BAT25, ACVR2, and TGFBR2 Mononucleotide STR Markers: A Triplex Panel for Microsatellite Instability Testing in Colorectal Tumors.

Background: Microsatellite instability (MSI) in colorectal cancer (CRC) patients is considered as a diagnostic and prognostic marker. MSI is a consequence of mismatch repair deficiency which is evaluated using the different microsatellite markers on the whole genome. In this pilot study, the diagnostic value of a novel triplex panel including three mononucleotide markers has been evaluated in comparison to the standard Promega kit for MSI testing in CRC patients with Amsterdam II criteria. Materials and Methods: DNA extracted from tumors and normal Formalin-Fixed Paraffin-Embedded (FFPE) tissues of index cases from 37 HNPCC (Hereditary non-polyposis colorectal cancer) families were evaluated for MSI state. Primer design for three markers, including BAT25, ACVR2, and TGFBR2, was performed using 19 nucleotides of the M-13 phage. The instability of each marker was assessed through fragment analysis in comparison with Promega kit markers for all patients. The sensitivity and specificity of each marker have been calculated. Results: The comparative evaluation of MSI in both tumors and normal adjacent FFPE tissues demonstrated a separate sensitivity as 100%, 83.3%, and 76.9% for BAT25, ACVR2, and TGFBR2, respectively, and 100% sensitivity in the form of a triplex. Moreover, the specificity for each of these three markers in MSI testing was estimated as 100%, separately and in the form of the triplex in comparison with the Promega pentaplex standard Kit. Conclusions: A high sensitivity and specificity for the novel triplex panel in MSI-testing were estimated among Iranian patients. More studies are recommended to confirm this panel as a diagnostic kit for MSI testing.

IS DAIRY FOODS RESTRICTION MANDATORY FOR INFLAMMATORY BOWEL DISEASE PATIENTS: A MULTINATIONAL CROSS-SECTIONAL STUDY.

BACKGROUND: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. OBJECTIVE: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. METHODS: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). RESULTS: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). CONCLUSION: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

A restrição de alimentos lácteos é obrigatória para pacientes com doença inflamatória intestinal? Estudo transversal multinacional / Is dairy foods restriction mandatory for inflammatory bowel disease patients: a multinational cross-sectional study

ABSTRACT Background: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. Objective: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. Methods: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). Results: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). Conclusion: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

RESUMO Contexto: O papel dos alimentos lácteos na doença inflamatória intestinal (DII) tem sido controverso e é discutível se os pacientes com DII devem ou não evitar leite e laticínios, bem como a relação entre esses alimentos e sintomas nesta população. Objetivo: Estudo transversal multicêntrico foi projetado para avaliar se é realmente necessário privar os pacientes com DII do consumo desta classe de alimentos. Métodos: Um estudo multicêntrico com 12 centros de referência em gastroenterologia de quatro países foi projetado para avaliar sintomas gastrointestinais após o consumo de alimentos lácteos em todos os ambulatórios de DII durante seis meses e comparar pacientes tratados nos mesmos centros sem DII. Resultados: No total, foram incluídos 1888 casos (872 pacientes com DII e 1016 casos sem DII. 56,6% dos participantes eram do sexo feminino com idade média de 40,1 anos. 79,8% dos participantes eram caucasianos e originalmente eram cidadãos de 10 países. A prevalência relativa de DII foi maior em africanos e indianos e a prevalência mais frequente de intolerância a alimentos lácteos observada nos asiáticos. Entre os pacientes com DII, 571 casos foram diagnosticados como colite ulcerativa e 189 participantes como doença de Crohn. A duração média do diagnóstico como DII foi de 6,8 anos (de 2 meses a 35 anos). Os sintomas de gastrointestinais mais prevalentes após o consumo de todos os alimentos lácteos foram inchaço e dor abdominal. No total, a intolerância aos alimentos lácteos e a deficiência de lactase foi mais prevalente entre os pacientes com DII em comparação com os casos sem DII (65,5% vs 46,1%, P=0,0001). A taxa de queixas gastrointestinais entre os pacientes com DII que não tinham histórico familiar de deficiência de lactase, histórico de sensibilidade alimentar ou ambos foram de 59,91%, 52,87% e 50,33% respectivamente e semelhantes aos casos sem DII (P=0,68, 0,98 e 0,99, respectivamente). Conclusão: A taxa de intolerância de alimentos lácteos entre pacientes com DII sem histórico familiar de deficiência de lactase ou histórico de sensibilidade alimentar é semelhante aos casos sem DII e provavelmente não há razão para privá-los dessa importante fonte de cálcio dietético, vitamina D e outros nutrientes.

