Argon plasma coagulation is an effective treatment for chronic radiation proctitis in gynaecological malignancy: an observational study.

AIM: Chronic radiation proctitis (CRP) develops in 5-15% of patients after pelvic radiation therapy, with rectal bleeding being the main symptom. Reports suggest that argon plasma coagulation (APC) can be an effective therapy for CRP following radiotherapy for prostate cancer, but there is less information about how useful it is after radiotherapy for gynaecological malignancy. The aim of this work therefore was to study the efficacy of APC for CRP after radiotherapy for gynaecological malignancy. METHOD: This was a prospective study of consecutive patients with CRP following radiotherapy for gynaecological malignancy at IPGME&R, SDLD, Kolkata, India; symptoms included rectal bleeding grade (RBG) ≥ 2. APC was performed at monthly intervals to a maximum of four treatment sessions. Severity of disease at baseline was graded (endoscopically) by the total colonoscopic severity score (TCSS) and treatment response was assessed by reduction in RBG from ≥ 2 to ≤ 1 measured at > 6 months after cessation of APC. RESULTS: Seventy patients [90% with cervical cancer, 10% with endometrial cancer; mean age 51.93 ± 9.15 years; median RBG 3 (range 2-4)] received APC. Seven patients died due to underlying malignancy and seven patients were lost to follow-up. Fifty-six (85.7%) patients responded to therapy after a median of 2 (range 1-4) treatment sessions. Multivariate analysis demonstrated that a lower haemoglobin at the start of treatment predicted failure of therapy (P < 0.05). CONCLUSION: APC is an effective management option for CRP in female patients with gynaecological malignancy. However, the more anaemic the patient the less likely it is to be successful.

Natural resolution or intervention for fluid collections in acute severe pancreatitis.

BACKGROUND: Revisions in terminology of fluid collections in acute pancreatitis have necessitated reanalysis of their evolution and outcome. The course of fluid collections in patients with acute pancreatitis was evaluated prospectively. METHODS: Consecutive adults with acute pancreatitis, who had contrast-enhanced CT (CECT) within 5-7 days of symptom onset, were enrolled in a prospective cohort study in a tertiary-care centre. Patients were treated according to standard guidelines. Follow-up transabdominal ultrasonography was done at 4-week intervals for at least 6 months. CECT was repeated at 6-10 weeks, or at any time if there were new or persistent symptoms. Asymptomatic collections were followed until spontaneous resolution. Risk factors for pancreatic pseudocysts or walled-off necrosis (WON) were assessed in multivariable analyses. RESULTS: Of 122 patients with acute pancreatitis, 109 were analysed. Some 91 patients (83·5 per cent) had fluid collections at baseline. Eleven of 29 with interstitial oedematous pancreatitis had acute peripancreatic fluid collections, none of which evolved into pseudocysts. All 80 patients with acute necrotizing pancreatitis had at least one acute necrotizing collection (ANC); of these, five patients died (2 after drainage), three underwent successful drainage within 5 weeks, and collections resolved spontaneously in 33 and evolved into WON in 39. By 6 months' follow-up, WON had required drainage in eight patients, resolved spontaneously in 23 and was persistent but asymptomatic in seven. Factors associated with increased risk of WON were blood urea nitrogen 20 mg/dl or more (odds ratio (OR) 10·96, 95 per cent c.i. 2·57 to 46·73; P = 0·001) and baseline ANC diameter greater than 6 cm (OR 14·57, 1·60 to 132·35; P = 0·017). Baseline ANC diameter over 6 cm was the only independent predictor of either the need for drainage or persistence of such collections beyond 6 months (hazard ratio 6·61, 1·77 to 24·59; P = 0·005). CONCLUSION: Pancreatic pseudocysts develop infrequently in oedematous acute pancreatitis. Only one-quarter of ANCs either require intervention or persist beyond 6 months, whereas more than one-half of WONs resolve without any intervention within 6 months of onset. Baseline diameter of ANC(s) is an important predictor of outcome.

External validation of Chronic Pancreatitis Prognosis Score (COPPS): A prospective cohort study.

