Genetic polymorphism of uridine-diphosphoglucuronosyl transferase 1A7 gene in chronic viral hepatitis and hepatocellular carcinoma

Hepatocellular Carcinoma [HCC] is the most common cause of primary liver neoplasm and the fourth most frequent type of cancer worldwide causing one million deaths per year. Genetic polymorphisms of UDP-glucuronosyltransferases [UGTs], which detoxifies endogenous and environmental carcinogen, have been reported to be associated with HCC. The present study aimed to elucidate the role of UGT1A7 SNP [622 T-C] in the pathogenesis of Hepatocellular Carcinoma [HCC] and whether this polymorphism is associated with elevated bilirubin level or not. This study was conducted on 22 patients with HCC, 25 patients with chronic viral hepatitis B and/ or C and 16 apparently healthy controls. All subjects underwent laboratory tests for Liver and Kidney functions, serological markers [HBV and HCV] and serum AFP as a tumor marker, Genomic DNA from the blood was analyzed for UGT1A7 polymorphism using PCR-RFLP. The prevalence of HCV infection was higher in HCC group compared to other groups. AFP-level significantly increased in HCC than in viral hepatitis and control [p<0.0005]. A statistically significant increase was found in the frequency of risky genotypes [TC, CC] in HCC group as compared to the protective genotype [TT] [P<0.01]. UGT1A7 T allele and C allele were designated as H [high activity] and L [low activity] alleles, respectively. A statistically significant increase was found in frequency of L allele in HCC group [54%] as compared to control group [25%] p=0.03. On the other hand, the H allele showed statistically significant decrease in HCC group [46%] compared to control group [75%] p=0.03. Increase in total bilirubin level in cases harboring UGT 1A7 Polymorphism compared to wild genotype [p<0.01] was observed demonstrating its role in the pathogenesis of hyperbilirubineamia. The UGT1A7 polymorphism was associated with elevated bilirubin level and may play a role in the pathogenesis of HCC

Metabolic syndrome: a reality in obese children and adolescents

The aim of the present study is to contribute to the understanding of metabolic syndrome [MS] risk factors during childhood by examining the diagnostic patterns of MS in obese children. Thirty one obese children and adolescents with BMI >/= 95th percentile were recruited and investigated as group I, in addition to 22 matched age and sex children and adolescents were served as control [group II]. Anthropometric measurements as well as blood pressure were measured. Plasma cortisol, ACTH and suppression test were assessed in all patients. Fasting plasma glucose, insulin, C peptide and lipids profile in addition to glucose tolerance test were analyzed. The metabolic syndrome in children was classified according to modified version of the National Cholesterol Education Program's Adult Treatment Panel III [NCEP-ATP III]. The degree of insulin resistance was determined with the use of a homeostatic model assessment: insulin resistance. Out of the 31 patients assessed, 25.8% of the patients met the diagnostic criteria of metabolic syndrome. Forty percent of the females and 6.25% of the males had 3 or more risk factors. No one of the non-obese control subject met the criteria for the metabolic syndrome. Metabolic syndrome is already a reality for many obese children. Furthermore, there is an urgent need for a clinically useful consensus definition of pediatric metabolic syndrome and national guidelines for proper screening, evaluation and treatment of children at risk for metabolic syndrome

