Khursheed Alam Wani

Molecular Gate Keepers Succumb to Gene Aberrations in Colorectal Cancer in Kashmiri Population, Revealing a High Incidence Area

Background/Aim: Colorectal cancer (CRC) is one of the leading malignancies worldwide and has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The aim of this study was to identify p53 and K-ras gene mutations in CRC patients in a Kashmiri population, and to assess whether these mutations are linked with clinicopathological parameters. Materials and Methods: Paired tumor and normal tissue samples from a consecutive series of 53 patients undergoing resective surgery for CRC were prospectively studied for p53 and K-ras gene mutations by PCR/single strand conformation polymorphism (SSCP). Results: Less than half (45%, 19/42) of the patients presented mutations in the p53 gene. Twenty eight mutations were found in the p53 gene, which comprised of 23 substitutions (17 transitions + 6 transversions), and five insertions. The 23 substitutions constituted 18 missense mutations, two nonsense mutations, and three silent mutations. Of the 28 mutations (7.14%) observed in this study, 2 were not previously reported for CRC samples and were identified as novel p53 mutations. A few patients (22.64%, 12/53) presented with mutations in K-ras, constituting 13 missense mutations, out of which 11 were G→A transitions, one was a G→C transversion, and one a G→T transversion. More than half (61.5%) of the mutations occurred in codon 12 whereas a few (38.5%) occurred in codon 13. One tumor contained missense mutations in both codons. Comparison of the mutation profiles of our patients with those of other ethnic populations and regions reflected both differences and similarities, indicating co-exposure to a unique set of risk factors. Conclusion: Mutations of the p53 and K-ras genes are some of the most common genetic changes in the development of human CRC. The high frequency of p53 gene mutations implicates p53 as a predominant factor for CRC in the high-risk ethnic Kashmiri population.

Promoter Methylation Status of DNA Repair Gene (hMLH1) in Gastric Carcinoma Patients of the Kashmir Valley

Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in the capacity to repair mismatches in the genome, is an important factor in the development of gastric cancer (GC), for example. Epigenetic changes, including aberrant methylation of 5/CpG islands in the promoter regions of mismatch repair (MMR) genes like hMLH1, have been implicated in the development of various types of GC. In the present study we evaluated the role of hMLH1 promoter hypermethylation in Kashmiri GC patients and controls, and assessed correlations with various dietary and lifestyle factors. The study included 70 GC patients (56 males and 14 females; age (mean ± S.D) 50 ± 11.4 years). Distinction between methylated and unmethylated was achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due to promoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC cases than in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001). We also observed a statistically significant association between methylated hMLH1 gene promoter and smoking, consumption of sundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylation is strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in the Kashmir valley.

Secondary Tuberculosis of Breast: Case Report

Tuberculosis of breast is a rare disease which is difficult to differentiate from carcinoma of breast. The involvement of breast can be primary or secondary to some focus in body. A case of secondary tuberculosis of right breast in a 21-year-old female from Kashmir, India, is being reported. Presentation was as a painless discharging sinus of right breast. A tubercular foci of rib was the affecting source of disease. No other evidence of tuberculosis was present in the body. Resection of involved rib segment, along with the discharging sinus, was performed. The patient had antitubercular therapy for 9 months, with no recurrence seen in followup.

Long-term results of choledochoduodenostomy in benign biliary obstruction

AIM To determine the long-term results of choledochodudenostomy in patients with benign billiary obstruction. METHODS This prospective study was conducted at Sheri Kashmir Institute of Medical Sciences Srinagar Kashmir, India over a period of 10 years from January 1997 to December 2007. The total number of patients who underwent choledochoduodenostomy during this period was 270. On the basis of etiology of biliary tract obstruction, patients were divided into a calculus group, an oriental cholangiohepatitis group, a benign biliary stricture group and others. Patients were followed for a variable period of 13 mo to 15 years. RESULTS Choledochoduodenostomy (CDD) with duo-denotomy was performend in four patients. CDD with removal of T- tube, CDD with left hepatic lobectomy and CDD with removal of intra biliary ruptured hydatid was performed in three patients each. In the remaining patients only CDD was performed. Immediate post operative complications were seen in 63 (23%) patients, while long-term complications were seen in 28 (11%) patients, which were statistically significant. Three patients died during hospitalization while four patients died in the late post-operative period. CONCLUSION Our conclusion is that CDD is safe and produces good long term results when a permanent biliary drainage procedure is required.

Gastric Cancer in Young Patients

Aim. The aim of this study was to see the clinical, pathological, and demographic profile of young patients with stomach carcinoma besides association with p53. Patients and Methods. Prospective study of young patients with stomach carcinoma from January 2005 to December 2009. A total of 50 patients with age less than 40 years were studied. Results. Male female ratio was 1 : 1.08 in young patients and 2.5 : 1 in older patients. A positive family history of stomach cancer in the first degree relatives was present in 10% of young patients. Resection was possible only in 50% young patients. 26% young patients underwent only palliative gastrojejunostomy. The most common operation was lower partial gastrectomy in 68%. Amongst the intraoperative findings peritoneal metastasis was seen in 17.4% in young patients. 50% young patients presented in stage IV as per AJCC classification (P value .004; sig.). None of the patients presented as stage 1 disease in young group. Conclusion. Early detection of stomach carcinoma is very important in all patients but in young patients it is of paramount importance.

