Predictors of Rebleeding in Non-variceal Upper Gastrointestinal Bleeding of Peptic Ulcer Etiology in Kashmiri Population.

Background Upper gastrointestinal bleeding (UGIB) represents a substantial clinical and economic burden and rebleeding is one of the most important predictors of morbidity and mortality. Identifying patients who are likely to rebleed is a critical component of effectively managing patients with bleeding peptic ulcers. So, the study was undertaken to look for predictors of rebleeding in patients with bleeding peptic ulcers and try to find out the new scoring system to predict rebleeding in our population. Material and methods A retrospective analysis of prospectively maintained hospital data of UGIB patients was done and 480 patients of endoscopically documented peptic ulcers whose complete data was available were taken for study. Results Among the studied patients, men constituted 84.6%, and most of the patients were in the third to sixth decade of life with a mean age of 40.9±15.9 years, 76% were from rural areas. Only males with a mean age of 38.4±19.8 rebled with a rebleeding rate of 2.9% only. Half of the patients who rebled were in shock at the time of presentation. Those who rebled received more units of blood transfusion (mean 3±1.8), had a large mean ulcer size of Forest class IIa and IIb and epinephrine injection monotherapy group with varied statistical significance. Among rebleeders (n=14), eight patients were managed by a second endoscopic therapy, and six (42.8%) rebleeders and 1.25% of patients in total needed surgery. Two patients ultimately died giving overall mortality of 0.4% and mortality of 14.3% among rebleeders. Conclusion Our study found a very low rebleeding rate and mortality which could be explained by a young population with fewer co-morbidities and better response to proton pump inhibitor therapy. The significant parameters related to rebleeding were shock at presentation, degree of smoking, units of blood transfused, ulcer size, and high-risk endoscopic stigmata.

CYP1A2*1F Gene Variant, Alkaline Salt Tea Intake and Risk of Esophageal Squamous Cell Carcinoma.

Unlike many other cancers, the relationship of CYP1A2*1F (rs762551) polymorphism with esophageal squamous cell carcinoma (ESCC) risk has not been assessed so far. To evaluate its association with ESCC, we conducted a case control study in Kashmir, India, a high risk region. We recruited 404 histopathologically confirmed ESCC cases and 404 controls, individually matched for sex, age and residence to the respective cases. Information was obtained on dietary, lifestyle and environmental factors in face to face interviews using a structured questionnaire from each subject. Genotypes were analyzed by polymerase chain reaction, restriction fragment length polymorphism and sequencing randomly selected samples. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that mutant genotype (AA) of CYP1A2*1F polymorphism was associated with ESCC risk (OR = 3.11; 95% CI: 1.72-5.36). A very strong ESCC risk was observed in subjects who drank >1250 ml of salt tea daily and harbored mutant genotype of CYP1A2*1F (OR = 14.51; 95% CI: 5.33-39.47). The study indicates that CYP1A2*1F polymorphism is associated with ESCC risk and the risk is modified in salt drinkers. However, more replicative and mechanistic studies are needed to substantiate the findings.

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.

Cyclin D1 G870A polymorphism and risk of colorectal cancer: a case control study.

The present study aimed to analyse the role of cyclin D1 A870G polymorphism in modulating the susceptibility to colorectal cancer (CRC) in the Kashmiri population. The genotype distribution of the cyclin D1 gene in 130 CRC cases in comparison with 160 healthy controls was investigated. No direct significant association between cyclin D1 genotypes and CRC was observed; however, the AG and AA genotypes were found to be associated with an increased risk of CRC compared to the GG genotype, with an almost 2-fold increase in OR. This study suggests that the cyclin D1 polymorphism is associated with an increased risk of CRC in the Kashmiri population.

Emergency pancreaticoduodenectomy in duodenal paraganglioma: case report.

Duodenal gangliocytic paraganglioma (DGP) is a rare tumor that characteristically occurs in the second part of duodenum. These appear as submucosal masses that protrude into the lumen of a duodenum. Gastrointestinal bleeding is the commonest manifestation of DGP. Metastatic spread to regional lymph nodes occurs rarely. Surgical resection is the treatment of choice for DGP. A case of a DGP is reported in young female who presented with a recurrent upper gastrointestinal bleeding. Upper gastrointestinal endoscopy (UGIE) documented a mass in the ampullary region with ulceration in its middle which was bleeding. Recurrent gastrointestinal bleeding necessitated an emergency pancreaticoduodenectomy. Histopathology of specimen documented gangliocytic paraganglioma.