Seminal plasma anti-Müllerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction (TESE) / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To assess seminal plasma anti-Müllerian hormone (AMH) level relationships in fertile and infertile males.</p><p><b>METHODS</b>Eighty-four male cases were studied and divided into four groups: fertile normozoospermia (n = 16), oligoasthenoteratozoospermia (n = 15), obstructive azoospermia (OA) (n = 13) and non-obstructive azoospermia (NOA) (n = 40). Conventional semen analysis was done for all cases. Testicular biopsy was done with histopathology and fresh tissue examination for testicular sperm extraction (TESE) in NOA cases. NOA group was subdivided according to TESE results into unsuccessful TESE (n = 19) and successful TESE (n = 21). Seminal plasma AMH was estimated by enzyme linked immunosorbent assay (ELISA) and serum follicular stimulating hormone (FSH) was estimated in NOA cases only by radioimmunoassay (RIA).</p><p><b>RESULTS</b>Mean seminal AMH was significantly higher in fertile group than in oligoasthenoteratozoospermia with significance (41.5 +/- 10.9 pmol/L vs. 30.5 +/- 10.3 pmol/L, P < 0.05). Seminal AMH was not detected in any OA patients. Seminal AMH was correlated positively with testicular volume (r = 0.329, P = 0.005), sperm count (r = 0.483, P = 0.007), sperm motility percent (r = 0.419, P = 0.021) and negatively with sperm abnormal forms percent (r = -0.413, P = 0.023). Nonsignificant correlation was evident with age (r = -0.155, P = 0.414) and plasma FSH (r = -0.014, P = 0.943). In NOA cases, seminal AMH was detectable in 23/40 cases, 14 of them were successful TESE (57.5%) and was undetectable in 17/40 cases, 10 of them were unsuccessful TESE (58.2%).</p><p><b>CONCLUSION</b>Seminal plasma AMH is an absolute testicular marker being absent in all OA cases. However, seminal AMH has a poor predictability for successful testicular sperm retrieval in NOA cases.</p>

Evaluation of some biochemical markers of cancer prostate

The incidence of Cancer Prostate [PCa] has increased dramatically during the last 10-15 years many strategies have been proposed to enhance the ability of PSA in differentiation of PCa from BPH and f/t PSA was one of those strategies that were reported to improve the diagnostic accuracy of PSA. Of these markers we evaluated prostatic specific antigen [PSA], Neurone specific enolase [NSE], Tissue polypeptide specific antigen [TPS] and Scatter factor [SF], also known as hepatocyte growth factor [HGF]. The present study aimed at evaluating the measurement of serum levels of NSE, TPS and HGF in combination with PSA and I7t PSA in cancer prostate patients to assess their diagnostic and prognostic value in such patients. The study was conducted on 72 patients complaining of obstructive symptoms as frequency and urgency. The first group comprised 26 subjects diagnosed as BPH, the second group consisted of 21 subjects diagnosed as localized PCa and the third group consisted of 25 subjects diagnosed as metastatic PCa. The latter group was further divided according to Gleason score into moderately differentiated [n=13] and poorly differentiated adenocarcinoma [n=12]. All patients were subjected to transrectal ultrasonography [TRUS] and core needle biopsy from the prostate for histopathological examination, and assay of serum tPSA, fPSA measured by chemiluminescent immunometric assay, NSE using electrochemiluminescence immunometric assay, TPS [1RMA] and HGF [ELISA]. Median values of tPSA was significantly higher in metastatic PCa [group III] compared to localized PCa [group II] and BPH patients [group I] [68, 7.0, 2.0ng/ml respectively P<0.001], f/t PSA was significantly lower in PCa patients [group II, group III] compared to BPH patients [0.13, 0.14,0.2 respectively, P=0.004], TPS was significantly higher in metastatic PCa [140U/L] compared to group I and group II [77,65U/L, respectively P=0.004] and HGF was significantly highest in metastatic PCa patients compared to group I and group II [2270, 2132, 1789pg/ml, respectively, P=0.047]. A statistical significant positive correlation was found in the malignant group between PSA and HGF and between [TPS] on one hand and [NSE and HGF] on the other hand. Simultaneous assay of PSA and HGF yielded a sensitivity of 96% in discriminating between BPH from malignant prostate compared to 91% for HGF and 93% for PSA alone. Higher NSE levels were found in higher stage and higher grade PCa. On evaluating the metastatic PCa group, it was found that poor PSA progression free survival [shorter time to androgen responsiveness] is associated with high NSE levels, and with poorly differentiated adenocarcinoma [high Gleason score 8-10]. The value of tPSA in diagnosing cancer prostate is still of uncertainty, however, it is better to be combined with f/tPSA assay. The f/tPSA is useful in discriminating between BPH and PCa especially in the early stage [localized PCa] and thus allowing early intervention and treatment. A cutoff value of 0.24 for f/tPSA is recommended as it detects 87% of cancer cases and at the same time avoids 39% of unnecessary prostate biopsy. Moreover, combining PSA and HGF was more accurate in discriminating between BPH and malignant prostate than either marker alone. HGF alone is of prognostic significance especially in the presence of metastates and correlates well with the stage and grade of cancer prostate. An increase in TPS signifies clinical progression even if PSA is found to remain normal. Thus it is of value in overcoming the relative insensitivity of PSA in some of hormonally treated patients. High NSE levels are of prognostic significance in patients with metastatic PCa treated with androgen withdrawal therapy