BACKGROUND: Prognostic stratification in ChronicPancreatitis(CP) remains suboptimal and cumbersome. Chronic Pancreatitis Prognostic Score(COPPS) was recently developed to predict one-year hospitalisations in CP. AIM: External validation of COPPS in a geographically divergent patient population. METHODS: A single-center prospective cohort study, conducted on out-patients of a tertiary-care hospital. Consecutive adults with CP were assessed for COPPS risk predictors at baseline, similar to the original development cohort, and followed for one-year for: 1)hospitalisations; 2)development of pancreatitis-related complications; and 3)need for endoscopic and/or surgical interventions. Outcomes were compared by Kendall's tau-b(τb) and other statistical tests. Only those who had complete one-year follow-up were included in analysis. RESULTS: There were 177 patients(mean±SD age: 35.9 ± 11.2 years), 116(65%) males and 117(66%) with Idiopathic CP. Despite being younger, with significantly more females and Idiopathic CP, than the original development cohort, our cohort was similar to the latter regarding COPPS severity at baseline. Eight patients died over one-year; 169 were evaluated for outcomes. Increasingly severe COPPS categories correlated with increasing number of hospitalisations(both overall and pancreatitis-related) and increasing number of days spent in hospital(both overall and pancreatitis-related) irrespective of age at symptoms-onset(≤35 vs >35years), etiology(idiopathic vs alcohol) and smoking-status. CONCLUSIONS: COPPS is effective in a geographically distinct cohort having a different case-mix of CP patients(ClincialTrials.gov ID:NCT04907266).

Indian guidelines on imaging of the small intestine in Crohn's disease: A joint Indian Society of Gastroenterology and Indian Radiology and Imaging Association consensus statement.

The Indian Society of Gastroenterology (ISG) Task Force on Inflammatory Bowel Disease and the Indian Radiological and Imaging Association (IRIA) developed combined ISG-IRIA evidence-based best-practice guidelines for imaging of the small intestine in patients suspected to have or having Crohn's disease. The 29 consensus statements, developed through a modified Delphi process, are intended to serve as reference for teaching, clinical practice, and research.

Imaging of the small intestine in Crohn's disease: Joint position statement of the Indian Society of Gastroenterology and Indian Radiological and Imaging Association.

The Indian Society of Gastroenterology (ISG) Task Force on Inflammatory Bowel Disease and the Indian Radiological and Imaging Association (IRIA) developed combined ISG-IRIA evidence-based best-practice guidelines for imaging of the small intestine in patients with suspected or known Crohn's disease. These 29 position statements, developed through a modified Delphi process, are intended to serve as reference for teaching, clinical practice, and research.

Extraintestinal manifestations in inflammatory bowel disease: Prevalence and predictors in Indian patients.

BACKGROUND: There is a paucity of reports on extraintestinal manifestations (EIMs) in patients with inflammatory bowel diseases (IBD) from Asia and India. METHODS: From May 2011 to October 2012, consecutive IBD patients underwent a detailed history and physical examination, also by trained rheumatologist, dermatologist, and ophthalmologist, about whether they experienced any EIM at the time of inclusion or in the past. The disease phenotype/severity and location was classified according to the Montréal classification. All underwent magnetic resonance imaging (MRI) of sacroiliac joints, liver function test (LFT), transabdominal ultrasound, and dual energy X-ray absorptiometry (DEXA) scanning at neck femur (bilateral) and L4-L5 spine. RESULTS: One hundred twenty patients were analyzed, 62 had Crohn's disease (CD) and 58 had ulcerative colitis (UC). Thirty-eight percent had at least one while 20% suffered from multiple EIMs. Except for uveitis and episcleritis, the frequency of individual EIMs did not differ between CD and UC patients. Twenty-three percent had peripheral arthritis, 18% had ankylosing spondylitis, and 13% had ophthalmological manifestations. Mucocutaneous manifestations, aphthous stomatitis and pyoderma gangrenosum (PG), were seen in 9%. None had erythema nodosum (EN) or primary sclerosing cholangitis (PSC). Fifty percent of patients had either osteopenia or osteoporosis on DEXA. Multivariable analysis revealed female gender, Hindu religion, severe disease, and steroid usage were significantly associated with the presence of EIMs. CONCLUSION: The prevalence of EIM is similar to that reported from Europe and USA, albeit higher than that previously reported in Asian patients. Female sex, religion, severe disease, and steroid use were associated with EIM.

ERCP in situs inversus: do we need to turn the other way?