A Simplified Protocol for Microsatellite Instability Evaluation in Iranian Patients at Risk for Lynch Syndrome.

OBJECTIVE: The most important tumor characteristic of Lynch syndrome (LS) is microsatellite instability (MSI). In the current study, BAT34c4 and BAT26 mononucleotide markers were evaluated as part of efforts to test a cost-effective panel for MSI testing in Iranian patients, comparing it with the Promega kit. METHODS: Amsterdam II clinical criteria were used to identify patients at risk for LS. The MSI status of these patients was determined using BAT34c4 and BAT26 markers, as well as the Promega kit. The results of both methods were compared, and the sensitivity and specificity of new short tandem repeat (STR) markers were estimated using statistical formulas. RESULTS: Of the 37 patients we studied who were at risk for LS, 27% showed MSI-high results, via the Promega kit. The same results were achieved for BAT34c4 and BAT26 separately. CONCLUSIONS: The novel 2-marker kit for MSI testing has similar accuracy as the Promega kit at a lower cost, due to fewer markers and a more economical labeling method.

WRN Germline Mutation Is the Likely Inherited Etiology of Various Cancer Types in One Iranian Family.

BACKGROUND: Familial cancers comprise a considerable distribution of colorectal cancers (CRCs), of which only about 5% occurs through well-established hereditary syndromes. It has been demonstrated that deleterious variants at the newly identified cancer-predisposing genes could describe the etiology of undefined familial cancers. METHODS: The present study aimed to identify the genetic etiology in a 32-year-old man with early onset familial CRC employing several molecular diagnostic techniques. DNA was extracted from tumoral and normal formalin-fixed-paraffin-embedded (FFPE) blocks, and microsatellite instability (MSI) was evaluated. Immunohistochemistry staining of MMR proteins was performed on tumoral FFPE blocks. Next-generation sequencing (NGS), multiplex ligation-dependent amplification (MLPA) assay, and Sanger sequencing were applied on the genomic DNA extracted from peripheral blood. Data analysis was performed using bioinformatics tools. Genetic variants interpretation was based on ACMG. RESULTS: MSI analysis indicated MSI-H phenotype, and IHC staining proved no expressions of MSH2 and MSH6 proteins. MLPA and NGS data showed no pathogenic variants in MMR genes. Further analysis of NGS data revealed a candidate WRN frameshift variant (p.R389Efs*3), which was validated with Sanger sequencing. The variant was interpreted as pathogenic since it met the criteria based on the ACMG guideline including very strong (PVS1), strong (PS3), and moderate (PM2). CONCLUSION: WRN is a DNA helicase participating in DNA repair pathways to sustain genomic stability. WRN deficient function may contribute to CRC development that is valuable for further investigation as a candidate gene in hereditary cancer syndrome diagnosis.

A randomized clinical trial of metacognitive therapy and nortriptyline for anxiety, depression, and difficulties in emotion regulation of patients with functional dyspepsia.

Functional Dyspepsia (FD) as a psychosomatic disorder is an upper gastrointestinal tract disease without organic pathogenesis causes. The psychopathological nature of this disease and its high correlation with anxiety and depression implies the need for psychological interventions. The purpose of the present study is to compare the efficacy of Metacognitive Therapy (MCT) and medication for the symptoms of anxiety, depression, and difficulties in emotion regulation in patients with FD. In a randomized clinical trial, 65 patients with FD were recruited during their visit to gastroenterology clinics. These patients were randomly assigned to three groups to receive MCT, nortriptyline treatment, and controls. They were treated for 10 weeks and followed up three months later. The instruments used in this study were Hamilton anxiety and Depression Rating Scale (HAM-A and HDRS) and difficulties in emotion regulation scale. The results were analyzed using repeated measure analysis by SPSS (19- IBM). Data analysis showed statistically significant differences in the variables of depression, anxiety among MCT, nortriptyline treatment, and controls at pre-test, post-test and follow-up phases. Moreover, MCT had a better and more persistent effect on anxiety compared to nortriptyline treatment, as well as a better efficacy in treating anxiety and depression symptoms compared to the controls. MCT demonstrated better efficacy in treating anxiety symptoms compared to nortriptyline treatment and controls.

Diagnostic value of alarm symptoms for upper GI malignancy in patients referred to GI clinic: A 7 years cross sectional study.

