IL-1ß polymorphism and expression associated with decreased risk of gastric carcinoma: a case control study in the ethnic Kashmiri population, India.

The aim of this research was to investigate the possible association between gastric carcinoma (GC) and polymorphisms of the IL-1ß gene in the Kashmiri population using peripheral blood DNA from 150 gastric carcinoma cases and 250 population controls with detailed data for clinicopathological characteristics of the disease. Two SNPs in the IL-1ß gene were selected for this study. Expression of IL-1ß was studied in 50 gastric carcinoma cases using immunohistochemistry and RT-PCR and then correlated with genotype. The frequency of the IL-1ß-511 C allele was significantly higher in the GC case group (53.3%) than in controls (45.4%) with an odds ratio (OR) of 0.73 and a P value of 0.03. Multivariate regression analysis showed associations of gastric carcinoma with mutant form of IL-1ß-511 TT (OR 0.309; P value <0.001) and the CC genotype of IL-1ß-31 (OR 0.313; P value of 0.002). Haplotype analysis of IL-1ß-31 and IL-1ß-511 showed decreased association of IL- 1ß-31 T with IL-1ß-511 C with gastric carcinoma (OR 0.728; P value 0.03). Expression study of 50 samples by immunohistochemistry (IHC) and RT-PCR showed association with grade III and stage III+IV. After correlating the expression with polymorphism no association was found.

H. pylori infection, inflammation and gastric cancer.

INTRODUCTION: A strong association between chronic infection, inflammation, and cancer has been suggested. DISCUSSION: Helicobacter pylori, a microaerophilic gram negative bacterium, infects about half the world's population. It has been defined as a definitive carcinogen in the pathogenesis of gastric cancer. H. pylori evades the host immune responses and persists in the stomach leading to gastritis gastric atrophy and sometimes gastric cancer. CONCLUSION: Chronic H. pylori infection causes gastric cancer via two mechanisms: the presence of virulence factors and the induction of chronic inflammation which ultimately leads to neoplastic transformation.

CagA subtyping in Helicobacter pylori isolates from gastric cancer patients in an ethnic Kashmiri population.

UNLABELLED: The association between gastric cancer and Helicobacter pylori has been well established. Among H. pylori virulence genes the most important determinant is the cytotoxin associated antigen gene (cagA) which is characterized by the presence of repeated EPIYA motifs at the C terminus of the protein. From the alignment and number of these EPIYA motifs, two major types of CagA protein have been identified. AIMS: The aim of this study was to classify the CagA into eastern or western type and to determine the number and type of motifs present. METHODS: The CagA subtyping was done by PCR and multiplex PCR for eastern/western classification and determination of EPIYA motifs respectively. RESULTS: All the isolates studied were of the western type, with 70% of the isolates having more than one EPIYA-C motifs. No statistically significant association was found between the presence of CagA and more than one EPIYA-C motifs with the clinical outcome (differentiation status of the tumour).

Study of TLR4 and IL-8 gene polymorphisms in H.pylori-induced inflammation in gastric cancer in an ethnic Kashmiri population.

BACKGROUND: TLRs play an essential role in the initial handling of H. pylori and determine the clinical outcomes that range from simple asymptomatic gastritis to peptic ulcer disease and gastric cancer. Asp299Gly and Thr399Ile polymorphisms in TLR4 have been associated with a variety of inflammatory and infectious conditions including gastric cancer. The T-251A polymorphism in the promoter region of IL-8 gene has been found to be associated with changing the in vitro levels of IL-8 production. IL-8 exhibits angiogenic activity and is responsible for tumor-associated angiogenesis in several cancers. MATERIALS AND METHODS: 130 gastric cancer patients and 200 healthy controls were included in this study. DNA extraction was followed by PCR detection of H. pylori infection, PCR-RFLP for the TLR 4 polymorphism and PCR-CTPP for IL-8 gene polymorphism. RESULTS: The adjusted OR for gastric cancer risk was 1.15 (95% CI, 0.8357-1.3463); 1.39 (0.6964-2.781) and 1.43 (0.954-2.1515) for Asp299Gly, Thr399Ile and IL-8 T_251A respectively. Odds Ratio analysis showed CT genotype and AT and AA genotypes as risk factors for the development of gastric cancer. We found the Asp299Gly polymorphism carrier to be significantly associated (p value 0.03)with the development of tumours in the distal part of the stomach and Thr399Ile polymorphism to be significantly associated(p value 0.008) with the development of well-differentiated gastric adenocarcinoma.The IL-8 T-251A polymorphism was not found to be associated with any of the clinicopathological characteristics. DISCUSSION: No correlation was found between the appearance of disease and HP infection or the presence of TLR4 and IL-8 gene polymorphisms and HP infection.