Effect of bending exercise on gastroesophageal reflux in symptomatic patients.

BACKGROUND: Recumbency and bending are thought to provoke symptoms of reflux in patients with gastroesophageal reflux disease (GERD). The effect of exercise which involved bending and abdominal contractions was evaluated in symptomatic patients of GERD using continuous 24-hour ambulatory esophageal pH test. METHODS: Twenty-five patients with GERD, confirmed by abnormal 24-hour esophageal pH study, performed exercise for 30 minutes consisting of 5 sessions of 6 minutes each. The exercise involved toe touching from supine, sitting and standing position of 2 minutes' duration each. Each 2 minutes' period included 8 repetitions of the same exercise of 15 seconds' duration. 24-hour esophageal pHmetry was done on day 1 without exercise and on day 2 with 30-minute exercise. Reflux time percent (RT%) pH <4 was compared between days 1 and 2 and 30 minutes before and during exercise. RESULTS: Fourteen patients were upright refluxers and 11 patients were combined refluxers, which included 4 patients with supine reflux and 7 patients who refluxed both in supine and upright positions. The median (range) 24-hour RT% on day 1 and day 2 was 7 (5-40) and 7 (4-46), respectively (p=0.15). RT% during 30 minutes exercise compared with 30 minutes before exercise was 6.6 (0-60) and 0.0 (0.0-80) (p=0.02), respectively. In combined and upright refluxers, RT% during and before exercise was 13 (0-53) and 0.0 (0.0-42) (p=0.008), respectively and 0.0 (0-60) and 0.0 (0-80), (p=0.71), respectively. RT% between upright and combined refluxers during exercise was 0.0 (0-60) and 13 (0-53), respectively (p=0.004). The mean (SD) LES pressure in mmHg in combined and upright refluxers was 7 (2.9) and 19.6 (6.8), respectively (p=0.008). Esophagitis in combined and upright refluxers was seen in 8 patients (72.7%) and 2 patients (14.3%), respectively. Two patients (8%) developed symptoms during exercise. CONCLUSION: Exercise which involves bending precipitates reflux in patients with moderate-to-severe GERD.

Pericardial effusion following esophageal variceal sclerotherapy.

We report a 37-year-old man with portal cavernoma who developed pericardial effusion two weeks following sclerotherapy for esophageal varices. It responded to conservative management.

Omeprazole as adjuvant therapy to endoscopic combination injection sclerotherapy for treating bleeding peptic ulcer.

BACKGROUND: Therapeutic endoscopy has provided a new means of treating bleeding peptic ulcers. Additional medical therapy may enhance the therapeutic benefit. Hemostasis is highly pH dependent and is severely impaired at low pH. Proton pump inhibitors, by achieving a significantly higher inhibition of gastric acidity, may improve the therapeutic outcomes after endoscopic treatment of ulcers. PATIENT AND METHODS: We enrolled 166 patients with hemorrhage from duodenal, gastric, or stomal ulcers and signs of recent hemorrhage, as confirmed by endoscopy. Twenty-six patients had ulcers with an arterial spurt, 41 patients had active ooze, 37 had a visible vessel, and 62 patients had an adherent clot. All patients received endoscopic injection sclerotherapy using 1:10,000 adrenaline and 1% polidocanol and were randomly assigned to receive omeprazole (40 mg orally) every 12 hours for 5 days or an identical-looking placebo. The outcome measures used were recurrent bleeding, surgery, blood transfusion, and hospital stay. RESULTS: Six (7%) of 82 patients in the omeprazole group had recurrent bleeding, as compared with 18 (21%) in the placebo group (P = 0.02). Two patients in the omeprazole group and 7 patients in the placebo group needed surgery to control their bleeding (P = 0.17). One patient in the omeprazole group and 2 patients in the placebo group died (P = 0.98). Twenty-nine patients (35%) in the omeprazole group and 61 patients (73%) in the placebo group received blood transfusions (P <0.001). The average hospital stay was 4.6 +/- 1.1 days in the omeprazole group and 6.0 +/- 0.7 days in the placebo group (P <0.001). CONCLUSION: The addition of oral omeprazole to combination injection sclerotherapy decreases the rate of recurrent bleeding, reduces the need for surgery and transfusion, and shortens the hospital stay for patients with stigmata of recent hemorrhage.