BACKGROUND: Early upper gastrointestinal (UGI) cancer detection had led to organ-preserving endoscopic therapy. Endoscopy is a suitable method of early diagnosis of UGI malignancies. In Iran, exclusion of malignancy is the most important indication for endoscopy. This study is designed to see whether using alarm symptoms can predict the risk of cancer in patients. MATERIALS AND METHODS: A total of 3414 patients referred to a tertiary gastrointestinal (GI) clinic in Isfahan, Iran, from 2009 to 2016 with dyspepsia, gastroesophageal reflux disease (GERD), and alarm symptoms, such as weight loss, dysphagia, GI bleeding, vomiting, positive familial history for cancer, and anorexia. Each patient had been underwent UGI endoscopy and patient data, including histology results, had been collected in the computer. We used logistic regression models to estimate the diagnostic accuracy of each alarm symptoms. RESULTS: A total of 3414 patients with alarm symptoms entered in this study, of whom 72 (2.1%) had an UGI malignancy. According to the logistic regression model, dysphagia (P < 0.001) and weight loss (P < 0.001) were found to be significant positive predictive factors for malignancy. Furthermore, males were in a significantly higher risk of developing UGI malignancy. Through receiver operating characteristic curve and the area under the curve (AUC) with adequate overall calibration and model fit measures, dysphagia and weight loss as a related cancer predictor had a high diagnostic accuracy (accuracy = 0. 72, AUC = 0. 881). Using a combination of age, alarm symptoms will lead to high positive predictive value for cancer. CONCLUSION: We recommend to do an early endoscopy for any patient with UGI symptoms and to take multiple biopsies from any rudeness or suspicious lesion, especially for male gender older than 50, dysphagia, or weight loss.

Relationship between articular and nonarticular manifestations in inflammatory bowel diseases.

BACKGROUND: Musculoskeletal manifestations (MSM) of inflammatory bowel diseases (IBDs) are usually the most frequent extraintestinal manifestations. However, they are not paid enough attention during regular office visits. This cross-sectional study aimed to draw a clinical picture of MSM and their relationships with other findings in patients with IBD. MATERIALS AND METHODS: Patients of our IBD cohort between March 2012 and September 2013 were consecutively evaluated. Those with current or past history of any MSM were examined by a rheumatologist. The outcome of interest was different MSMs. Distribution of IBD manifestations between the two groups of patients with (n = 20) and without (n = 253) MSM was compared. Logistic regression analysis was employed to find the relationships of demographic, clinical, and laboratory findings with MSM. RESULTS: Two hundred and seventy-three patients were enrolled. Forty-two patients (15.4%) had extraintestinal manifestations of which twenty patients (7.5%) had at least one MSM. 7/20 patients (35%) versus 22/253 (8.7%) had other extraintestinal manifestations (P = 0.0001). 12/20 patients (57%) had arthritis (polyarthritis, 33% and oligoarthritis, 67%). The most frequent involved joints were knee and ankle observed in 8 (40%) and 7 (35%) patients, respectively. The inflammatory back pain was recorded in 5/20 patients (25%) whereas two patients (10%) had ankylosing spondylitis. In regression analysis, oral aphthous (odds ratio [OR] =8.8 [95% confidence intervals (CI), 1.7-45], P = 0.009) and other extraintestinal manifestations (OR = 5.2 [95% CI, 1.3-20], P = 0.02) were significantly related with arthritis. CONCLUSION: The most frequent extraintestinal manifestations in patients with IBD were MSM. Knee and ankle were the most frequent involved joints. Extraintestinal manifestations were determinant variables of arthritis.

Adding diclofenac to Helicobacter pylori eradication regimen.

BACKGROUND: Helicobacter pylori colonizes not only on the surface of mucous membrane, but also beneath the surface mucous gel layer (SMGL). As diclofenac Na decreases the secretion of SMGL, in this study we examined this drug as an adjuvant therapy to a quadruple therapy for H. Pylori eradication. MATERIALS AND METHODS: One hundred and seventy-two patients were randomly assigned to three groups. Fifty four patients received quadruple therapy, that is, azithromycine 250 mg, amoxicillin 500 mg, bismuth subcitrate 240 mg, and omeprazole 20 mg bid for 1 week (group A) and 65 patients received the same dosage of those agents plus diclofenac Na tab, 100 mg daily for 1 week (group B). Sixty two patients received the quadruple therapy for 2 weeks (group C). Eradication of the infection was assessed 4-6 weeks after completion of treatment by stool antigen assay for H. pylori. RESULTS: While the rate of H. pylori eradication in the groups A and B was 66.7% and 82.1%, respectively (P = 0.062), the rate of H. pylori eradication in groups B and C were 82.1% and 82.3% respectively (P = 0.987). CONCLUSIONS: It seems that diclofenac Na can shorten anti-H. pylori regimens for 1 week. More investigations are needed for more clarification of the efficacy of NSAIDs for successful eradication of H. pylori. (IRCT code: IRCT201204059256N2).

