Hilal Ahmad Wani

ROLE OF HEMATOLOGICAL PARAMETERS IN DIAGNOSIS AND PROGNOSIS OF GASTRI C CARCINOMA IN KASHMIR , INDIA

Gastric cancer is the second leading cause of death in the world . More than two - thirds of the patients are dia gnosed at an advanced stage. Metastatic gastric cancer has poor prognosis with a median 5 years - survival rate of 7 %. Hematological parameters including leukocyte count, platelet count and their ratios have been used as prognostic indicators in several tum or types. The aim of the study was to examine an association of the difference in haematological parameters between gastric cancer patients and normal controls of Kashmir valley. We enrolled 210 subjects of which 110 were newly diagnosed gastric cancer ca ses and 100 were healthy controls. Participants were re cruited from hospitals, clinics and radiology department of Sh ri Maharaja Hari Singh ( SMHS) hospital Srinagar, India from May 2011 to Apr 2012 . After informed consent, all patient s were interviewed and examined and demographic and clinical information was collected. Blood samples were drawn for examination of hematological measures and for measurement of carcino embryonic antigen (CEA) . W e found the hematological parameters like: Hb (10 ± 2, P = 0.004 ) , MCV (84.25 ± 5, p = 0.01), Granulocyte % (70.04 ± 10.63, p = 0.001), Lymphocyte % (26.12 ± 10.7, p < 0.0001) , RDW (48 ± 10, p = 0.004 ) in gastric cancer patients and these were found to be highly decreased as compared to normal healthy controls where hema tological paramete rs was in normal range . Our study was statistically significant (p < 0.005). The study suggests that the hematological parameters like HB, MCV, Granuloc yte %, Lymphocyte % and RDW are de creased in gastric cancer patients and acts as a n ea rly marker in the prognosis and diagnosis of gastric cancer.

Polymorphism of the XRCC3 gene and risk of gastric cancer in a Kashmiri population: a case-control study.

DNA repair plays a critical role in protecting the genome of the cell from the insults of cancer-causing agents. Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with the risk of developing cancer. Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity and genetic susceptibility to different cancers. The X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3) gene is a member of the RAD51 gene family. It encodes an important protein that functions in the homologous recombination repair of a DNA double-strand break. For gastric cancer, the importance of mutations in mismatch repair genes has been well documented, but less is known about other DNA repair pathways in gastric carcinogenesis. In this study, we have focused on the XRCC3 gene, involved in homologous recombinational repair. The Kashmir valley has an increased incidence of gastric cancer and its etiology has not been understood fully as yet. As the Kashmiri population is ethnically and demographically different from that in other parts of the world, the aim of this study was to determine whether a single nucleotide polymorphism of the XRCC3 gene (Thr241Met) of exon 7 can influence the risk of gastric cancer in the population. As many as 80 histopathologically confirmed gastric cancer cases and 70 healthy controls, age, sex, and ethnicity matched for known genotypes of XRCC3 exon 7 were studied. We genotyped for this variant using PCR-restriction fragment length polymorphisms. The XRCC3 genotype and allele frequencies were not significantly different between cases and controls (P=0.92 for the genotype; P=0.72 for the allele). The XRCC3 241Met allele frequency (6.6%) was significantly lower in healthy Kashmiri controls than reported previously in healthy US White controls (38.9%). Compared with the XRCC3 241Thr/Thr genotype, the variant XRCC3 241Thr/Met and Met/Met genotypes were not associated with an increased risk of gastric cancer (adjusted odds ratio=1.19; 95% confidence interval=0.44–3.18). These findings suggest that polymorphisms of XRCC3 Thr241Met may not play a role in the etiology of gastric cancer. Further studies with a larger number of participants and simultaneous measurement of different polymorphisms in DNA repair genes in the same pathway are needed.

Type 2 diabetes and metabolic syndrome – adipokine levels and effect of drugs

Abstract Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is also characterized by changes in various adipokines. In this study, our objective was to estimate the levels of adiponectin, leptin, and resistin (ALR) in T2DM patients, besides studying the effect of various drugs on their levels. Study participants included 400 diabetic and 300 normal patients from the Department of Endocrinology and Department of Biochemistry, Govt Medical College Srinagar. Subjects were categorized under various groups, i.e., Group 1 (metformin treated) and Group 2 (glimepiride treated), and cases were also categorized as obese with T2DM (Group A), obese without T2DM (Group B), and T2DM only (Group C). The serum ALR levels were estimated by ELISA (Alere), and biochemical parameters were also evaluated before and after treatment. Adiponectin levels were found to be significantly lower in T2DM cases as compared to controls (12 ± 5.5 versus 22.5 ± 7.9 μg/ml), while leptin and resistin levels were found to be significantly higher than controls (14.3 ± 7.4 versus 7.36 ± 3.73 ng/ml) (13.4 ± 1.56 versus 7.236 ± 2.129 pg/ml). Taking the effect of drugs into consideration, the effect on adiponectin and resistin levels was found to be highly significant in Group 2 before and after treatment (11 ± 5 versus 19.2 ± 4.5 μg/ml) (13.6 ± 2.5 versus 7.3 ± 2.9 pg/ml), while more effect was observed in leptin among Group 1 (metformin)-treated cases (27 ± 15 ng/ml versus 15 ± 15 ng/ml). Further the adiponectin levels were found to be significantly lower in Group B, while leptin and resistin levels were found to be significantly higher among obese cases when compared to T2DM cases only. Glimepiride also shows more effect on FBG, HbA1c% levels, while metformin shows more effect on Lipid profile levels. From the study, it can be concluded that ALR levels are affected by use of antidiabetic drugs among which glimepiride shows more effect on adiponectin and resistin levels, while leptin gets affected more by metformin. It can also be proposed that ALR levels are not affected by diabetes only, suggesting that their alterations in T2DM may be due to obesity as we observed more ALR changes in obese cases when compared to T2DM cases, and so there might be an important link between adiposity and insulin resistance.