Comparative study of hemorrhoidectomy and rubber band ligation in treatment of second and third degree hemorrhoids in kashmir.

The diagnosis of hemorrhoids is primarily based on the proctoscopic examination. The study evaluates comparative results of rubber band ligation (RBL) and hemorrhoidectomy. This study was conducted over a period of 1½ year from Jan 2003 to June 2004. It includes 100 patients having second- or third-degree primary hemorrhoids who attended surgical OPD of SMHS Hospital Srinagar, Kashmir. These 100 patients were selected randomly and divided into two groups of 50 patients each (hemorrhoidectomy group and RBL group). Each patient was subjected to sigmoidoscopy to exclude other lesion higher up in rectosigmoid. Patients of fissure, fistulae, and malignancy were excluded. All parameters were recorded and finally analysed. The statistical analysis of the study was done using SPSS statistical package in which we used descriptive statistics and correlation analysis for the final evaluation. Hemorrhoidectomy and RBL are equally effective especially in second-degree hemorrhoids. However, RBL should be considered the first-line treatment in second-degree hemorrhoids because being an outpatient procedure, it is cost effective for the patients, saves many a hospital beds for more sick patients, and takes the pressure off the surgical waiting list. Although RBL is not as effective as hemorrhoidectomy in third-degree hemorrhoid, it does improve bleeding and prolapse and is highly recommended for patients who are unfit for surgery or have concurrent disease that contraindicates anesthesia. RBL should be considered as the first-line treatment for second-degree hemorrhoid. However, in the third-degree hemorrhoids, hemorrhoidectomy achieves better results, and RBL is recommend as the first-line treatment for those patients in whom there is contraindication for surgery or anesthesia.

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 Moore's 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 Moore's grade I to Grade IV injury.

Papillary carcinoma thyroid with metastasis to ectopic cervical thymus.

Papillary carcinoma of thyroid is the most common type of thyroid neoplasm which is usually confined to the thyroid and tends to metastasize to regional lymph nodes. Distant metastasis occur in up to 15% of cases. Thymic metastasis from any malignant carcinoma is extremely rare with only four cases reported in medical literature. We report a case of papillary carcinoma of thyroid metastasizing to ectopic cervical thymus which has not been previously reported.

P66shc and its downstream Eps8 and Rac1 proteins are upregulated in esophageal cancers.

Members of Shc (src homology and collagen homology) family, p46shc, p52shc, p66shc have known to be related to cell proliferation and carcinogenesis. Whereas p46shc and p52shc drive the reaction forward, the role of p66shc in cancers remains to be understood clearly. Hence, their expression in cancers needs to be evaluated carefully so that Shc analysis may provide prognostic information in the development of carcinogenesis. In the present study, the expression of p66shc and its associate targets namely Eps8 (epidermal pathway substrate 8), Rac1 (ras-related C3 botulinum toxin substrate1) and Grb2 (growth factor receptor bound protein 2) were examined in fresh tissue specimens from patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma using western blot analysis. A thorough analysis of both esophageal squamous cell carcinoma and adenocarcinoma showed p66shc expression to be significantly higher in both types of carcinomas as compared to the controls. The controls of adenocarcinoma show a higher basal expression level of p66shc as compared to the controls of squamous cell carcinoma. The expression level of downstream targets of p66shc i.e., eps8 and rac1 was also found to be consistently higher in human esophageal carcinomas, and hence correlated positively with p66shc expression. However the expression of grb2 was found to be equal in both esophageal squamous cell carcinoma and adenocarcinoma. The above results suggest that the pathway operated by p66shc in cancers does not involve the participation of Ras and Grb2 as downstream targets instead it operates the pathway involving Eps8 and Rac1 proteins. From the results it is also suggestive that p66shc may have a role in the regulation of esophageal carcinomas and represents a possible mechanism of signaling for the development of squamous cell carcinoma and adenocarcinoma of esophagus.

