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BACKGROUND The incidence of colorectal cancer is rising in several developing countries. In the absence of integrated endoscopy and pathology databases, adenoma detection rate (ADR), as a validated quality indicator of screening colonoscopy, is generally difficult to obtain in practice. We aimed to measure the correlation of polyp-related indicators with ADR in order to identify the most accurate surrogate(s) of ADR in routine practice. METHODS We retrospectively reviewed the endoscopic and histopathological findings of patients who underwent colonoscopy at a tertiary gastrointestinal clinic. The overall ADR and advanced-ADR were calculated using patient-level data. The Pearson's correlation coefficient (r) was applied to measure the strength of the correlation between the quality metrics obtained by endoscopists. RESULTS A total of 713 asymptomatic adults aged 50 and older who underwent their first-time screening colonoscopy were included in this study. The ADR and advanced-ADR were 33.00% (95% CI: 29.52-36.54) and 13.18% (95% CI: 10.79-15.90), respectively. We observed good correlations between polyp detection rate (PDR) and ADR (r=0.93), and mean number of polyp per patient (MPP) and ADR (r=0.88) throughout the colon. There was a positive, yet insignificant correlation between advanced ADRs and non-advanced ADRs (r=0.42, p=0.35). CONCLUSION MPP is strongly correlated with ADR, and can be considered as a reliable and readily obtainable proxy for ADR in opportunistic screening colonoscopy programs.

Observational studies revealed a relationship between changes in gastric mucosa and risk of esophageal squamous cell carcinoma (ESCC) which suggested a possible role for gastric microbiota in ESCC carcinogenesis. In this study we aimed to compare pattern of gastric corpus microbiota in ESCC with normal esophagus. Cases were included subjects with early ESCC (stage I-II) and esophageal squamous dysplasia (ESD) as the cancer precursor. Control groups included age and sex-matched subjects with mid-esophagus esophagitis (diseased-control), and histologically normal esophagus (healthy-control). DNA was extracted from snap-frozen gastric corpus tissues and 16S rRNA was sequenced on GS-FLX Titanium. After noise removal, an average of 3004 reads per sample was obtained from 93 subjects. We applied principal coordinate analysis to ordinate distances from beta diversity data. Pattern of gastric microbiota using Unifrac (p = 0.004) and weighted Unifrac distances (p = 0.018) statistically varied between cases and healthy controls. Sequences were aligned to SILVA database and Clostridiales and Erysipelotrichales orders were more abundant among cases after controling for multiple testing (p = 0.011). No such difference was observed between mid-esophagitis and healthy controls. This study is the first to show that composition of gastric corpus mucosal microbiota differs in early ESCC and ESD from healthy esophagus.

Background: Data on the quality of colonoscopies in populations with rising colorectal cancer (CRC) incidence is scarce. We aimed to calculate the adenoma detection rates (ADR), and assess the quality of colonoscopies in an opportunistic screening colonoscopy program in Iran., Methods: All the colonoscopy and pathology reports of asymptomatic adults over age 50 who underwent screening colonoscopy between June 2007 and March 2013 were reviewed. The colonoscopy quality indicators including ADR were calculated, and patient factors associated with the adenoma detection were determined., Results: A total of 713 asymptomatic adults aged 50 years and older who underwent their first-time screening colonoscopy were included in this study. ADR and advanced-ADR were 33.00% (95% CI: 29.52-36.54) and 13.18% (95% CI: 10.79-15.90), respectively. We observed a significantly higher rate of cecal intubation in patients with fair or better bowel preparation compared to those with poor prep, 90.00% vs. 70.45%, respectively (P < 0.001). Bowel preparation (adjusted OR: 2.49, 95% CI: 1.75-3.55), older age (≥60) (adjusted OR: 1.70, 95% CI: 1.22-2.36), and male gender (adjusted OR: 1.39, 95% CI: 1.01-1.92) were associated with the adenoma detection., Conclusions: Our ADR in both genders meets and exceeds the recommended colonoscopy quality benchmarks. The polyp and adenoma detection rates in the current study are comparable to those reported from Western countries where the incidence of CRC is traditionally high. These data are in line with the epidemiologic transition of CRC in Iran.

BACKGROUND Early diagnosis and endoscopic resection of adenomatous polyps is the main approach for screening and prevention of colorectal cancer (CRC). We aimed to assess polyp detection rate (PDR) and to characterize demographic, clinical, and pathological features of colorectal polyps in an Iranian population. METHODS We retrospectively analyzed the data from 5427 colonoscopies performed during 2007-2012 at Masoud Clinic, the main endoscopy center associated with Sasan Alborz Biomedical Research Center, in Tehran, Iran. RESULTS Our sample included 2928 (54%) women and 2499 (46%) men, with the mean age of 48.3 years (SD=16.1). The most common reasons for colonoscopy included screening in 25.0%, and gastrointestinal bleeding in 15.2%. Cecal intubation was successful in 86% of patients. The quality of bowel preparation was fair to excellent in 78.1% (n=4235) of colonoscopies. Overall PDR was 42.0% (95% CI: 40.6-43.3). The PDR in men (51.1%, 95% CI: 49.1-53.1) was significantly higher than women (34.2%, 95% CI: 32.4-35.9, p<0.001). Polyps were more frequently observed in patients after the 6(th) decade of life (F=3.2; p=0.004). CRC was detected in 2.9% (73/2499) of men and 1.9% (57/2928) of women (p=0.02). The mean age for patients with cancer was significantly higher than that for individuals with polyps, 60.9 (SD=13.4) year vs. 56.9 (SD=13.7) year, respectively (p=0.001). Almost 82.8% of the lesions were precancerous with tubular type predominance (62.3%) followed by tubulo-villous (10.3%), villous (6.6%), and serrated (3.6%). Hyperplastic/inflammatory polyps comprised 17.2% of lesions. CONCLUSION Distal colon was more prone to develop polyps and cancer than proximal colon in our series. These findings provide a great infrastructure for next preventive programs and have implications for colorectal cancer screening at population-level.

BACKGROUND Only a few studies in Western countries have investigated the association between gastroesophageal reflux disease (GERD) and mortality at the general population level and they have shown mixed results. This study investigated the association between GERD symptoms and overall and cause-specific mortality in a large prospective population-based study in Golestan Province, Iran. METHODS Baseline data on frequency, onset time, and patient-perceived severity of GERD symptoms were available for 50001 participants in the Golestan Cohort Study (GCS). We identified 3107 deaths (including 1146 circulatory and 470 cancer-related) with an average follow-up of 6.4 years and calculated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for multiple potential confounders. RESULTS Severe daily symptoms (defined as symptoms interfering with daily work or causing nighttime awakenings on a daily bases, reported by 4.3% of participants) were associated with cancer mortality (HR 1.48, 95% CI: 1.04-2.05). This increase was too small to noticeably affect overall mortality. Mortality was not associated with onset time or frequency of GERD and was not increased with mild to moderate symptoms. CONCLUSION We have observed an association with GERD and increased cancer mortality in a small group of individuals that had severe symptoms. Most patients with mild to moderate GERD can be re-assured that their symptoms are not associated with increased mortality.

