Ankush Mittal

Impact of Various Tumor Markers in Prognosis of Gastric Cancer. A Hospital Based Study from Tertiary Care Hospital of Kathmandu Valley

BACKGROUND To obtain the maximum additional information about the prognosis of gastric cancer, we compared CA-50 with other previously defined markers. MATERIALS AND METHODS This hospital based study was carried out in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between 1st July 2012 and 31st December 2012. The variables collected were age, gender, AFP, CEA, CA19-9, and CA50, assayed with ELISA reader for all cases. The cut off values for serum AFP, CEA, CA19-9, and CA-50 were 10 μg/l, 10 μg/l, 37 U/ml, and 20 U/ml, respectively according to the manufacturers instructions. Approval for the study was obtained from the institutional research ethical committee. RESULTS Of the 40 examined patients, 13 patients had tumors located in the upper third of the stomach, 6 patients had tumors in the middle third, 16 patients had tumors in the lower third, and 5 patients had tumors occupying two-thirds of the stomach or more. The distribution of lymph node staging of the patients was as follows: 7 patients belonged to N0, 9 patients to N1 stage, 10 patients to N2 stage, and 14 patients to N3 stage. The statistical method of Cox proportional hazards using multivariate analysis also illustrated that tumor markers including CEA (2.802), CA19-9 (2.690), CA50 (2.101), were independent prognostic factors, as tumor size (1.603), and lymph node stage (1.614). CONCLUSIONS The tumour markers now available, like CEA, CA 19-9 and CA 50, chiefly perceive advanced gastric cancer. The preoperative rise in those tumour marker level have a prognostic significance and may be clinically helpful in choosing patients for adjuvant management.

Role of Hyperinsulinemia in Increased Risk of Prostate Cancer: A Case Control Study from Kathmandu Valley

AIM To investigate the effect of hyperglycemia and hyperinsulinemia on prostate cancer risk. MATERIALS AND METHODS This hospital based study was carried out using data retrieved from the register maintained in the Department of Biochemistry of a tertiary care hospital of Kathmandu, Nepal between 31st December, 2011 and 31st October, 2013. The variables collected were age, serum cholesterol, serum calcium, PSA, fasting blood glucose, serum insulin. Analysis was performed by descriptive statistics and testing of hypothesis using Excel 2003, R 2.8.0, Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. RESULTS Of the total 125 subjects enrolled in our present study, 25 cases were of PCa and 100 were healthy controls. The mean value of fasting plasma glucose was 95.5 mg/dl in cases of prostatic carcinoma and the mean value of fasting plasma insulin was 5.78 μU/ml (p value: 0.0001*). The fasting insulin levels μU/ml were categorized into the different ranges starting from ≤2.75, >2.75 to ≤4.10, >4.10 to ≤6.10, >6.10μU/ml. The maximum number of cases of prostatic carcinoma of fasting insulin levels falls in range of >6.10μU/ml. The highest insulin levels (>6.10μU/ml) were seen to be associated with an 2.55 fold risk of prostatic carcinoma when compared with fasting insulin levels of (<2.75 μU/ml). CONCLUSIONS Elevated fasting levels of serum insulin appear to be associated with a higher risk of prostate cancer.

Serum amyloid a as an independent prognostic factor for renal cell carcinoma--a hospital based study from the Western region of Nepal.

OBJECTIVE The objective of our present study was to assess the role of serum amyloid A (SAA) in stages and prognosis of renal cell carcinoma. MATERIAL AND METHODS It was a hospital based retrospective study carried out in the Department of Medicine and Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between 1st January 2008 and 31st December 2011. The variables collected were SAA, CRP. Approval for the study was obtained from the institutional research ethical committee. Quantitative analysis of human SAA and C-reactive protein (CRP) was performed by radial immune diffusion (RID) assay for all cases. RESULTS Of the 422 total cases of renal cell carcinoma, 218 patients had normal and 204 abnormal SAA. SAA levels were grossly elevated in T3 stage (122.3±SD35.7) when compared to the mean for the T2 stage (84.2±SD24.4) (p value: 0.0001). Similarly, SAA levels were grossly elevated in M1 stage (190.0±SD12.7) when compared to the M0 stage (160.9±SD24.8) (p: 0.0001). There was no significant association with elevated CRP levels (209.1±SD22.7, normal 199.0±SD19.5) . CONCLUSION The validity of SAA in serum as being of independent prognostic significance in RCC was demonstrated with higher levels in advanced stage disease.