Endoscopic procedures are difficult in patients with situs inversus owing to left-right reversal of viscera. Conventionally, reversal of the position of the endoscopist in relation to the patient is advocated to overcome the anatomical difficulty. We describe a patient with chronic calcific pancreatitis and pseudocyst of the pancreas who had situs inversus. ERCP was performed with minor modification of maneuvers with the patient in the usual left lateral decubitus and the endoscopist on the left of the table.

Induction of oxidative stress in antitubercular drug-induced hepatotoxicity.

BACKGROUND AND AIM: Oxidative stress could play a role in the pathogenesis of antitubercular drug (ATD)-induced hepatotoxicity. We therefore studied the plasma level of reduced glutathione (GSH) and malondialdehyde (MDA) in patients with ATD-induced hepatotoxicity (cases), ATD-treated controls (disease controls) and in healthy volunteers. METHODS: This study was carried out in a case-control design. Twenty-one cases, 21 age- and sex-matched disease controls, and 10 healthy volunteers were enrolled. Plasma levels of GSH and MDA were measured. RESULTS: Plasma levels of GSH (median [range] 11.5 [6.2-21.2] mmol/dL) and MDA (1390 [560-2310] nmol/dL) of cases were significantly different (p<0.01) from GSH (18.4 [10.5-24.4]) and MDA (290 [240-550]) of disease controls. Further, plasma GSH and MDA levels of both the ATD-treated groups were different from those in healthy controls. CONCLUSION: Lower levels of plasma GSH and higher levels of MDA may be due to oxidative stress resulting from ATD therapy.

Treatment of chronic anal fissure with topical glyceryl trinitrate: a double-blind, placebo-controlled trial.

BACKGROUND: Topical glyceryl trinitrate (GTN) may produce healing of anal fissure by decreasing the high resting anal sphincter pressure in these patients. The present study assessed the efficacy of GTN in chronic anal fissure in a double-blind placebo-controlled trial. METHOD: Patients with chronic anal fissure (for more than 8 weeks) underwent measurement of maximum anal resting pressure (MARP) before and 12 minutes after application of either 0.2% GTN or placebo ointment in a randomized manner. They then received twice-daily local application of their respective ointment for 6 weeks. Symptoms and healing of fissure were assessed; patients were evaluated at 3 months for evidence of relapse. RESULTS: 19 adult patients (12 men) were studied; 10 received GTN and 9 placebo. Mean (SD) MARP decreased from 131.0 (32.3) cm H2O to 93.5 (28.4) cm H2O (p<0.05) with GTN and from 150.5 (36.9) cm H2O to 142.8 (35.0) cm H2O (p=ns) with placebo. Fissure healed in 7 of 10 patients treated with GTN and 2 of 9 patients treated with placebo (p<0.05). There was no relapse of fissure in either group. CONCLUSION: Local application of GTN was effective in healing chronic anal fissure.

Patient-posture and Ileal-intubation during colonoscopy (PIC): a randomized controlled open-label trial.

BACKGROUND AND AIMS: Patient's posture change is commonly employed by a colonoscopist to achieve complete examination. We studied whether patient's posture (left-lateral decubitus vs supine) influenced the success rate of ileal intubation. PATIENTS AND METHODS: In this prospective open-label randomized study performed in the Endoscopy Suite of a tertiary-care center, all adult outpatients referred for colonoscopy, in whom cecal intubation was achieved and who satisfied predefined inclusion criteria, were randomized to undergo ileal intubation in either of the above two postures. Colonoscopy (EC-201 WL, Fujinon) was performed after overnight poly-ethylene-glycol preparation, under conscious sedation and continuous pulse-oxymetry monitoring. After confirming cecal intubation, patients were randomized for ileal intubation. Success was defined by visualization of ileal mucosa or villi (confirmed by digital photography) and was attempted until limited by pain and/or time of ≥ 6 min. RESULTS: Of 320 eligible patients, 217 patients (150 males) were randomized, 106 to left-lateral decubitus and 111 to supine posture. At baseline, the two groups were evenly matched. Successful ileal intubation was achieved in 145 (66.8 %) patients overall, significantly higher in the supine posture (74.8 % versus 58.5 %; P = 0.014). On multivariate analysis, supine posture (P = 0.02), average/good right-colon preparation (P < 0.01), non-thin-lipped ileocecal (IC) valve (P < 0.001) and younger age (P = 0.02) were independent predictors of success. Positive ileal findings were recorded in 13 (9 %) patients. CONCLUSION: Ileoscopy is more successful in supine than in left-lateral decubitus posture. Age, bowel preparation and type of IC valve also determine success.