Cancer problem in Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is a rare autosomal dominantly inherited condition, characterized by the presence of hamartomatous gastrointestinal polyps and mucocutaneous pigmentation. Patients with this syndrome can be associated with other neoplasms such as ovarian neoplasms known as sex-cord tumor with annular tubules that are associated in one third of the cases with this syndrome and other types of malignancies. We report a 42-year-old woman with a history of Peutz-Jeghers Syndrome and bilateral breast cancer that presented with abnormal uterine bleeding. Total abdominal hysterectomy with bilateral salpino-oophorectomy was done and an ovarian sex cord tumor with annular tubules was incidentally diagnosed. By reviewing literatures and in agreement with previous studies we suggest routine screening for malignancies in patients with Peutz-Jeghers syndrome.

Two novel mutations in hMLH1 gene in Iranian hereditary non-polyposis colorectal cancer patients.

Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common forms of hereditary colorectal cancer. It is an autosomal dominant disorder resulting from germline mutations in DNA mismatch repair genes. In this study, we screened hMLH1 gene in a group of Iranian HNPCC patients using polymerase chain reaction-single strand conformational polymorphism and direct sequencing methods. Here we report two novel frameshift mutations in this gene in our studied population. One of them results from a deletion of "T" at codon 36, exon 1 which causes premature stop codon and a truncated protein. The other results from a deletion of "T" at codon 753, exon 19 causing a delayed stop codon. There are a variety of the reported novel mutations in hMLH1 gene studies. Identification of these mutations is necessary in different populations and can help the management of colorectal cancer in these populations by screening, by prevention strategies, and by following up the suspected HNPCC families.

Cost-effectiveness analysis of colorectal cancer screening methods in Iran.

INTRODUCTION: Screening can prevent colorectal cancer from becoming advanced by early detection of precancerous lesions. Cost-effectiveness analysis of colorectal cancer screening methods is highly necessary due to increased prevalence, decreased age at onset and the limited budget in Iran. METHODS: Methods of screening currently available in Iran were selected. A systematic search revealed the sensitivity and specificity of each method. For this study, a model for a 20 year screening period of a population of 100,000 apparently healthy persons of ages 45-65 years in Isfahan Province was used. The cost-effectiveness of each method and the ratio of cost-effectiveness were calculated based on this model. RESULTS: The most and the least effective methods were CT colonography and fecal occult blood test, respectively. The highest and lowest expenditures in the governmental sector were related to fecal occult blood test and flexible sigmoidoscopy and in the private sector, to CT colonography and fecal occult blood test, respectively. The cost per cancer detected in 20 years of screening in the governmental sector was 0.28, 0.22 and 0.42 billion Rials, respectively for screening by colonoscopy, flexible sigmoidoscopy and fecal occult blood test. In the private sector, these were 1.54 (colonoscopy), 1.68 (flexible sigmoidoscopy), and 1.60 (fecal occult blood test) billion and 2.58 billion Rials for CT colonography, respectively. CONCLUSIONS: Although CT colonography is the most effective method, it needs a budget of 2.58 billion Rials for each screened patient. If costs in the governmental sector are considered, flexible sigmoidoscopy would be the most cost-effective method for screening the 45 - 65-year-old population in Iran.

Diagnostic values of Helicobacter pylori diagnostic tests: stool antigen test, urea breath test, rapid urease test, serology and histology.

BACKGROUND: The purpose of this study is to compare validity of 5 diagnostic tests of helicobacter pylori with each other: stool antigen test, urea breath test (UBT), rapid urease test (RUT), serology and histology. METHODS: A total of 94 patients who had indication of endoscopy entered the study. All of the 5 tests were performed for each patient. When the results of at least 2 tests were positive (except serology), Helicobacter pylori infection was considered to be positive. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under receiver operating characteristic (ROC) curve of these 5 tests were determined. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under ROC curve of these 5 tests are as below, respectively. HISTOLOGY: 89%, 78%, 93%, 91%, 85% and 0.881; RUT: 93%, 75%, 95%, 94%, 86% and 0.831; serology: 50%, 54%, 46%, 61%, 52% and 0.563; stool antigen test: 96%, 83%, 98%, 96%, 91% and 0.897; UBT: 89%, 73%, 92%, 90%, 82% and 0.892. CONCLUSIONS: Stool antigen test is the most accurate test for Helicobacter pylori diagnosis before eradication of these bacteria.

