hepatocellular carcinoma （HCC）-like differentiation in a primary gastric tumor and first proposed the conception of a ＂hepatoid carcinoma＂. Subsequent documentation of this unique histopathologic feature has been made in other extrahepatic sites including the esophagus, papilla of Vater, colon, lung, gallbladder, adrenal gland, kidney, urinary bladder, ovary, uterus, vagina, testicle, and small intestine. However, the number of cases is very small. Hepatoid carcinoma is a primary extrahepatic neoplasm exhibiting features of hepatocellular carcinoma in terms of morphology, immunohistochemistry and biological behavior. But histopathologically it is very rare. Many but not all cases, present with an elevated serum AFP. Taking a wide view of various literatures it is evident that hepatoid carcinoma has mostly been found in the stomach and very rarely in the pancreas. To date, only eight cases of hepatoid carcinoma of the pancreas have been reported in the literature. We present a case of hepatoid carcinoma of the pancreas arising in an elderly man without evidence of residual disease eight months after local resection of the tumor.

Testicular germ cell tumors type 2 have high RNA expression of LDHB,the gene for lactate dehydrogenase subunit B

This study analyzed RNA expression of genes for three serum tumor markers,alpha fetoprotein(AFP),human chorionic gonadotropin(hCG),and lactate dehydrogenase(LDH),in patients with testicular germ cell tumors(TGCT)type 2.The gene AFP encodes AFP,the gene for chorionic gonadotropin beta polypeptide 5(CGB5)encodes a major part of the specific beta subunit of hCG,and the genes for LDH subunit A(LDHA),LDH subunit B(LDHB),and LDH subunit C(LDHC)encode three different subunits of LDH.LDHB encodes the LDHB subunit present as a tetramer in LDH isoenzyme 1(LDH-1).We examined three datasets with 203 samples of normal testis tissue(NT)and TGCT type 2.Yolk sac tumor(YST)expressed RNA of AFP fourteen thousand times higher than seminoma(SE),embryonal carcinoma(EC),and teratoma(TER)combined(P=0.00015).In the second microarray,choriocarcinoma(CC)expressed RNA of CGB5 ten times higher than other histologic types of TGCT combined.EC expressed RNA of LDHB twice higher than SE,YST and TER combined(P=0.000041).EC expressed RNA of LDHB higher than that YST expressed RNA of AFP and that CC expressed RNA of CGB5.In conclusion,TGCT type 2 expressed RNA of LDHB markedly higher than the RNA of 23 other candidate genes for TGCT type 2.

Advances in early diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most recurrent hepatic malignancy and the third in the cancer-related casualties in the west.The frequently-documented causes of HCC are chronic liver infections by hepatitis B virus or hepatitis C virus,nonalcoholic fatty liver disease,cirrhosis,exposure to aflatoxins and tobacco smocking,etc.Clinical presentation of this fatal disease ranges from asymptomatic to upper abdominal pain or common health conditions like weight loss or lethargy.Among current surveillance strategy for suspected patients,liver imaging and serum alpha fetoprotein estimation has been regularly recommended.However,sensitivity of this diagnostic methodology especially in early detections,often suffers from compromised sensitivity and selectivity.Various image based and serological biomarkers for HCC has been introduced in recent decades with varied sensitivity as stand-alone or combined diagnostic protocol.The current article will review the status of HCC diagnosis with respect to common diagnostic protocol,and upcoming novel biomarkers.

Evaluation and impact of different biomarkers for early detection of hepatocellular carcinoma

Worldwide,hepatocellular carcinoma(HCC)is a frequent complication of liver diseases and remains a major cause of cancer-related mortality.In addition,the prevalence of nonalcoholic steatohepatitis(NASH)as prerequisite of hepatocarcinogenesis,even in the absence of cirrhosis,is rising rapidly.The early detection of HCC has been crucial in improving the survival outcomes of those patients.However,in the mostly obese NASH population,diagnostic sensitivity of ultrasound-based HCC screening approaches is limited.On the other hand,biomarkers for HCC show promising potential to improve early detection,providing reproducible,investigator-independent results that can be used either alone or integrated with other biomarkers for scoring models.In the past,validation has been limited due to a lack of prospective longitudinal cohort studies.At present,large-scale retrospective phase-III-biomarker-development gives hope for the availability of biomarker-based screening approaches in the near future.This review focuses on the potential impact of biomarkers on surveillance strategies,potentially allowing for earlier HCC diagnosis.