IL1B induced Smad 7 negatively regulates gastrin expression.

BACKGROUND: Helicobacter pylori elicited IL1B is one of the various modulators responsible for perturbation of acid secretion in gut. We have earlier reported that IL1B activated NFkB downregulates gastrin, a major modulator of acid secretion. However, we hypothesized that regulation of gastrin by IL1B would depend on the cell's ability to integrate inputs from multiple signaling pathways to generate appropriate biological response. PRINCIPAL FINDING: In this study, we report that IL1B induces Smad 7 expression by about 4.5 fold in gastric carcinoma cell line, AGS. Smad 7 resulted in transcriptional repression of gastrin promoter by about 6.5 fold when co-transfected with Smad 7 expression vector and gastrin-promoter luciferase in AGS cells. IL1B inhibited phosphorylation of Smad 3 and subsequently interfered with nuclear translocation of the positive Smad complex, thus occluding it off the gastrin promoter. IL1B promoter polymorphisms (-511T/-31C IL1B) are known to be associated with H. pylori associated gastro-duodenal ulcer. We observed that IL1B expressed from -31T promoter driven IL1B cDNA elicited 3.5 fold more Smad 7 than that expressed from the IL1B-31C variant in AGS cells. This differential activation of Smad 7 by IL1B promoter variants translated into differential downregulation of gastrin expression. We further analyzed Smad 7, NFkB, IL1B and gastrin expression in antral gut biopsy samples of patients with H. pylori associated duodenal ulcer and normal individuals. We observed that individuals with duodenal ulcer had significantly lower levels of IL1B, Smad 7, NFkB and corresponding higher level of gastrin expression. CONCLUSION: Pro-inflammatory cytokine IL1B repress gastrin expression by activating Smad 7 and subsequent inhibition of nuclear localization of Smad 3/4 complex. Polymorphic promoter variants of IL1B gene can modulate the IL1B expression which resulted in differential activation Smad 7 and consequent repression of gastrin expression, respectively. Analysis of H. pylori infected duodenal ulcer patient's gut biopsy samples also supported this observation.

Epidemiology and symptom profile of gastroesophageal reflux in the Indian population: report of the Indian Society of Gastroenterology Task Force.

BACKGROUND: Gastroesophageal reflux disease (GERD) and its complications are thought to be infrequent in India; there are no data from India on the prevalence of and risk factors for GERD. The Indian Society of Gastroenterology formed a task force aiming to study: (a) the frequency and profile of GERD in India, (b) factors including diet associated with GERD. METHODS: In this prospective, multi-center (12 centers) study, data were obtained using a questionnaire from 3224 subjects regarding the frequency, severity and duration of heartburn, regurgitation and other symptoms of GERD. Data were also obtained regarding their dietary habits, addictions, and lifestyle, and whether any of these were related or had been altered because of symptoms. Data were analyzed using univariate and multivariate methods. RESULTS: Two hundred and forty-five (7.6%) of 3224 subjects had heartburn and/or regurgitation at least once a week. On univariate analysis, older age (OR 1.012; 95% CI 1.003-1.021), consumption of non-vegetarian and fried foods, aerated drinks, tea/coffee were associated with GERD. Frequency of smoking was similar among subjects with or without GERD. Body mass index (BMI) was similar in subjects with and without GERD. On multivariate analysis, consumption of non-vegetarian food was independently associated with GERD symptoms. Overlap with symptoms of irritable bowel syndrome was not uncommon; 21% reported difficulty in passage of stool and 9% had mucus in stools. About 25% of patients had consulted a doctor previously for their gastrointestinal symptoms. CONCLUSION: 7.6% of Indian subjects have significant GERD symptoms. Consumption of non-vegetarian foods was an independent predictor of GERD. BMI was comparable among subjects with or without GERD.

Role of anti-Helicobacter pylori treatment in H. pylori-positive and cytoprotective drugs in H. pylori-negative, non-ulcer dyspepsia: results of a randomized, double-blind, controlled trial in Asian Indians.