Elevated Serum Insulin is an Independent Risk Factor for Hepatocellular Carcinoma: A Case Control Study from Nepal

AIM To investigate associations of fasting insulin and glucose levels in serum with hepatocellular carcinoma risk. MATERIALS AND METHODS This hospital based study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Nepalese Army Institute of Health Sciences, between 1st December, 2011 and 31st June, 2013. The variables collected were age, fasting plasma glucose, fasting plasma insulin and ALT. Quantitative determination of human insulin concentrations was accomplished by chemiluminescence enzyme immunoassay. RESULTS Of the total 220 subjects enrolled in our present study, 20 cases were of HCC and 200 were healthy controls. The maximum number of cases of hepatocellular carcinoma in category cutpoints of fasting insulin levels fell in the range of >6.10 μU/ml. The highest insulin levels (>6.10 μU/ml) were seen to be associated with an 2.36 fold risk of HCC when compared with fasting insulin levels of (<2.75 μU/ml). Furthermore, the insulin levels (2.75-4.10 μU/ml) of category cutpoints also conferred a 1.57 fold risk for HCC when compared with lowest fasting insulin levels of (<2.75 μU/ml). CONCLUSIONS The effect of an insulin level in increasing HCC risk appeared consistent, influencing incidence, risk of recurrence, overall survival, and treatment-related complications in HCC patients.

Diabetes Mellitus and Renal Cell Carcinoma - A Hospital Based Study from Kathmandu Valley

OBJECTIVE To diagnose renal cell carcinoma at early stages and for better prognosis , the main objective of our current study was to understand any association with diabetes with relation to age, gender, history of disease, diabetic laboratory parameters, tumor size and grade. MATERIALS AND METHODS This hospital based study was carried out using data retrieved from the register maintained in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between 1st December, 2011 and 31st May, 2012. The variables collected were age, gender, HbA1c, serum creatinine, fasting blood glucose. One way ANOVA was applied to examine statistical significance of differences between groups. The LSD post hoc test was used for the comparison of means of case groups. RESULTS Of the total 140 cases of renal cell carcinoma, 79 patients were also suffering from diabetes mellitus. The number of females (47) was more in diabetic RCC patients when compared to males (32). Significance was observed in levels of serum creatinine for tumor size >10 cm (0.0001*). The highest value of glycated hemoglobin (8.9%) and fasting blood sugar(148.3mg/dl)in cases of renal cell carcinoma along with diabetes mellitus was found in tumour size of 1-5 cm. CONCLUSION Diabetes mellitus has independent prognostic significance in RCC in relation to tumour size and grade.

Significance of CA19-9 in Predicting the Prognosis of Urothelial Carcinoma: A Hospital Based Study from Nepal

BACKGROUND The present study was undertaken to establish any correlation of elevated levels of CA19-9 with tumor stage or grade of urothelial carcinoma. MATERIALS AND METHODS This hospital based study was carried out in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between 1st July 2012 and 31st December 2012. Approval for the study was obtained from the institutional research ethical committee. CA19-9 was assayed with an ELISA reader for all cases and expressed in U/ml with 37U/ml taken as the cut-off upper value for normal. RESULTS Out of 20 cases enrolled, 15 were of urothelial carcinoma and the remaining 5 were controls. There was marked difference between the mean values of CA19-9 in cases 40.2±19.3U/ml of urothelial carcinoma and controls 7.98±7.34U/ml. The number of cases in Ta, TI, T2, T3, T4 stages of urothelial carcinoma were 2, 6, 3, 3, 1 respectively. The percentage rise in CA19-9 was less with low grade tumors (22.2%) when compared with high grade tumors (66.6%) (p value 0.001*). The percentage of rise in CA19-9 for muscle invasive tumors was very high when compared to superficial tumors. Similarly, the percentage of rise in CA19- 9 for metastatic disease was very high when compared to non-metastatic disease and it was found statistically significant (p value 0.001*). CONCLUSION Serum CA19-9 levels predicts the prognosis of urothelial carcinoma as it is almost invariably raised in tumors having metastatic spread.

Des-Gamma-Carboxyprothrombin for Early Identification and Prognosis of Hepatocellular Carcinoma - A Case Control Study from Western Nepal

OBJECTIVE To assess the diagnostic and prognostic value of AFP and des-gamma-carboxyprothrombin (DCP) in combination and alone for hepatocellular carcinoma. MATERIALS AND METHODS A case control study carried out in the Department of Biochemistry of Manipal College of Medical Sciences, Pokhara, Nepal between 1st January 2010 and 31st December 2011. The variables collected were age, gender, BMI, total proteins, albumin, AST, ALT, total bilirubin, DCP, AFP. Approval for the study was obtained from the institutional research ethical committee. Estimation of AFP was performed by ELISA reader for all cases. Analysis was done using descriptive statistics and confidence interval (CI). The data was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. RESULTS The mean age of HCC cases was 53.6±14.93 yrs. The percentage of females was less than males in both cases (23%) and controls (29%). The specificity of DCP reached 100% when its values was equal or greater than 150 (MAU/ml) for 0, 3, 6, 9, 12 months preceding the diagnosis of HCC. Similarly, the specificity for AFP was also nearly 100% when its value was equal or greater than 200 ng/ml 0, 3, 6, 9, 12 months earlier to the finding of HCC. The specificity of DCP (≥40 MAU/mL) and AFP(≥20 ng/mL) in combination was 93%, 97%, 95%, 96%, 97% in respect to 0, 3, 6, 9, 12 months prior to the diagnosis of HCC. CONCLUSION The combination of both DCP and AFP will improve the finding of initial HCC and the sensitivity of these markers was utmost at the time of HCC identification and noticeably lesser at former time points.