Diagnostic accuracy of IgA anti-tissue transglutaminase in patients suspected of having coeliac disease in Iran.

BACKGROUND AND AIM: As there are little data about the sensitivity of the IgA anti-tissue transglutaminase (IgA anti-tTG) antibody test in the clinical practice setting, we evaluated the sensitivity of this serologic test in a group of patients who were suspected of having coeliac disease and had serologic testing performed at commercial laboratories. PATIENTS AND METHODS: The study was performed at Poursina Hakim Research Institute in Isfahan-Iran. A total number of 350 consecutive patients were enrolled in our study. They were divided into 3 groups: classical mode of presentation, atypical mode of presentation and patients with non specific prolonged gastrointestinal symptoms. Upper gastrointestinal endoscopy, histopathologic examination of biopsies from the second part of duodenum and serologic evaluation were performed for every patient. Biopsy specimens were evaluated according to Marsh (1992, revised in 1997). RESULTS: The overall sensitivity and specificity of IgA anti-tTG antibody were 38% and 98%. The positive and negative predictive values for the anti-tTG antibodies were 57% and 96%, respectively. The sensitivity was 80% in patients with Marsh IIIC. CONCLUSION: In contrast to other reports suggesting a diagnostic accuracy of more than 90% for anti-tTG antibody in coeliac disease patients, our data showed that we are still far from an ideal screening serologic tool which can rely on the antibody test as the sole way of identifying patients with coeliac disease. This could result in many missed diagnoses, in particular in patients with lesser degrees of Marsh classification.

One-week versus two-week furazolidone-based quadruple therapy as the first-line treatment for Helicobacter pylori infection in Iran.

BACKGROUND AND AIM: Furazolidone-based regimens for the eradication of Helicobacter pylori are low cost and effective although less tolerable. Our aim was to compare the efficacy and compliance of 1-week furazolidone-based quadruple therapy (furazolidone, amoxicillin, bismuth subcitrate, omeprazole; FABO) with 2-week quadruple therapy using the same drugs. METHODS: One hundred and fifty-six consecutive patients with H. pylori related diseases were enrolled in our study. The patients were randomized into two groups of FABO1 and FABO2 groups receiving, 1 or 2 weeks' quadruple H. pylori eradication therapies, respectively, as follows: furazolidone (200 mg twice daily), amoxicillin (1 g twice daily), bismuth (240 mg twice daily) and omeprazole (20 mg twice daily). The chi(2) test was used to compare the efficacy of the therapies. RESULTS: The per-protocol eradication rate in FABO1 and FABO2 groups were 56/66 (84.8%) and 57/69 (82.6%), respectively. The intention-to-treat eradication rate was 56/78 (71.8%) in FABO1 group and 57/78 (73.1%) in FABO2 group. There was not any significant statistical difference between two groups. A significant decrease in compliance in FABO2 group was seen. CONCLUSION: This is an encouraging report showing a therapy with possible success in decreasing the duration of H. pylori infection as well as reaching the eradication rate of 80%.

Where does hypnotherapy stand in the management of irritable bowel syndrome? A systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause. Despite its prevalence, there remains a significant lack of efficient medical treatment for IBS to date. However, according to some previous research studies, hypnosis has been shown to be effective in the treatment of IBS. AIM: To determine the definite efficacy of hypnosis in the treatment of irritable bowel syndrome. METHODS: A systematic review of the literature on hypnosis in the treatment of IBS from 1970 to 2005 was performed using MEDLINE. Full studies published in English were identified and selected for inclusion. We excluded case studies and those studies in which IBS symptoms were not in the list of outcome measures. All studies were reviewed on the basis of the Rome Working Team recommendations for design of IBS trials. RESULTS: From a total of 22 studies, seven were excluded. The results of the reviewed studies showed improved status of all major symptoms of IBS, extracolonic symptoms, quality of life, anxiety, and depression. Furthermore these improvements lasted 2-5 years. CONCLUSIONS: Although there are some methodologic inadequacies, all studies show that hypnotherapy is highly effective for patients with refractory IBS, but definite efficacy of hypnosis in the treatment of IBS remains unclear due to lack of controlled trials supporting this finding.