Gallbladder ascariasis: presentation and management.

BACKGROUND: As many as 1.5 billion people around the world harbour Ascaris lumbricoides in the digestive tract. Gallbladder ascariasis, although less common than bile duct ascariasis, is quite often seen in endemic areas. METHODS: Some 1300 patients with hepatobiliary ascariasis, admitted between October 1992 and June 1998, were analysed prospectively. The clinical features and outcome of 56 cases of gallbladder ascariasis are presented. RESULTS: Forty-seven patients were diagnosed by ultrasonography and nine were diagnosed at laparotomy. Only ten patients diagnosed by ultrasonography expelled the worms spontaneously, with resolution of symptoms and signs. The remaining 37 patients underwent cholecystectomy. CONCLUSION: Gallbladder ascariasis is a significant entity in endemic areas which usually requires cholecystectomy.

Percutaneous sonography-guided fine needle aspiration biopsy of colonoscopic biopsy-negative colonic lesions.

BACKGROUND: Pre-operative tissue diagnosis with colonoscopy is not always possible in patients with colonic lesions. OBJECTIVE: To study the usefulness and efficacy of percutaneous ultrasound-guided aspiration biopsy of colonic lesions. METHODS: Fifty consecutive patients with colonic lesions in whom colonoscopic brush cytology and biopsy were either negative or the lesion was not accessible on colonoscopy on two attempts, underwent percutaneous ultrasound-guided fine-needle aspiration biopsy. The results were compared with surgical findings. RESULTS: Fine-needle aspiration biopsy revealed adenocarcinoma in 40 patients; one had lymphoma, 2 had tuberculosis, 2 had abscess and 5 patients had negative aspiration. Forty-eight patients (excluding 2 with tuberculosis) underwent laparotomy and the diagnoses on aspiration biopsy were confirmed. Of the 5 negative aspirations, 3 had adenocarcinoma, one had tuberculosis and one intussusception. Thus, we had sensitivity of 91.8%, specificity of 100%, predictive value of positive results 100%, predictive value of negative results 20%, and percentage of false negative results 8.1%. Two patients developed complications--hemorrhage into the peritoneum and sepsis due to perforation at the site of aspiration; both survived after surgery. CONCLUSION: Percutaneous ultrasound-guided aspiration biopsy may be attempted for diagnosis of colonic lesions in situations where it may be the only means of obtaining a cytological diagnosis before surgery.

Ascaris-induced liver abscess.

The prevalence, symptomatology, and outcome of Ascaris-induced liver abscess was studied prospectively in Kashmir, India, which is an endemic area of ascariasis, from December 1987 to December 1997. Of 510 patients with liver abscess admitted during this period, 74 had biliary ascariasis as the cause (14.51%). Of these 74 patients, 11 had intact ascaridae (live or dead) within the abscess. Six patients had a single abscess, and five had multiple abscesses. Seven patients had associated worms in the bile ducts. Ultrasonography was the main diagnostic procedure used. Ten patients were diagnosed based on clinical and ultrasound findings, and one was diagnosed during laparotomy. Most of the patients were young (age range 3-40 years) with a mean age of 17.20 years. Seven were females, and four were males. Ten patients underwent surgery; nine recovered completely, and one died postoperatively due to septicemia. Another patient died as well: a young child who presented late, was in refractory septic shock following suppurative cholangitis and liver abscess, and could not be taken for surgery. The mortality thus was 9.9%. Liver abscess following invasion of intrahepatic biliary radicles by ascaridae through the ampulla is an unusual complication of an otherwise common disease in Kashmir Valley, affecting children and young adults. The outcome depends on early diagnosis and surgical drainage of the abscess with extraction of worms from the ducts.

Role of pulse oximetry during nonsedated upper gastrointestinal endoscopic procedures.