Prostate Biomarkers with Reference to Body Mass Index and Duration of Prostate Cancer

OBJECTIVE This study was performed to assess prostate biomarkers with reference to body mass index and duration of prostate cancer. MATERIALS AND METHODS A hospital based retrospective study was undertaken using data retrieved from the register maintained in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2009 and 28th February, 2012. Biomarkers studied were prostate specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γGT). Demographic data including age, duration of disease, body weight, height and body mass index (BMI) were also collected. Duration of disease was categorized into three groups: <1 year, 1-2 years and >2 years. Similarly, BMI (kg/m2) was categorized into three groups: <23 kg/m2, 23-25 kg/ m2 and >25 kg/m2. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. RESULTS Out of 57 prostate cancers, serum level of PSA, ACP and PAP were increased above the cut-off point in 50 (87.5%), 30 (52.63%) and 40 (70.18%) respectively. Serum levels of PSA, ACP and PAP significantly declined with the duration of disease after diagnosis. We observed significant and inverse relation between PSA and BMI. Similar non-signficiant tendencies were apparent for ACP and PAP. CONCLUSIONS Decreasing levels of prostate biomarkers were found with the duration of prostate cancer and with increased BMI. Out of prostate biomarkers, PSA was found to be significantly decreased with the duration of disease and BMI.

Significance of HCG to Distinguish Parathyroid Carcinoma from Benign Disease and in Adding Prognostic Information: A Hospital Based Study from Nepal

OBJECTIVE To differentiate between benign and malignant hyperparathyroidism on the basis of excretion of HCG and its malignant isoforms in urine. MATERIALS AND METHODS This hospital based study was carried out using data retrieved from the register maintained in Manipal Teaching Hospital from 1st January, 2008 and 31st August, 2012. The variables collected were urinary HCG and HCG malignant isoform, calcium and parathyroid hormone. Preceding the study, approval was obtained from the institutional research ethical committee. Analysis was by descriptive statistics and testing of hypothesis. A p-value of <0.05 (two-tailed) was used to establish statistical significance. RESULTS Out of the 20 cases, 10 were primary hyperparathyroidism and the remainder were parathyroid carcinomas. The urinary HCG 6.1∓0.6 fmol/mgCr was with in normal range in benign hyperthyroidism but was markedly elevated in three cases of malignant hyperparathyroidism (maximum value of excretion in urine for HCG was 2323 fmol/mgCr). The excretion of malignant isoform of HCG in urine was 0 in benign hyperparathyroidsm and in four cases of malignant hyperparathyroidism which fell into the category of persistantly low HCG. The maximum excretion of the malignant isoform of HCG in urine was 1.8, in the category of very high HCG. Calcium and parathyroid hormone were mildly raised in benign parathyroidism, while parathyroid hormone was markedly elevated in cases of malignant hyperparathyroidism falling into the category of very high HCG. CONCLUSIONS The excretion of urinary HCG in urine has the ability to distinguish between parathyroid adenomas and carcinomas and thus has potential to become a marker of disease progression in malignant parathyroid disease.

Association of type II diabetes mellitus with hepatocellular carcinoma occurrence--a case control study from Kathmandu Valley.

OBJECTIVE To assess associations of Type II DM with hepatocellular carcinoma occurrence in Nepal. MATERIALS AND METHODS This case control study was carried out using data retrieved from the register maintained in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between 1st January, 2012, and 31st August, 2012. The variables collected were age, gender, HbA1c. All biochemical parameters were analyzed in the Central Laboratory of our hospital by standard validated methods. One way ANOVA was used to examine the statistical significant difference between groups with the LSD post-hoc test for comparison of means of case groups. Odds ratios (OR) were calculated using simple logistic-regression analysis. RESULTS Etiological factors for HCC were HBV, HCV, alcohol and cryptogenic cirrhosis. The highest age group belonged to the etiological category of HCV with a mean of 71.9 ± 3.6 (CI 69.3, 74.5) years and the lowest age group to the etiological category of HBV with 61.7 ± 5.3(CI 57.9, 65.5) years. The main imperative basis of HCC in present study was HCV (39.5%) and second most significant cause of HCC was alcohol (26%). Glycated hemoglobin was found to be more in males with HCC (7.9%) as compared to females (7.3%). The percentage of Type II diabetes mellitus was greater in HCC patients when compared to controls. This difference was statistically significant with an odd ratio of 4.63 (p<0.001). CONCLUSION Type II DM influences incidence, risk of recurrence, overall survival, and treatment-related complications in HCC patients.