Background: Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time., Methods: We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼ 50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn., Results: Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02-1.75) and opium use (OR 1.70, 95% CI 1.55-1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76-0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined)., Conclusion: GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.

BACKGROUND NAFLD/NASH is a manifestation of metabolic syndrome and is associated with obesity/overweight. Not all obese/overweight individuals develop NASH. Gastro-esophageal reflux disease (GERD) is considered a gastrointestinal manifestation of the metabolic syndrome and is associated with obesity/overweight. Again not all obese/overweight individuals develop GERD. Recent data show association of dietary nitrate content and oral nitrate reductase activity (NRA) with GERD. Nitrates need to be converted to nitrite (done in human beings by nitrate reductase of oral bacteria exclusively) to be active in metabolic pathways. OBJECTIVE To assess the relation between NASH/NAFLD and oral NRA. METHODS Oral NRA was measured in individuals with NASH (compatible abdominal ultrasound and two elevated ALT/AST levels over six months) and was compared with that of those without NASH. Oral NRA was measured according to a previously reported protocol. RESULTS Eleven NASH patients and twelve controls were enrolled. Mean oral NRA activity were 2.82 vs. 3.51 μg nitrite-N formed per person per minute for cases and controls respectively (p=0.46). CONCLUSION According to our data, oral nitrite production is not different between individual swith and without NASH.

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes in the general population. NASH and to some extent NAFLD have been associated with increased liver-related and all-cause mortality. No effective treatment is yet available. Recent reports have shown that the use of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with elevated plasma aminotransferases may result in normalisation of these liver enzymes. Whether this is a consistent effect or whether it can lead to improved clinical outcomes beyond normalisation of abnormal liver enzymes is not clear., Objectives: To assess the beneficial and harmful effects of statins (that is, lovastatin, atorvastatin, simvastatin, pravastatin, rosuvastatin, and fluvastatin) on all-cause and liver-related mortality, adverse events, and histological, biochemical, and imaging responses in patients with NAFLD or NASH., Search Methods: We performed a computerised literature search in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded up to March 2013. We did fully recursive searches from the reference lists of all retrieved relevant publications to ensure a complete and comprehensive search of the published literature. We did not apply any restrictions regarding language of publication or publication date., Selection Criteria: All randomised clinical trials using statins as the primary treatment for NAFLD or NASH versus no treatment, placebo, or other hypolipidaemic agents., Data Collection and Analysis: Data were extracted, and risk of bias of each trial was assessed independently by two or more review authors. Meta-analyses were performed whenever possible. Review Manager 5.2 was used., Main Results: When the described search method was used and the eligibility criteria of the search results were applied, 653 records were found. Only two of these were randomised clinical trials that were considered eligible for inclusion. We assessed both trials as trials with high risk of bias. One of the trials was a pilot trial in which 16 participants with biopsy-proven NASH were randomised to receive simvastatin 40 mg (n = 10) or placebo (n = 6) once daily for 12 months. No statistically significant improvement in the aminotransferase level was seen in the simvastatin group compared with the placebo group. Liver histology was not significantly affected by simvastatin.The other trial had three arms. The trial compared atorvastatin 20 mg daily (n = 63) versus fenofibrate 200 mg daily (n = 62) versus a group treated with a combination of the two interventions (n = 61). There were no statistically significant differences between any of the three intervention groups regarding the week 54 mean activity levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The triglyceride levels seemed higher in the fenofibrate group compared with the atorvastatin group. Liver histology was not assessed in this trial. The presence of biochemical and ultrasonographic evidence of NAFLD seemed to be higher in the fenofibrate group compared with the atorvastatin group (58% versus 33%). Three patients discontinued treatment due to myalgia and elevated serum creatine kinase activity; one from the atorvastatin group and two from the combination group. Another patient from the atorvastatin group discontinued treatment due to alanine aminotransferase activity that was over three times the upper normal limit.No data for all-cause mortality and hepatic-related mortality were reported in the included trials., Authors' Conclusions: Based on the findings of this review, which included two trials with high risk of bias and a small numbers of participants, it seems possible that statins may improve serum aminotransferase levels as well as ultrasound findings. Neither of the trials reported on possible histological changes, liver-related morbidity or mortality. Trials with larger sample sizes and low risk of bias are necessary before we may suggest statins as an effective treatment for patients with NASH. However, as statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified.

Background: Corticosteroids are used to induce remission in auto-immune hepatitis.They are not universally effective; therefore, alternative treatments are needed.In this study Cysclosporine-A has been compared with prednisolone as an alternativetreatment in a randomized controlled trial. This paper is an interimanalysis of an ongoing clinical trial., Methods: Sixteen years and older consenting patients were enrolled. Group-A receivedprednisolone and group-B cyclosporine-A according to a preset protocoland followed at regular intervals for 48 weeks. Final assessment was doneat week 48. Primary outcome was response rate as defined below. "Completeresponse" was defined as achieving AST and ALT in the normal range andabsence of any clinical signs of deterioration, and partial response was definedas a decrease in AST and ALT by less than half of their original values but notto within normal limit. Non-responding ones at week eight were switched tothe other arm., Results: Thirty-nine patients were enrolled (24 group-A, 9 male). Mean AST andALT at baseline were higher in group-B, but other variables were comparable.At week 12, 34.8% and 64.3% of group-A and B had achieved AST and ALTin the normal range (less than 40 IU/L) respectively (p=0.081). Correspondingfigures at week 48 were 50.0% and 47.6% (p=0.62 & 0.48 respectively).At week 12, 86.9% and 85.7% of patients had AST and ALT levels less thantwice upper normal limit in groups-A and B respectively (p=0.54 & 0.42).Corresponding figures at week 48 were 90.0% for both groups. There was onetreatment failure in group-B which did not respond to prednisolone either.Serious adverse events (death and liver transplantation) occurred in group-Aonly. Serum creatinine did not change during the study period in either group., Conclusion: According to our data, Cyclosporine-A is as effective as prednisolone forinduction of remission in AIH. Adverse events and serious adverse events weremore common with prednisolone.

Background: Assessment of glomerular filtration rate (GFR) by common creatininebasedmethods is potentially inaccurate in patients with cirrhosis. Cirrhoticpatients have several underlying conditions that contribute to falsely low serumcreatinine concentrations, even in the presence of moderate to severe renalimpairment. Therefore creatinine-based methods usually overestimate trueGFR in these patients. Cystatin-C is a low molecular weight protein and anendogenous marker of GFR. We compared the accuracy of plasma cystatin-Cand creatinine in assessing renal function in cirrhotic patients., Methods: We serially enrolled cirrhotic patients with stable renal function admitted inour ward if they met the inclusion criteria and consented to participate. Child-Pugh (CP) score was calculated for all patients. GFR was calculated usingserum creatinine, serum cystatin-C, and 99m TC-DTPA clearance with the lastone serving as the gold standard. The area under curve (AUC) on receiveroperatingcharacteristic curves (ROC) were used to assess the diagnostic accuracyof each calculated GFR with that measured by DTPA., Results: Fourty-eight patients were enrolled (32 males, 66.7%). Nine were in class-A,20 in class-B and 19 in class-C of CP. Cystatin-C did not perform well in predictingthe true GFR, while serum creatinine performed relatively accurately atGFR<80ml/min (AUC=0.764, p=0.004). Serum creatinine at a cutoff of 1.4 mg/dl was 20% sensitive & 92% specific and with at a cutoff of 0.9 mg/dl was 77%sensitive & 72% specific for diagnosis of impaired renal function. Cystatin-Ccould not predict GFR effectively even after stratification for CP score, gender,and BMI. Serum creatinine could predict GFR<65ml/min in females (ROCcurve AUC=0.844, p=0.045). In those with BMI>20 kg/m2 a GFR<80 ml/mincould also be predicted by serum creatinine (ROC curve AUC=0.739, p=0.034).It also could predict GFR<80ml/min in patients with CP class A & B (ROC curveAUC=0.795, p=0.01), but not in patients with CP class C., Conclusion: Neither serum creatinine nor Cystatin-C are good predictors of GFR in cirrhoticpatients, although serum creatinine seems to perform better in selectedsubgroups.