BACKGROUND: Although upper gastrointestinal endoscopy is generally a safe procedure, it is known to be associated with arterial oxygen desaturation, resulting in rare serious cardio-pulmonary events. OBJECTIVE: To determine the severity of oxygen desaturation during nonsedated upper gastrointestinal endoscopy and study the effect of various variables on oxygen saturation. METHODS: 126 patients underwent nonsedated upper gastrointestinal endoscopy (82 diagnostic, 44 therapeutic). Arterial oxygen saturation (SaO2) was monitored using a pulse oximeter. RESULTS: Baseline SaO2 was mean (SD) 97.8 (1.8%). It remained > 95% in 60.2% of patients during the procedure, whereas mild oxygen desaturation (SaO2 90%-94%) occurred in 23.7% and severe oxygen desaturation (SaO2 < 90%) occurred in 15.8% of patients. Six patients (4.7%) required supplemental oxygen administration sometime during the procedure. Desaturation occurred in patients undergoing diagnostic and therapeutic procedures but was severe in the latter group (p < 0.002). Patients aged more than 60 years (p < 0.001), hemoglobin < 10 g/dL (p < 0.001), history of smoking (p < 0.001), and underlying chronic obstructive airway disease (p < 0.001) were significantly related to oxygen desaturation. However, on multivariate analysis, no significant correlation was observed with hemoglobin value. CONCLUSION: Therapeutic intervention during nonsedated upper gastrointestinal endoscopy, old age, smokers and chronic obstructive airways disease are independent risk factors for oxygen desaturation. We recommend continuous monitoring of SaO2 in these high-risk patients undergoing upper gastrointestinal endoscopy.

Short-course ceftriaxone therapy in spontaneous bacterial peritonitis.

Forty patients with spontaneous bacterial peritonitis, three of whom had complicating acute hepatitis syndrome, eight late-onset hepatic failure, and 29 with cirrhosis, were treated with ceftriaxone 2 g intravenously once daily for 5 days. Ascitic fluid culture was positive in 28 patients, with Escherichia coli and Klebsiella as common isolates. All the bacteria isolated were sensitive to ceftriaxone except Enterococcus faecalis, which was isolated in a cirrhotic patient. All culture-positive patients sensitive to ceftriaxone showed bacteriological cure and 26 (65%) patients showed cytological cure after 48 hours of treatment. A total of 95% were cured of their infection after 5 days of treatment. Twelve (30%) patients died during hospitalisation after documented cure of their spontaneous bacterial peritonitis (renal failure, gastrointestinal bleed and cerebral oedema were the primary causes of death). Infection-related mortality due to Pseudomonas septicaemia was seen in one cirrhotic patient.

A comparison of omeprazole and placebo for bleeding peptic ulcer.

BACKGROUND: The role of medical treatment for patients with bleeding peptic ulcers is uncertain. METHODS: We conducted a double-blind, placebo-controlled trial in 220 patients with duodenal, gastric, or stomal ulcers and signs of recent bleeding, as confirmed by endoscopy. In 26 patients the ulcers showed arterial spurting, in 34 there was active oozing, in 35 there were nonbleeding, visible vessels, and in 125 there were adherent clots. The patients were randomly assigned to receive omeprazole (40 mg given orally every 12 hours for five days) or placebo. The outcome measures studied were further bleeding, surgery, and death. RESULTS: Twelve of the 110 patients treated with omeprazole (10.9 percent) had continued bleeding or further bleeding, as compared with 40 of the 110 patients who received placebo (36.4 percent) (P<0.001). Eight patients in the omeprazole group and 26 in the placebo group required surgery to control their bleeding (P<0.001). Two patients in the omeprazole group and six in the placebo group died. Thirty-two patients in the omeprazole group (29.1 percent) and 78 in the placebo group (70.9 percent) received transfusions (P<0.001). A subgroup analysis showed that omeprazole was associated with significant reductions in recurrent bleeding and surgery in patients with nonbleeding, visible vessels or adherent clots, but not in those with arterial spurting or oozing. CONCLUSIONS: In patients with bleeding peptic ulcers and signs of recent bleeding, treatment with omeprazole decreases the rate of further bleeding and the need for surgery.