Closure of the Common Duct -Endonasobiliary Drainage Tubes vs. T Tube: A Comparative Study.

For the last century T tube drainage of the bile duct has remained standard practice following choledochlithotomy. It vents the biliary tree, provides route for cholangiography and management of residual stones. However, T tubes are associated with significant complications. This retrospective study compared the use of Endonasobiliary drainage tubes and the T tube in 66 patients who underwent open choledocholithotomy for effectiveness and complications. Both groups were statistically comparable. Only 15.15% patients in the Endonasobiliary drainage group, while 45.45% patients in the T tube group developed complications. Severe complications such as biliary peritonitis and intraperitoneal collections were noted only in the T tube group. The Endonasobiliary drainage tube was removed significantly earlier and patients from this group were discharged earlier as compared to those in the T tube. The Endonasobiliary drainage tube is as effective as the T tube in postoperative biliary drainage and allows cholangiograms to be performed. Its use is associated with less complications and it can be removed safely earlier than the T tube. Thus patients have a shorter time with tubes and can be discharged home earlier.

Primary closure of the common duct over endonasobiliary drainage tubes.

The T-tube remains the standard method of intraductal drainage after open choledochotomy for choledocholithiasis. We studied the use of an endonasobiliary drainage (ENBD) tube as an alternative to the T-tube for postoperative intraductal drainage. A series of 20 patients with documented choledocholithiasis in whom endoscopic methods of stone retrieval failed to clear the common bile duct (CBD) were selected for the study. All patients had ENBD tubes placed preoperatively at endoscopic retrograde cholangiopancreaticography and then were subjected to open choledocholithotomy with primary closure of the choledochotomy over the ENBD. The age of the patients in the study group ranged from 18 to 75 years. Three patients (15%) had acute cholangitis at the time of surgery. Stones were confirmed at surgery in 85% of the patients, and the size of the CBD was found to range from 1.0 to 2.3 cm. All 20 patients underwent closure of the common duct over an ENBD tube without any difficulty. None of the patients experienced biliary complications such as bile leaks, biliary peritonitis, biliary fistula, pancreatitis, or cholangitis. No patient had any residual stone as documented by postoperative cholangiograms. Abdominal drains remained in place for 2 to 4 days, and the ENBD tubes were removed between days 6 and 8. The length of the postoperative hospital stay varied from 7 to 15 days, with 65% of the patients going home before postoperative day 8.

Primary extrahepatic abdominal hydatidosis.

INTRODUCTION: Most of the abdominal hydatid cysts occur in liver. Extrahepatic hydatid cyst is usually secondary to rupture (operative and non-operative) of the hepatic hydatid cyst. Primary extrahepatic hydatid cysts are rare and only a few sporadic cases have been reported. MATERIAL AND METHODS: One hundred and eighty-three patients with abdominal hydatid cysts managed surgically from January 1998 to December 2003 were evaluated retrospectively. Twelve (6.5%) patients had only extrahepatic abdominal involvement. RESULTS: The cysts were present in spleen (2.2%), pancreas (1.1%), peritoneum and pelvis (1.6%), gallbladder (0.6%), mesocolon (0.6%) and adrenal (0.6%). DISCUSSION AND CONCLUSIONS: It is difficult to diagnose extrahepatic echinococcosis as it usually is not suspected. Symptoms are related to size, location or ensuing complication of the cyst. It should be strongly suspected in differential diagnosis of all abdominal cysts especially in an endemic area.