Background: Proton pump inhibitors (PPIs) are the most effective agents available for reducing acid secretion. They are used for medical treatment of various acid-related disorders. PPIs are used extensively and for extended periods of time in gastroesophageal reflux disease (GERD). A troublesome issue regarding maintenance therapy has been the propensity of PPI-treated patients to develop chronic atrophic gastritis while on therapy that could theoretically lead to an increased incidence of gastric cancer. In addition, animal studies have raised concern for development of enterochromaffin-like cell hyperplasia and carcinoid tumors in the stomachs of mice receiving high dose PPIs. Current literature does not provide a clear-cut conclusion on the subject and the reports are sometimes contradictory. Therefore, this study is a systematic review of the available literature to address the safety of long-term PPI use and its relation to the development of malignant/premalignant gastric lesions., Methods: A literature search of biomedical databases was performed. The reference lists of retrieved articles were reviewed to further identify relevant trials. We hand-searched the abstracts of the American Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW) from 1995 to 2013. Only randomized clinical trials (RCTs) that used PPIs as the primary treatment for at least six month versus no treatment, placebo, antacid or anti-reflux surgery (ARS) were included. Two reviewers independently extracted the data. Discrepancies in the interpretation were resolved by consensus. All analyses of outcomes were based on the intention-to-treat principle. We performed statistical analysis using Review Manager software. The effect measure of choice was relative risk (RR) for dichotomous data., Results: Six RCTs with a total of 785 patients met the inclusion criteria. Two multicenter RCTs compared Esomeprazole with placebo. One RCT compared omeprazole with ARS. Two RCTs compared omeprazole with ranitidine and one RCT compared lansoprazole with ranitidine. Four of the included RCTs had moderate risk of bias and two had low risk of bias. The number of patients with increased corporal atrophy score, intestinal metaplasia score and chronic antral inflammation did not statistically differ between the PPI maintenance group and controls. Similar results were found when ECL-cell hyperplasia was assessed between the groups., Conclusions: Maintenance PPIs did not have an association with increased gastric atrophic changes or ECL-cell hyperplasia for at least three years in RCTs.

Background: Hepatocellular carcinoma is a major worldwide health problem, involving more than half a million new patients yearly, with a different incidence in different parts of the world. Hepatocellular carcinoma develops in about 80% of cirrhotic patients, and cirrhosis is considered the strongest predisposing factor for it. Surgical resection and liver transplantation are conventional treatment modalities that can offer long-term survival for patients with hepatocellular carcinoma., Objectives: To assess the benefits and harms of surgical resection compared with those of liver transplantation in patients with hepatocellular carcinoma., Search Methods: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded (SCI-EXPANDED) at ISI Web of Science (last search February 2013). We also searched the abstracts from annual meetings of the American Society of Clinical Oncology, the American Association for the Study of Liver Diseases (AASLD), and the European Association for the Study of the Liver (EASL), provided through The Cochrane Hepato-Biliary Group until February 2013., Selection Criteria: Randomised clinical trials comparing surgical resection and hepatic transplantation., Data Collection and Analysis: The search strategies were run and two authors individually evaluated whether the retrieved studies fulfilled the inclusion criteria., Main Results: No randomised clinical trials comparing surgical resection and liver transplantation as the major methods of treating hepatocellular carcinoma were found., Authors' Conclusions: There are no randomised clinical trials comparing surgical resection and liver transplantation for hepatocellular carcinoma treatment.

Background: This study assesses the potential effect of Lactobacillus reuteri as a single strain probiotic preparation (Biogaia®) on irritable bowel syndrome (IBS)., Methods: Patients diagnosed with IBS who fulfilled Rome III criteria and consented to participate in this study were randomized to receive either the probiotic or an identical placebo once daily for four weeks. Patients used a questionnaire to record any symptoms and adverse reactions over a one-week run-in period and during the final two weeks of intervention. For each group, we calculated the differences between mean scores of the variables and compared the results between groups., Results: Frequency of defecation increased in the Biogaia® group and decreased in the placebo group meaningfully. But There were no significant difference in the two groups in other terms of bloating, sense of urgency for defecation, abdominal pain, stool shape, quality of defecation, sense of incomplete evacuation, and treatment satisfaction., Conclusion: The frequency of defecation increased in the Biogaia® group and decreased in the placebo group, however this study did not classify patients according to diarrhea or constipated subgroups, the efficacy of this drug is not clear. Hence Lactobacillus reuteri was not better than placebo in controlling IBS symptoms in this study. However, considering the significant placebo effect in IBS patients, it may be necessary to conduct studies with larger numbers of participants to better assess the possible beneficial effects of Biogaia.

Background: This study has been designed to investigate the clinical association between gastro esophageal reflux disease (GERD) and chronic otitis media (COM) in adults and also the role of GERD treatment on the outcome of COM surgery., Methods: In a randomized clinical trial, 58 patients with COM who were candidates for surgery were evaluated for GERD and divided in two groups; GERD positive (case) and GERD negative (control) patients. The GERD positive patients were randomized to either receiving medical treatment for GERD or not prior to surgery. The surgical outcomes were assessed at 3 and 6 months after COM surgery in the three groups., Results: Fifty-eight (26 males) patients were enrolled. Forty-two (72.4%) of these had GERD according to a validated questionnaire. Three months after surgery auditory recovery in GERD negative patients was significantly higher [16(100%)] than those suffering from GERD [28 out of 42 (66.7%)], p=0.008. The figures remained similar at six months follow up as well (100 % vs. 72.5% in GERD negative and positive patients respectively, p=0.002).In the GERD-positive group, 8 of 18 (44.4%) patients who did not receive GERD treatment before tympanomastoidectomy recovered after three months whereas, while 20 of 24 (83.3%) patients who received GERD treatment recovered during this time (p<0.001). At six months 44.4% of non-treated GERD patients had auditory recovery as compared to 95.5 % of those treated for GERD (p<0.01)., Conclusion: Our data show that the effect of GERD on the outcome of COM surgery may be considerable. On the other hand, treating COM patients for GERD medically for two months before tympanoplasty improves the surgical outcomes. Therefore, we suggest that COM patients be evaluated for GERD before undergoing tympanoplasty and if GERD is present, they be treated medically for a couple of months before undergoing surgery.