BACKGROUND: The efficacy of anti-Helicobacter pylori treatment and cytoprotective drugs in H. pylori-positive and -negative non-ulcer dyspepsia (NUD), respectively, is debatable. METHODS: In a randomized study, the efficacy of anti-H. pylori treatment versus sucralphate was tested in patients with NUD. One hundred and twelve patients with NUD, 62 positive and 50 negative for H. pylori were studied. Of 62 patients positive for H. pylori, 32 were treated with triple therapy (colloidal bismuth subcitrate, tetracycline and metronidazole) for 2 weeks and the remaining 30 were treated with sucralphate (1 g, q.i.d.) for 4 weeks. Of 50 patients negative for H. pylori, 25 each were treated with either sucralphate (1 g, q.i.d.) or ranitidine (150 mg, b.d.) for 4 weeks. RESULTS: In patients with NUD and H. pylori infection, triple therapy eradicated H. pylori in 88% and was superior to sucralphate in producing symptom relief (81 vs 33%, P = 0.0003) and histological improvement in gastritis (73 vs 30%, P = 0.003). In the H. pylori-negative group, sucralphate was superior to ranitidine with regard to symptom relief (68 vs 36%, P = 0.04) and improvement in gastritis (44 vs 12%, P = 0.09). The symptomatic improvement persisted until 12 weeks after the start of treatment in triple therapy group only. CONCLUSIONS: In patients with NUD associated with H. pylori, triple therapy was better than sucralphate in terms of symptomatic and histological improvement. However, sucralphate was superior to ranitidine in providing symptom relief in patients with H. pylori-negative NUD.

Microscopic colitis is a cause of large bowel diarrhea in Northern India.

Chronic diarrhea is a common clinical problem. To determine the possible causes in North India, we studied prospectively 71 patients with chronic diarrhea of the large bowel type. A definite diagnosis could be established in 70 patients. Ulcerative colitis was found in 18 patients, colorectal malignancies in three, colonic polyps in three, and irritable bowel syndrome in 32. In addition, seven patients with seronegative polyarthritis and chronic diarrhea were found to have chronic inflammation of the colon on histology. Two patients had pseudodiarrhea, and no diagnosis could be established in one patient. The remaining five patients with chronic diarrhea showed histologic evidence of chronic colonic inflammation with predominantly mononuclear cell infiltration of the lamina propria and increased intraepithelial lymphocytes, but results of their radiologic and endoscopic studies were normal. These five patients were classified as having microscopic (lymphocytic) colitis. We conclude that the causes of chronic diarrhea in North India patients are similar to a large extent to those seen in Western populations. Microscopic (lymphocytic) colitis is a definite clinicopathologic entity that should be considered in the differential diagnosis of chronic diarrhea.

Role of infectious agents in exacerbations of ulcerative colitis in India. A study of Clostridium difficile.

Fifty patients with idiopathic ulcerative colitis--25 with acute exacerbation of the disease (Group I) and 25 in quiescent phase (Group II)--were studied. None of the patients had a history of recent exposure to antimicrobial drugs or hospitalization. Evidence of infection with protozoal and bacterial agents and/or presence of Clostridium difficile toxin was demonstrated in eight (32%) patients in group I and one (4%) patient in group II (group I vs. group II, p < 0.05; chi 2 test with Yate's correction). In five of the six patients with demonstrable Clostridium difficile toxin in the stool, one patient with Entamoeba trophozoites, and another with Salmonella infection, the exacerbation responded clinically and endoscopically to specific antimicrobial therapy. Another two patients who had Entamoeba histolytica cysts in the stool had no change in their clinical status with metronidazole. We conclude that infectious agents are responsible for some of the exacerbations in patients of ulcerative colitis in a tropical country like India, where careful microbiologic examination is in order in every acute exacerbation of this disease. This contrasts with the findings in developed countries.

Multiplex PCR assay for rapid detection and genotyping of Helicobacter pylori directly from biopsy specimens.

We developed and evaluated a simple, novel multiplex PCR assay for rapid detection of Helicobacter pylori infection and for the determination of vacA and cagA genotypes directly from gastric biopsy specimens. This assay did not require culturing of strains or extraction of DNA from biopsy samples. This multiplex PCR assay would be of particularly great value for laboratories in developing countries.