Diminished expression of MGMT & RASSF1A genes in gastric cancer in ethnic population of Kashmir

BACKGROUND Cancer initiation and progression are accompanied by profound changes in DNA. DNA methylation that was the first epigenetic alterations identified in cancer. DNA hypermethylation at promoter sites is closely associated with down regulation of protein and as major participant in the development and progression of series of human tumors. Therefore we hypothesized that promoter hypermethylation of RASSF1A & MGMT gene could influence susceptibility to gastric cancer (GC) as well, and we conducted this study to test the hypothesis in Kashmiri population. METHODS A hospital based case-control study; including 200 GC cases and 200 matched controls from patients who went surgical resection. Promoter hypermethylation was determined by Methylation Specific Polymerase chain reaction. The expression of MGMT & RASSF1A protein was examined by Western blotting technique. RESULTS Frequency of promoter region hypermethylation of MGMT gene were 46.5% in cases and 5.5% in controls (P<0.05) while as in case of RASSF1A frequency was 44% in cases and 4.5% in controls (P<0.05). Further, frequency of hypermethylation of both genes was found predominant in males, aged and advanced pathological stage subjects. Loss of MGMT expression was found in 46.5% cases (P<0.05) while as loss of RASSF1A expression was found in 40.5% cases (P<0.05). In both genes a positive correlation was observed between promoter CpG island hypermethylation and down regulation of respective proteins. CONCLUSIONS These findings indicate that promoter hypermethylation at CpG island may be responsible for reduction of expression at protein level which may be an initial event in carcinogenesis and the progression of GC.

Role of laparoscopy in nonspecific abdominal pain

Objective: The aim was to determine the role of laparoscopy in the management of nonspecific abdominal pain (NSAP). Background: NSAP constitutes a good proportion of surgical admissions, both in emergency and elective settings with considerable diagnostic dilemma. Patients and Methods: All patients who presented with pain abdomen with no immediate cause and were labeled as NSAP after clinical assessment and investigations and following that underwent laparoscopy to make a definitive diagnosis were included in the study. Results: A total of 88 patients were included in the study. There were 59 (67%) females and 29 (33%) males. The mean age was 26 years (range 18-58 year). The common mode of admission was out-patient department 69 (78.4%) patients. Twenty-five (28.4%) patients presented with NSAP in lower abdomen, followed by 21 (23.8%) with right lower abdominal pain and 19 (21.5%) with central pain radiating to right lower abdomen. Diagnosis was established in 75 (85.2%) patients. In 13 (14.7%) no pathology was found. The most common diagnosis was pathology of appendix in 29 (32.9%) patients followed by pelvic pathology in 18 (20.4%) and abdominal tuberculosis in 14 (15.9%) patients. Most 37 (42%) of the patients stayed in the hospital for 24 h. There was no readmission and no major postoperative complications. Conclusions: Laparoscopy has a definitive role in diagnostic dilemma associated with NSAP. It has at the same time role in treatment of the condition; hence laparoscopy has a diagnostic and a therapeutic implication in management of NSAP.

Preventive effect of tamsulosin on postoperative urinary retention in benign anorectal surgeries

Objective: The aim was to study the prophylactic effect of tamsulosin on postoperative urinary retention in benign anorectal surgeries. Background: Acute urinary retention (AUR) after anorectal surgeries is essentially a type of postoperative urinary retention (POUR). It is the most common complication of the procedure. Use of tamsulosin, a super selective alpha 1a adrenergic blocker has been found to reduce the risk of POUR. Patients and Methods: Patients who underwent anorectal surgeries for benign anorectal conditions were included in this study. Patients were randomly assigned into two groups. In one, group (cases), patients were given 0.4 mg of oral tamsulosin only 6 h preoperative and 6-8 h postoperatively. Inability/difficulty to pass urine, which necessitated catheterization after following patient for 24 h was labeled as POUR. Results: A total of 626 patients who underwent surgery for benign anorectal condition were included in the study and grouped into two groups with 313 patients in each group, control and case group. In the control group, 56 patients (17.9%) had inability to pass urine and required catheterization and in the case group, only eight patients (2.5%) needed catheterization following POUR. The difference in the requirement of catheterization following POUR was statistically significant (P = 0.04). Hemorrhoidectomy was the most common anorectal surgery associated with POUR. Conclusion: The use of tamsulosin in preoperative and postoperative period has been found effective to reduce the incidence of POUR following surgeries for benign anorectal pathologies.