Objectives: To investigate the association between opium use and subsequent risk of death., Design: Prospective cohort study., Setting: The Golestan Cohort Study in north-eastern Iran collected detailed validated data on opium use and other exposures at baseline. Participants were enrolled between January 2004 and June 2008 and were followed to May 2011, with a follow-up success rate of over 99%., Participants: 50,045 participants aged 40-75 at baseline., Main Outcomes: Mortality, all cause and major subcategories., Results: 17% (n = 8487) of the participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 2145 deaths were reported. The adjusted hazard ratio for all cause mortality associated with ever use of opium was 1.86 (95% confidence interval 1.68 to 2.06). Opium consumption was significantly associated with increased risks of deaths from several causes including circulatory diseases (hazard ratio 1.81) and cancer (1.61). The strongest associations were seen with deaths from asthma, tuberculosis, and chronic obstructive pulmonary disease (11.0, 6.22, and 5.44, respectively). After exclusion of people who self prescribed opium after the onset of major chronic illnesses, the associations remained strong with a dose-response relation., Conclusion: Opium users have an increased risk of death from multiple causes compared with non-users. Increased risks were also seen in people who used low amounts of opium for a long period and those who had no major illness before use.

Inflammatory bowel disease (IBD) is the term used for a group of diseases with yet unknown etiology, prevalence of which is increasing almost everywhere in the world. The disease was almost non-existent four decades ago in the east, including the middle-east, while now a days it is seen more and more. In addition to the increasing prevalence, our knowledge about its pathogenesis, clinical course, diagnosis, and treatment has changed dramatically over the past couple of decades. This has changed our concept of this group of diseases, their diagnosis, treatment, and treatment goals. Considering the vast literature on the subject, it is timely to review major topics in IBD with a look on the regional progress and knowledge as well. This essay is aimed to cover this task.

Almost four decades ago, an eminent physician, outstanding mentor and scholar, Professor Faramarz Ismail-Beigi (b. 1941) was appointed Chair of the Department of Internal Medicine at Shiraz Medical School. Soon, this proved to be the beginning of a golden era in medical education at that center. Professor Ismail-Beigi invited outstanding teachers and physicians to collaborate with him. Their efforts during the next decade laid a strong and unique foundation for medical education based on quality mentorship and role-modeling. In this paper, we briefly highlight the importance of mentorship in medicine and medical education, followed by a glance at the academic life and career of Professor Ismail-Beigi and his role as a prominent mentor at the Shiraz School of Medicine.

Although foreign body (FB) ingestion is relatively common,ingestion of a toothbrush is rare. We are reporting on a 26-year old female who had accidentally swallowed a toothbrush, which was successfully removed via endoscopy using a polypectomy snare.

Background: There is limited data on the natural history of autoimmune hepatitis (AIH) and on the long-term follow-up of AIH patients who have been referred for regular medical attention., Objectives: We evaluated the clinical presentation and natural history of AIH in a large cohort of type I AIH patients from Iran., Patients and Methods: Between 1997 and 2008, 102 patients were enrolled in the study. Patients were diagnosed using the International Autoimmune Hepatitis Group criteria and were followed up for an average of 60 months. Clinical and biochemical data were gathered from all the patients at both the beginning and the end of the follow-up period. Liver biopsy was performed in all patients before treatment, and the biopsies were performed in 28 patients after treatment., Results: Biochemical remission was achieved by 80 (79.4%) patients. Of these, 53 (66.5%) showed near-normal liver histology or liver function test results and sonogram. The remaining 27 (33.5%) patients also achieved clinical and biochemical remission, but developed compensated cirrhosis. After a period of remission, 24 patients (32.5%) relapsed. Among the 22 (21.6%) patients who showed ultimate treatment failure, 6 underwent orthotopic liver transplantation and 3 died of liver failure while awaiting a transplant. Sixteen (72.7%) of the 22 patients who did not respond to therapy were non-compliant with medications and had irregular follow-up. The overall 10-year survival rate in the cohort was 96%., Conclusions: Long-term survival in AIH patients is very good. Prompt diagnosis and appropriate first-line and salvage therapy that includes close follow-up will make liver transplantation a rare necessity in the treatment of this disease.

Background: Despite the rich literature on GERD, its cause and reason for increased prevalence remain obscure. Currently accepted mechanisms leave many questions unanswered. Nitrite chemistry at the GEJ is well described for carcinogenesis. Recent epidemiological and animal data have linked nitrates to GERD. "Nitrate reductase" of oral bacteria converts nitrates to nitrites. We hypothesized that nitrate reductase activity is higher in patients with erosive GERD, delivering more nitrite at the gastroesophageal-junction for a given nitrate intake., Aim: To compare oral nitrate reductase activity of erosive GERD patients with controls., Methods: Patients with erosive GERD and controls without GERD were enrolled. After overnight fasting, nitrite of oral cavity contents was measured at 1-min intervals for 3 min while incubating a 10-mg nitrate-N/L solution in the mouth. Nitrate reductase activity was calculated and compared between groups., Results: Eleven cases (ten males, mean age: 42.6 ± 11.7 year) and ten controls (eight males, mean age: 37.6 ± 9.2 year) were enrolled. Mean nitrate reductase activity was 3.23 ± 0.99 vs. 2.30 ± 0.83 "μg nitrite-N formed/person/minute" in cases and controls, respectively (p = 0.03)., Conclusions: Oral nitrate reductase activity in erosive GERD patients is higher than controls. Therefore, any dietary nitrate load generates more nitrite in these patients. This excess nitrite at the gastroesophageal junction, may potentially contribute to the development of GERD. This is the first report linking oral nitrite production to erosive GERD in man. We suggest that a "nitrate hypothesis" may answer yet unanswered questions about GERD pathogenesis. If confirmed, it may change our understanding of mechanisms of GERD and provide novel therapeutic targets.

Objectives: We investigated whether using demographic characteristics and alarm symptoms can accurately predict cancer in patients with dyspepsia in Iran, where upper GI cancers and H. pylori infection are common., Methods: All consecutive patients referred to a tertiary gastroenterology clinic in Tehran, Iran, from 2002 to 2009 were invited to participate in this study. Each patient completed a standard questionnaire and underwent upper gastrointestinal endoscopy. Alarm symptoms included in the questionnaire were weight loss, dysphagia, GI bleeding, and persistent vomiting. We used logistic regression models to estimate the diagnostic value of each variable in combination with other ones, and to develop a risk-prediction model., Results: A total of 2,847 patients with dyspepsia participated in this study, of whom 87 (3.1%) had upper GI malignancy. Patients reporting at least one of the alarm symptoms constituted 66.7% of cancer patients compared to 38.9% in patients without cancer (p<0.001). Esophageal or gastric cancers in patients with dyspepsia was associated with older age, being male, and symptoms of weight loss and vomiting. Each single predictor had low sensitivity and specificity. Using a combination of age, alarm symptoms, and smoking, we built a risk-prediction model that distinguished between high-risk and low-risk individuals with an area under the ROC curve of 0.85 and acceptable calibration., Conclusions: None of the predictors demonstrated high diagnostic accuracy. While our risk-prediction model had reasonable accuracy, some cancer cases would have remained undiagnosed. Therefore, where available, low cost endoscopy may be preferable for dyspeptic older patient or those with history of weight loss.