Evaluation of some tumor markers in diagnosis and prognosis of hepatocellular carcinoma

Early detection of hepatocellular carcinoma [HCC] is critical for successful treatment. However, the differential diagnosis between HCC and benign hepatic lesions is sometimes difficult and new biochemical markers for HCC are required. The aim of the work was to assess the usefulness of serum AFP, PIVKA-II and TGF- beta1 in the diagnosis and prognosis of HCC and to evaluate the role of serum VEGF in the prediction of venous invasion and metastasis in HCC patients. This study was conducted on 50 patients who were divided into 4 groups; Group I: 10 patients with liver cirrhosis, Group II: 20 patients with benign hepatic focal lesion [HFL], Group III: 10 HCC patients without metastasis before and after treatment in the form of per-cutaneous alcohol injection, and Group IV: 10 HCC patients presenting with metastasis. Ten apparently healthy subjects were taken as a control group. Patients as well as the control subjects were submitted to the following: A] Full clinical examination, B] Imaging techniques including abdominal ultrasonography and CT scan. Patients with HCC were subjected to bone scan and MRI brain, chest and abdomen to detect distant metastasis, C] Laboratory investigations including: complete liver function tests, prothrombin time and concentration, serological examination for hydatid disease, cytological examination of fluid aspirated from infectious cyst, serodiagnosis of HCV and HBV infection, serological markers including AFP, PIVKA-II, VEGF and TGF- beta1 Lastly, histopathologic examination of liver biopsies obtained from focal lesions of HCC patients. A statistically significant difference in the median serum level of AFP, PIVKA-II, VEGF and TGF- beta1 was found on comparing the HCC groups [with and without metastasis] with the control, benign focal lesions and cirrhotic groups. The median serum PIVKA-II level was significantly lower in the non-metastatic HCC group [16.2 ng/ml] compared to the metastatic group [33.6 ng/ml] [P=0.001]. On the other hand, the median serum VEGF level was significantly higher in the non-metastatic HCC group [2580 pg/ml] compared to that of the C group with distant metastasis [1840 pg/ml] [P=0.008]. There was a significant lowering of median serum level of all parameters in the non-metastatic HCC patients after ablation therapy. A statistically significant negative correlation was observed between serum VEGF and serum PIVKA-II in the non-metastatic HCC group. Regarding sensitivity and specificity of the four serological markers: at a cut-off level of 28 ng/ml, AFP yielded a sensitivity of 80% and a specificity of 97%, at a cut-off level of 12.5 mAU/ml for PIVKA-II, the sensitivity was 80% and the specificity was 97%, VEGF revealed a sensitivity of 96.7% and a specificity of 85% at a cut-off level of 780 pg/nil, and lastly TGF- beta1 yielded a sensitivity of 76.7% and a specificity of 97% at a cut-off level of 32.4 ng/ml. Combination of these markers improved both sensitivity and specificity, as combination of AFP and PIVKA-II yielded a sensitivity of 93.3% and a specificity of 98.2%, and for AFP with TGF- beta1, the sensitivity was 87.5% and the specificity was 99%. Combined determination of serological markers could be used as a highly valuable tool for screening and diagnosis of HCC. They could also be used as prognostic markers hence decreasing the need for more invasive procedures such as liver biopsy