Impact of molecular alterations of BRAF in the pathogenesis of thyroid cancer.

BRAF alterations represent a novel indicator of the progression and aggressiveness of thyroid carcinogenesis. So, the main aim of the study was to elucidate the involvement of BRAF gene mutations and its expression in Kashmiri (North India) patients and investigate their association with clinico-pathological characteristics. Mutational analysis of BRAF gene was performed by polymerase chain reaction followed by DNA sequencing, whereas analysis of BRAF protein expression was done by western blotting. Overall mutations in BRAF was found to be 25% (15 of 60) and all of them were transversions (T>A) affecting codon 600 (valine to glutamine), restricted only to papillary thyroid cancer and well-differentiated grade. Patients with well-differentiated disease and in particular elevated thyroid-stimulating hormone levels were significantly associated with BRAF mutations (P < 0.05). Overall, 90% (54 of 60) of thyroid cancer cases showed increased expression of BRAF and non-smokers being significantly associated with BRAF over-expression. Totally, 86.7% (13 of 15) of BRAF mutation-positive patients were having over-expression of BRAF protein, whereas 91.2% (41 of 45) of patients with wild-type BRAF status were having over-expressed BRAF protein (P > 0.05). We conclude that both mutational events as well as over-expression of BRAF gene is highly implicated in pathogenesis of thyroid cancer and the BRAF protein over-expression is independent of the BRAF mutational status of thyroid cancer patients.

The XRCC1 Arg399Gln Gene Polymorphism and Risk of Colorectal Cancer: a Study in Kashmir

BACKGROUND The DNA repair gene XRCC1 Arg399Gln gene polymorphism has been found to be implicated in the development of various cancers, including colorectal cancer (CRC), in different populations. We aimed to determine any association of this polymorphism with the risk of CRC in Kashmir. MATERIALS AND METHODS A total of 120 confirmed cases of CRC and 146 healthy cancer free controls from the Kashmiri population were included in this study. Genotyping was carried out by the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. RESULTS Genotype frequencies of XRCC1 Arg399Gln observed in controls were 34.2%, 42.5% and 23.3% for GG (Arg/Arg), GA (Arg/Gln), AA( Gln/Gln), respectively, and 28.3%, 66.7% and 5% in cases, with an odds ratio (OR)=5.7 and 95% confidence interval (CI) =2.3-14.1 (p=0.0001). No significant association of Arg399Gln SNP with any clinicopathological parameters of CRC was found. CONCLUSIONS We found the protective role of 399Gln allele against risk to the development of CRC. The XRCC1 heterozygote status appears to be a strong risk factor for CRC development in the Kashmiri population.

Primary paraspinal hydatid cyst: A rare presentation of Echinococcosis

Hydatid disease is endemic in most cattle rearing areas, particularly Australia, New Zealand, Mediterranean countries, India, Africa and South America.1,2 It is often manifested by a slowly growing cystic mass, with hepatic and pulmonary involvement being most common.3 Unusual sites of involvement frequently cause diagnostic problems and hence delay in diagnosis and many serious complications. Primary skeletal muscle involvement is very rare.4,5 We present a case of hydatid disease of lumbar paraspinal muscles in a middle aged female, who presented to the General Surgery clinic at our Institute.

Low molecular weight heparin in prophylaxis of deep vein thrombosis in Asian general surgical patients: A Kashmir experience

Background and Objectives: Deep vein thrombosis (DVT) occurs at a lower rate in Asia than in the rest of the world. We wanted to study the significance and efficacy of low molecular weight heparin (LMWH) in prophylaxis of DVT in major general surgical patients in the Kashmir Valley (India, Asia) so as to make it a routine in our patients. Patients and Methods: This was a prospective study in which the effect of LMWH was compared with no prophylaxis. Results: LMWHs are more effective than no prophylaxis in the prevention of DVT and pulmonary thromboembolism in highest-risk general surgical patients (odds ratio = 16.64; 95% confidence interval = 3.63–1130.03; P-value = 0.014). Conclusion: LMWHs have a significant prophylactic effect on DVT in general surgical patients, with a higher benefit to risk ratio, and, in spite of the low incidence of DVT in Asia, its prophylaxis should routinely be considered in this part of the world as well, preferably in the form of LMWHs.

Evaluating a conservative approach to managing liver injuries in Kashmir, India

Aim: There has been a steep rise in incidence of liver injury in the past few years because of increase in incidence of road traffic accidents. The aim of this study was to evaluate the role of non-operative management of liver injury due to blunt abdominal trauma. Materials and Methods: All patients with liver injury from blunt trauma abdomen were studied between January 2000 and January 2010. A total of 152 patients with liver injury were put on conservative management. Hundred and three (67.77%) patients were males and 49 (32.23%) were females with an age range of 15-60 years (32.8 years). Most of the injuries were because of road traffic accidents (81.57%). Liver injuries were graded according to Moores classification using computed tomography. Patients with Grade V and VI were excluded from the study. Patients who were unstable hemodynamically on admission were also excluded from the study. Results: There was no mortality in our series. Eight patients needed exploration because they developed hemodynamic instability. Four of the patient developed post-operative liver abscess which was treated conservatively. Conclusion: Non-operative management of liver injury due to blunt trauma abdomen is a safe, effective and treatment modality of choice in hemodynamically stable Moores grade I to Grade IV injury.