BACKGROUND Eosinophilic gastroenteritis (EG) is a rare inflammatory disorder of the gastrointestinal (GI) tract. There have been several case series of patients with EG from the western world and East Asia. However, there has not been a report of patients with EG from the Middle East region. The aim of this study is to describe clinical characteristics and treatment response in a series of EG patients from Iran. METHODS We retrospectively reviewed charts with a diagnosis of EG from 1997 to 2010 at Shariati Hospital and the private clinics of the authors. Clinical characteristics of the patients were evaluated, and the treatment response and relapse rate were assessed. RESULTS Twenty-two patients (9 male) with EG were identified. Mean age of the patients was 45.1±15.5 (range: 27-75) years. Median duration between symptom onset and diagnosis was 12 (range 1- 48) months. Twenty (90%) patients had mucosal involvement, one (5%) had muscular involvement and one (5%) had subserosal involvement. Patients were followed for a median duration of 36.5 (range 4-123) months. Two patients had spontaneous remission with supportive care. The remaining 20 patients responded well to oral corticosteroid treatments. The relapse rate was 33%. Episodes of relapse were successfully controlled with a repeat course of corticosteroids. Two patients with several relapses required maintenance treatment with azathioprine. CONCLUSION The clinical characteristics and treatment responses of EG patients from Iran are similar to reports from other parts of the world. Patients need to undergo close follow up after treatment to detect early signs of relapse.

Background: Gastro-esophageal reflux disease (GERD) has become very common in the past three decades. The reason for this, as well as its exact pathophysiologic mechanisms are yet unknown. In this ecologic study we assessed the relation between water nitrate content and prevalence of GERD in Tehran, Iran., Methods: We determined the prevalence of acid regurgitation, heartburn or any of them occurring on a frequent (at least weekly) or infrequent basis in areas with different water nitrate. The areas for nitrate were defined as below: <50 mg nitrate/L, 50-74 mg/L, 75-100 mg/L, and >100 mg/L. Frequency of each symptom was assessed in each area and compared. Adjustment for age, sex, education, NSAID-consumption, BMI, smoking, history of GERD in first degree relatives and spouse was done in a multivariate model., Results: People living in areas with water nitrate content more than 100mg/L had a higher chance of suffering from frequent AR than those living in areas with water nitrate less than 100mg/L (25.5% vs. 12.0%, OR: 2.53, 95% CI: 1.36-4.73, P=0.006). After adjustment for the named factors, the relationship remained significant (OR: 3.65, 95% CI: 1.32-10.09). The relation for frequent heartburn or infrequent symptoms was not significant., Conclusion: In this ecologic study, we found a relation between experiencing frequent AR and drinking or cooking with water containing more than 100mg nitrate/L. Considering our current knowledge, if we put dietary nitrate into the puzzle of increased prevalence and/or pathophysiology of GERD, it can theoretically answer several questions. Hence we propose a nitrate-hypothesis for GERD pathogenesis.

Background: Hepatic hydatid cyst is an important public health problem in parts of the world where dogs are used for cattle breeding. Management of uncomplicated hepatic hydatid cysts is currently surgical. However, the puncture, aspiration, injection, and re-aspiration (PAIR) method with or without benzimidazole coverage has appeared as an alternative over the past decade., Objectives: To assess the benefits and harms of PAIR with or without benzimidazole coverage for patients with uncomplicated hepatic hydatid cyst in comparison with sham/no intervention, surgery, or medical treatment., Search Strategy: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, DARE, and ACP Journal Club and full text searches were combined (all searched October 2010). Reference lists of pertinent studies and other identified literature were scanned. Researchers in the field were contacted., Selection Criteria: Only randomised clinical trials using the PAIR method with or without benzimidazole coverage as the experimental treatment of uncomplicated hepatic hydatid cyst (ie, hepatic hydatid cysts, which are not infected and do not have any communication with the biliary tree or other viscera) versus no intervention, sham puncture (ie, performing all steps for puncture, pretending PAIR being performed, but actually not performing the procedure), surgery, or chemotherapy were included., Data Collection and Analysis: Data were independently extracted, and the risk of bias in each trial was assessed by the authors. Principal authors of the trials were contacted to retrieve missing data., Main Results: We found no randomised clinical trials comparing PAIR versus no or sham intervention. We identified only two randomised clinical trials, one comparing PAIR versus surgical treatment (n = 50 participants) and the other comparing PAIR (with or without albendazole) versus albendazole alone (n = 30 participants). Both trials were graded as 'adequate' for allocation concealment; however, generation of allocation sequence and blinding methods were 'unclear' in both. Compared to surgery, PAIR plus albendazole obtained similar cyst disappearance and mean cyst diameter with fewer adverse events (32% versus 84%, P < 0.001) and fewer days in hospital (mean + SD) ( 4.2 + 1.5 versus 12.7 + 6.5 days, P < 0.001). Compared to albendazole, PAIR with or without albendazole obtained significantly more (P < 0.01) cyst reduction and symptomatic relief., Authors' Conclusions: PAIR seems promising, but there is insufficient evidence to support or refute PAIR with or without benzimidazole coverage for treating patients with uncomplicated hepatic hydatid cyst. Further well-designed randomised clinical trials are necessary to address the topic.

Background: Antibodies against hepatitis B surface antigen (HBs) wane over time after vaccination for hepatitis B (HB); hence, the duration of protection provided by the vaccine is still unknown but may be evaluated indirectly by measuring the anamnestic immune response to booster doses of vaccine., Objectives: To assess the benefits and harms of booster dose hepatitis B vaccination for preventing HB infection., Search Strategy: We searched The Cochrane Hepato-biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 4, 2010) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to May 2010. We also contacted authors of articles and manufacturers., Selection Criteria: Randomised clinical trials addressing anamnestic immune response to booster of HB vaccine five years or more after primary vaccination in apparently healthy participants, vaccinated in a 3-dose or 4-dose schedules of HB vaccine without receiving additional dose or immunoglobulin., Data Collection and Analysis: Two authors made the decisions if the identified publications on studies met the inclusion criteria or not. Primary outcome measures included the proportion with anamnestic immune response in non-protected participants and signs of hepatitis B virus infection. Secondary outcomes were the proportion with local and systemic adverse event events developed following booster dose injection. Weighted proportion were planned to be reported with 95% confidence intervals., Main Results: There were no eligible randomised clinical trials fulfilling the inclusion criteria of this review., Authors' Conclusions: We were unable to identify randomised clinical trials on the topic. We need randomised clinical trials to formulate future booster policies for preventing hepatitis B infection.

Aim: To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both., Methods: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4 +/- 11.5 years) met Rome II or Rome III criteria (depending on the year of diagnosis) for IBS. 2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings. We assessed other functional symptoms (epigastric pain, nausea, vomiting, belching, constipation and diarrhea) in patients suffering from GERD, IBS or both., Results: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4 +/- 10.3 years) also had GERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) = 3.2, 95% confidence interval (CI): 2.9-3.7, P < 0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR = 3.6, 95% CI: 3.1-4.3, P < 0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P < 0.05)., Conclusion: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.

The duration of protection provided by hepatitis B vaccine is still unknown but can be estimated through long-term follow-up studies. Electronic databases and conference databases to December 2008 were searched. Reference lists of articles were screened and the studies authors and manufacturers were contacted for additional unpublished references. Randomized clinical trials and prospective cohort studies addressing the long-term protective effect of hepatitis B vaccine were included in this meta-analysis. We assessed 42 separate cohorts involving overall 11,090 subjects; 34 cohorts involving 9356 subjects were included in the final meta-analysis. Results indicate that the overall cumulative incidence of HBV breakthrough infection 5-20 years post-primary vaccination was 0.007 [95% CI: 0.005 to 0.010] with a variation among studies from 0 to 0.094. Available data do not allow us to exclude an increased risk for infection with time since vaccination. We conclude that the protection provided by three or four doses of monovalent HB vaccine persists for at least two decades in the great majority of immunocompetent individuals. Additional studies are needed for assessing vaccine efficacy for longer periods of time and the need of booster doses in different subgroups of population.

Background: Osteoporosis has been frequently reported in patients with inflammatory bowel diseases, especially Crohn's disease., Methods: All consecutive Crohn's disease patients who attended the GI Clinics at Shariati Hospital, Tehran, Iran, from 2004 to 2007 were evaluated. A BMD-DEXA assessment was performed for all patients. Among those patients diagnosed with osteoporosis (T score

Background: Despite claims of rarity, some studies indicate that the prevalence of inflammatory bowel disease has increased in Iran during the past decades. Establishment of a registry and the clinical characteristics are presented in this study., Methods: Two hundred ninety-three patients with ulcerative colitis and 207 with Crohn's disease, referred to tertiary referral gastrointestinal centers in Tehran from 2004 through 2007, were assessed. Demographic and clinical features, intestinal and extraintestinal manifestations, inflammatory bowel disease in relatives, measles infection and vaccination, nutrition during infancy, and drugs and surgical interventions were assessed., Results: The mean+/-SD age at the diagnosis was 33.8+/-12.9 years in Crohn's disease and 37.1+/-13.7 years in ulcerative colitis. Male:female ratio was 0.9:1.0 for Crohn's disease and 0.7:1.0 for ulcerative colitis. A total of 177 (85.5%) patients with Crohn's disease, and 254 (86.7%) patients with ulcerative colitis had never smoked. Measles vaccination was mentioned in 150 (72.5%) of Crohn's disease and 214 (73%) of ulcerative colitis patients. Breastfeeding during infancy was reported in 178 (86%) and 257 (87.7%) of Crohn's disease and ulcerative colitis patients, respectively. Appendectomy was reported in 37 (17.9%) of Crohn's disease and 16 (5.5%) of ulcerative colitis patients, whereas tonsillectomy was reported in 11.6% of each group., Conclusion: Demographic and clinical characteristics of inflammatory bowel disease patients are similar to that of other developing countries, in this study, more inflammatory bowel disease cases have been assessed in comparison with previous studies, which may be due to different time scales of socioeconomic evolution and environmental factors in Iran.

Background: Cancer registries in the 1970s showed that parts of Golestan Province in Iran had the highest rate of oesophageal squamous cell carcinoma (OSCC) in the world. More recent studies have shown that while rates are still high, they are approximately half of what they were before, which might be attributable to improved socio-economic status (SES) and living conditions in this area. We examined a wide range of SES indicators to investigate the association between different SES components and risk of OSCC in the region., Methods: Data were obtained from a population-based case-control study conducted between 2003 and 2007 with 300 histologically proven OSCC cases and 571 matched neighbourhood controls. We used conditional logistic regression to compare cases and controls for individual SES indicators, for a composite wealth score constructed using multiple correspondence analysis, and for factors obtained from factors analysis., Results: We found that various dimensions of SES, such as education, wealth and being married were all inversely related to OSCC. The strongest inverse association was found with education. Compared with no education, the adjusted odds ratios (95% confidence intervals) for primary education and high school or beyond were 0.52 (0.27-0.98) and 0.20 (0.06-0.65), respectively., Conclusions: The strong association of SES with OSCC after adjustment for known risk factors implies the presence of yet unidentified risk factors that are correlated with our SES measures; identification of these factors could be the target of future studies. Our results also emphasize the importance of using multiple SES measures in epidemiological studies.

Background: The molecular and cellular mechanisms linking chronic inflammation and gastrointestinal malignancy are not known with certainty., Aim: To investigate changes in potential causative factors during progression of esophagus cancer in a population living in high-risk area in Iran., Subjects: Formalin-fixed, paraffin-embedded esophageal specimens (n=87) from patients with gastroesophageal reflux disease (GERD), Barrett's metaplasia, adenocarcinoma (ADC) and squamous cells carcinoma (SCC) were collected based on their pathological diagnosis., Methods: Immunohistochemical (IHC) technique was used to study tissue accumulation of P53, P21, cyclooxygenase-2 (COX-2), glutathione S-transferase-P (GST-Pi) and nitrotyrosine (NT) in patients and controls., Results: P53 expression was not detected in esophageal tissues from normal and GERD samples, whereas it was found positive in Barrett's, ADC, and SCC samples. P21 positive sample was relatively higher in ADC patients as compared to that in SCC (ADC: 52.6%; SCC: 25%). GST-Pi expression was equally accumulated in all the samples. NT was predominantly expressed in ADC (72.7%). COX-2 expression was significantly higher in Barrett's (60.0%) and ADC (66.6%) as compared to that in GERD, SCC and normal. These data were further confirmed by detecting the scores of immunostainings in all the positive samples., Conclusion: The pathological changes in ADC and SCC samples which were associated with increasing frequency of NT and COX-2 provides further evidence for involvement of these inflammatory factors in progression of esophagus cancer.

In a recently published paper in the "British Medical Journal", a joint collaboration of well-known international scientists represented by Islami et al. has tackled this issue.1 In a well-designed, laborious case-control study in Golestan, Iran, they looked at 300 cases of esophageal SCC and 571 age and sex matched neighborhood controls, assessed the temperature of the commonly used drink "tea" among them and compared it between the two groups. After adjusting for several confounders including ethnicity, daily vegetable intake, alcohol consumption, tobacco or opium use, duration of residence in rural areas, education level and car ownership (the latter two as indices of socio-economic status), they found that consuming hot tea is associated with significantly increased chance of developing esophageal SCC. The adjusted odds ratio(OR) for developing esophageal SCC in those who reported drinking "very hot tea" was 8.16 (95% CI: 3.93 to 16.91) as compared to those taking warm or lukewarm tea (P<0.001) and for those drinking "hot" tea the adjusted OR was 2.07 (95% CI: 1.28 to 3.35). According to Islami et al., 21.1% and 36.2% of the cases drank their tea "very hot" or "hot", respectively. Self-claim of "hot", "very hot", and "warm or "lukewarm" tea drinking correlated with the claimed time from pouring tea to its drinking by the individual (weighted kappa statistics: 0.69). They did not find any correlation between amount of tea consumed and development of esophageal SCC. They have also reported limited data of tea temperature measurement in addition to the self claims of tea drinking habits (as mentioned for the case-control study) from a large on-going cohort study in the same region. The authors conclude that it is probably the "hotness" rather than the "tea" which is responsible for this increased chance of SCC of esophagus. In an accompanying editorial, Whiteman suggests that people drink their tea at least 5 minutes after pouring it in their cups.

Background: Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood., Methodology/principal Findings: Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD., Conclusion: This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.

Background: Increased duodenal intraepithelial lymphocytes is a key histological finding in celiac disease. Available studies suggest a wide normal range (10 - 40 intraepithelial lymphocytes /100 epithelial cells, EC). We assessed the normal range of distal duodenal intraepithelial lymphocytes., Methods: Biopsies from the normal-looking distal duodenum from individuals referring for endoscopy for reasons other than intestinal pathologies were stained with hematoxylin-eosin and immuno-histochemistry (immunohistochemistry, CD45). At least 1000 cells from the tip and body of the villi were assessed. Villous height to crypt depth ratio was calculated., Results: Fifty individuals were enrolled. Four were excluded (inadequate biopsies). Mean intraepithelial lymphocyte count was similar in villous tip and body. In the whole villous, upper limit of normal (mean+2SD) was 35 intraepithelial lymphocytes/100EC (95% CI: 31 - 39) in immunohistochemistry and 34 intraepithelial lymphocytes/100EC (95%CI: 29 - 37) in H&E staining. The villous height to crypt depth ratio was 3.9. Hematoxylin-eosin and immunohistochemistry had excellent agreement., Conclusion: Intraepithelial lymphocyte counts less than 35/100EC in IHC and 34/100EC in hematoxylin-eosin staining can be considered normal. Counts between 36-39 (immunohistochemistry) and 35 - 37 (hematoxylin-eosin) are borderline and more than 39 (immunohistochemistry) and 37 (hematoxylin-eosin) are increased. The hematoxylin-eosin staining method seems adequate for clinical purposes. Regional differences in the normal upper limit for intraepithelial lymphocytes as well as changes over time should be considered when interpreting duodenal biopsies.

Background: The prevalence of gastroesophageal reflux disease (GERD) in Asian populations is reported to be lower than that in the West. Population-based data on the prevalence and symptom profile of GERD in developing Caucasian countries is lacking. Our objective was to determine the prevalence of gastrointestinal symptoms and clinical spectrum of GERD in Tehran, northern Iran and their association with patient characteristics., Methods: One thousand seven hundred telephone numbers were randomly selected from Tehran telephone directory using a simple random method. A two-step screening telephone survey was then performed. In each answered call a second rapid survey was done to select a subject 18-65 years old from that household. A validated questionnaire was then filled out for that individual. Patient characteristics (age, education, and gender) and history of acid regurgitation and heartburn during the last week, as well as the previous three months were inquired about., Results: Of the 1,700 selected numbers, 278 either did not answer or did not have an eligible case; 220 refused to participate. A total of 1,202 subjects (42% males, mean age: 36 years, range: 18-65 yr) were surveyed. The prevalence of heartburn occurring monthly, weekly, and daily was 4.7% (CI95%: 3.5-6.0%), 1.6% (CI95%: 1.0-2.5%), and 0.6% (CI95%: 0.3-1.3%), respectively. The corresponding figures for acid regurgitation were 15.6% (CI95%: 13.6-17.7%), 5.7% (CI95%: 4.4-7.1%) and 1.5% (CI95%: 0.9-2.4%), respectively. The prevalence of GERD, defined as heartburn and/or acid regurgitation experienced daily, weekly and monthly was 1.9% (CI95%: 1.2-2.9%), 6.8% (CI95%: 5.4-8.3%), and 18.4% (CI95%: 16.2-20.6%). There was no relationship between the prevalence of GERD and either gender, age, or education., Conclusion: Monthly GERD symptoms occur in 18.4% of the general population in Tehran. Acid regurgitation is more common (4 - 5 times) than heartburn. Gender, age, and level of education do not affect the prevalence of GERD symptoms in the community studied.

Objective: Population-based data on gastroesophageal reflux disease (GERD) in Iran are limited. Current study is going to determine the prevalence of GERD in Tehran, Iran, and its association with potential risk factors., Methods: In this cross-sectional study, a random clustered sample of Tehran province permanent households was selected from the latest postcodes. Data were collected by direct interview for each person aged 18-65 yr. GERD was defined as the existence of at least weekly episodes of heartburn and/or acid regurgitation during the last 6 months. All participants were asked about past and recent sanitary conditions, oral hygiene, and smoking. Odds ratios and 95% confidence intervals (CI) were calculated using multivariable analysis., Results: Interview was performed with 2,561 eligible subjects (42.3% men). Response rate was 84.8%. The prevalence of GERD was 21.2% (95% CI 18.7-23.7). According to multivariable logistic regression analyses, individuals whose drinking water was obtained from well or tank during childhood were more prone to experience GERD symptoms (OR 1.54, 95% CI 1.03-1.77 and OR 2.46, 95% CI 1.53-3.96, respectively). We also detected significant associations with increasing number of missing teeth (P value for linear trend = 0.02) and history of unpurified water consumption during past 10 yr (P < 0.001). Current smokers had a higher prevalence of reflux (OR 1.82, 95% CI 1.32-2.51)., Conclusion: The prevalence of GERD in our Iranian population was considerably higher than that reported from other Asian studies approaching western figures. GERD prevalence was significantly associated with the history of unpurified water consumption, poor sanitary conditions of childhood, number of missing teeth, and smoking in this population.

Background: Furazolidone has been effective against Helicobacter pylori in Iran, with no resistance, but with intolerable side effects in the second week. One-week regimens have not been useful here. We compared the efficacy and side effect profiles of three anti-H. pylori regimens., Methods: Patients with peptic ulcer disease and positive H. pylori infection were randomly allocated into three groups. The patients in group A received omeprazole 20 mg + amoxicillin 1g + metronidazole 500 mg, and bismuth subcitrate 240 mg twice daily each, for two weeks; the patients in group B received the same regimen but metronidazole was replaced by furazolidone 200 mg twice daily; and the patients in group C received regimen B for the first week and regimen A for the second week. H. pylori eradication was verified with 13C-urea breath test at the tenth week., Results: Three hundred and fourteen patients were enrolled; 107, 104, and 103 patients in groups A-C, respectively but 278 patients completed the study. Seven, three, and six patients discontinued their medication in groups A-C, respectively. Fever, dizziness, and weakness were more common in group B than group C (P < 0.05). Vomiting, pruritus, and rash were more common in group C than group A (P < 0.05). Per-protocol eradication rates were 83.1%, 95.2%, and 95.3% in groups A-C, respectively (P = 0.005, groups A and C). Intention to treat eradication rates were 74.5%, 87.0%, and 86.6% in groups A-C, respectively (P = 0.02, groups A and C)., Conclusion: One-week furazolidone followed by one-week metronidazole regimen is as efficient as two-week furazolidone regimen but with fewer side effects. Furazolidone-based regimens are superior to metronidazole-based ones for H. pylori eradication in Iran.

Background: Los Angeles classification is widely adopted for reporting endoscopic gastroesophageal reflux disease. We assessed the inter- and intra-observer variability of the Los Angeles classification., Methods: Still images (n = 254) of the lower esophagus were presented to 9 gastroenterologists (6 experts and 3 trainees) and they were asked to report the images according to the Los Angeles classification. After 2 weeks the images were reordered and they were asked to report them again. Kappa statistic was calculated for intra- and inter-observer variability., Results: The kappa for intra-observer agreement was 0.54 (attendings: 0.54; trainees; 0.55; P = not significant) and the inter-observer agreement was 0.22 (attendings: 0.20; trainees: 0.31; P = 0.027). The inter- and intra-observer kappa values in differentiating nonerosive from erosive cases were 0.22 (attendings: 0.21; trainees: 0.31, P = not significant) and 0.57 (attendings: 0.58; trainees: 0.55, P = not significant), respectively., Conclusion: According to our data, the Los Angeles classification has acceptable intra-observer variability, both for detecting presence or absence of erosions and for differentiating between different degrees of esophagitis, while its inter-observer performance seems to be less acceptable. It may be reasonable and timely to have another look at the Los Angeles classification to see whether its performance can be improved even further.

Objective: To estimate the prevalence and clinical spectrum of gastroesophageal reflux disease (GERD) in a young population and evaluate the risk factors., Methods: This cross-sectional study using a reliable and valid questionnaire was performed during June and July 2005, on randomized selection of 620 students form Azad University of Tabriz. Gastroesophageal reflux disease was defined as at least weekly heartburn and/or acid regurgitation., Results: Mean age (+/- SD) of the responders was 22.48 +/- 1.98 years. The prevalence of heartburn and/or acid regurgitation experienced at least weekly was 6.3% and monthly was 13%. The severity of symptoms was mainly of a mild to moderate degree. There was no difference in prevalence of any GERD symptom between 2 genders and it was not associated with age of the study population. A frequent symptom of GERD was reported more among subjects with atypical symptoms. There was no relation between marriage status and prevalence of GERD. On the other hand, GERD was less common among subjects with no family history of upper gastrointestinal disease and students in higher rank fields. Increased body mass index (but no recent weight gain or lose) and drinking coffee and tea was associated with higher prevalence of GERD symptoms., Conclusion: This study as the first study using a valid questionnaire reveals a high prevalence of frequent GERD symptoms in a young population of Tabriz. Atypical symptoms should be considered in this area.

Background: Hepatic hydatid cyst is an important public health problem in parts of the world where dogs are used for cattle breeding. Management of uncomplicated hepatic hydatid cysts is currently surgical. However, the puncture, aspiration, injection, and re-aspiration (PAIR) method with or without benzimidazole coverage has appeared as an alternative to surgery over the past decade., Objectives: To assess the benefits and harms of PAIR with or without benzimidazole coverage for patients with uncomplicated hepatic hydatid cyst in comparison with sham/no intervention, surgery, or medical treatment., Search Strategy: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register in The Cochrane Library, MEDLINE, EMBASE, DARE, and ACP Journal Club and full text searches were combined (all searched October 2004). Reference lists of pertinent studies and other identified literature were scanned. Researchers in the field were contacted., Selection Criteria: Only randomised clinical trials using the PAIR method with or without benzimidazole coverage as the experimental treatment of uncomplicated hepatic hydatid cyst (ie, hepatic hydatid cysts which are not infected and do not have any communication with the biliary tree or other viscera) versus no intervention, sham puncture (ie, performing all steps for puncture, pretending that PAIR is being performed, but actually not performing the procedure proper), surgery, or chemotherapy were included., Data Collection and Analysis: Data were independently extracted and methodological quality of each trial was assessed by the authors. Principal authors of the trials were contacted to retrieve missing data., Main Results: We found no randomised clinical trials comparing PAIR versus no or sham intervention. We identified only two randomised clinical trials, one comparing PAIR versus surgical treatment (n = 50) and the other comparing PAIR (with or without albendazole) versus albendazole alone (n = 30). Both trials were graded as 'adequate' for allocation concealment; however, generation of allocation sequence and blinding methods were 'unclear' in both of them. Compared to surgery, PAIR plus albendazole obtain similar cyst disappearance and mean cyst diameter with fewer adverse events (32% versus 84%, P < 0.001) and fewer days in hospital (mean + SD) ( 4.2 + 1.5 versus 12.7 + 6.5 days, P < 0.001). Compared to albendazole, PAIR with or without albendazole obtain significantly more often (P < 0.01) cyst reduction and symptomatic relief., Authors' Conclusions: PAIR seems promising, but there is insufficient evidence to support or refute PAIR with or without benzimidazole coverage for treating patients with uncomplicated hepatic hydatid cyst. Further well-designed randomised clinical trials are necessary to address the topic.

Background and Aim: Helicobacter pylori (HP) infection is one of the most prevalent human infections and has been implicated as a predisposing factor in gastric cancer, chronic active gastritis, duodenal ulcer, gastric ulcer and gastric lymphoma. Reinfection after successful eradication is quite uncommon in adults. In the only study carried out in Iran, a reinfection rate of 19.1% after 1 year has been reported. We studied the rate of reinfection 3 years after successful HP eradication., Methods: All patients who had undergone HP eradication 3 years before the study and had successful eradication verified by a negative (14)C urea breath test (UBT) 1 year after eradication were invited to complete a questionnaire and undergo another UBT. In addition, spouses and the offspring of those testing positive were offered an UBT., Results: Ninety-eight patients were enrolled (49% male). Mean age was 44 +/- 13 years (range: 18-75 years). Twenty patients (20.4%) had a positive UBT. Epigastric burning (25%vs 69%) and pyrosis (50%vs 67%) were seen less commonly in those who were HP free at 3 years compared to those who tested positive for HP., Conclusions: According to our data, in our region the HP reinfection rate is 20.4% 3 years after successful eradication.

The impact of treatment on progression of fibrosis in autoimmune hepatitis (AIH) is unknown. We assessed the changes in liver fibrosis before and after treatment among these patients. Nineteen AIH patients who had paired liver biopsies were studied. Of these, seven had been treated with 6 months of cyclosporine A and the rest with 6 months of prednisolone for induction of remission. Thereafter all had been maintained on azathioprine. Biopsy specimens before and after treatment were reviewed by one pathologist and scored by the Ishak method. Mean fibrosis stages before and after treatment were compared. Also, factors predicting significant fibrosis (stage > or =3) and cirrhosis (stage > or =5) at presentation were assessed. Mean interval between biopsies was 3.38 years. Mean fibrosis stage decreased from 4.53 to 2.16 following treatment (P < 0.001). Mean decrement in inflammatory grade was 8 scores (range, 4-10) in patients in whom fibrosis improved, and 2 scores (range, 0-4) in patients in whom fibrosis did not decrease after treatment (P < 0.001). ALT-to-platelet ratio was the best predictor of significant fibrosis and also cirrhosis. Fibrosis commonly improves after immunosuppressive treatment in AIH. ALT-to-platelet ratio can predict accurately the presence of significant fibrosis and cirrhosis in AIH.