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PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition.We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction.We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression.The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection.

BEST PRACTICE ADVICE 1: A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. BEST PRACTICE ADVICE 2: A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 3: Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett's esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 4: PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. BEST PRACTICE ADVICE 5: Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. BEST PRACTICE ADVICE 6: Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. BEST PRACTICE ADVICE 7: Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended.

The purpose of this review is to outline the recent developments in the field of extraesophageal reflux disease and provide clinically relevant recommendations. The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed and EMbase. The Clinical Practice Updates Committee of the American Gastroenterological Association proposes the following recommendations: Best Practice Advice 1: The role of a gastroenterologist in patients referred for evaluation of suspected extra esophageal symptom is to assess for gastroesophageal etiologies that could contribute to the presenting symptoms. Best Practice Advice 2: Non-GI evaluations by ENT, pulmonary and/or allergy are essential and often should be performed initially in most patients as the cause of the extraesophageal symptom is commonly multifactorial or not esophageal in origin. Best Practice Advice 3: Empiric therapy with aggressive acid suppression for 6-8 weeks with special focus on response of the extraesophageal symptoms can help in assessing association between reflux and extraesophageal symptoms. Best Practice Advice 4: No single testing methodology exists to definitively identify reflux as the etiology for the suspected extra esophageal symptoms. Best Practice Advice 5: Constellation of patient presentation, diagnostic test results and response to therapy should be employed in the determination of reflux as a possible etiology in extra esophageal symptoms. Best Practice Advice 6: Testing may need to be off or on proton pump inhibitor (PPI) therapy depending on patients' presenting demographics and symptoms in assessing the likelihood of abnormal gastroesophageal reflux. A. On therapy testing may be considered in those with high probability of baseline reflux (those with previous esophagitis, Barrett's esophagus or abnormal pH). B. Off therapy testing may be considered in those with low probability of baseline reflux with the goal of identifying moderate to severe reflux at baseline. Best Practice Advice 7: Lack of response to aggressive acid suppressive therapy combined with normal pH testing off therapy or impedance-pH testing on therapy significantly reduces the likelihood that reflux is a contributing etiology in presenting extraesophageal symptoms. Best Practice Advice 8: Surgical fundoplication is discouraged in those with extra esophageal reflux symptoms unresponsive to aggressive PPI therapy. Best Practice Advice 9: Fundoplication should only be considered in those with a mechanical defect (e.g., hiatal hernia), moderate to severe reflux at baseline off PPI therapy who have continued reflux despite PPI therapy and have failed more conservative non-GI treatments.

Points essentiels Si elle peut survenir a tout âge, l’œsophagite a eosinophiles doit etre evoquee principalement en cas de dysphagie et/ou impaction œsophagienne alimentaire chez un sujet jeune. Le diagnostic d’œsophagite a eosinophiles est suspecte sur des aspects endoscopiques et confirme par les biopsies œsophagiennes. Environ 50 % des œsophagites a eosinophiles repondent au traitement par inhibiteur de la pompe a protons. Le traitement de premiere intention repose sur les IPP et en cas d’echec sur les corticoides topiques ingeres dont les modalites de prise doivent etre clairement expliquees au patient. Un regime alimentaire d’exclusion des principaux allergenes alimentaires permet d’obtenir une remission clinique et histologique dans 75 % des cas environ. La reintroduction progressive des aliments permet d’identifier le ou les allergenes responsables. Les dilatations endoscopiques ne doivent etre proposees qu’en cas de stenose œsophagienne significative.

Background & Aims Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. Methods We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012. All study patients had undergone ileocolonic resection within 45 days before randomization. Patients were randomly assigned (1:1) to groups given infliximab (5 mg/kg) or placebo every 8 weeks for 200 weeks. The primary end point was clinical recurrence, defined as a composite outcome consisting of a CD Activity Index score >200 and a ≥70-point increase from baseline, and endoscopic recurrence (Rutgeerts score ≥i2, determined by a central reader) or development of a new or re-draining fistula or abscess, before or at week 76. Endoscopic recurrence was a major secondary end point. Results A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group, but this difference was not statistically significant (12.9% vs 20.0%; absolute risk reduction [ARR] with infliximab, 7.1%; 95% confidence interval: -1.3% to 15.5%; P =.097). A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group (30.6% vs 60.0%; ARR with infliximab, 29.4%; 95% confidence interval: 18.6% to 40.2%; P

Functional esophageal disorders consist of a disease category that present with esophageal symptoms (heartburn, chest pain, dysphagia, globus) not explained by mechanical obstruction (stricture, tumor, eosinophilic esophagitis), major motor disorders (achalasia, EGJ outflow obstruction, absent contractility, distal esophageal spasm, jackhammer esophagus), or gastroesophageal reflux disease (GERD). While mechanisms responsible are unclear, it is theorized that visceral hypersensitivity and hypervigilance play an important role in symptom generation, in the context of normal or borderline function. Treatments directed at improving borderline motor dysfunction or reducing reflux burden to sub-normal levels have limited success in symptom improvement. In contrast, strategies focused on modulating peripheral triggering and central perception are mechanistically viable and clinically meaningful. However, outcome data from these treatment options are limited. Future research needs to focus on understanding mechanisms underlying visceral hypersensitivity and hypervigilance so that appropriate targets and therapies can be developed.

Background & Aims Combined pH and impedance monitoring can detect all types of reflux episodes within the esophageal lumen and the pharynx. We performed a multicenter study to establish normal values of pharyngeal and esophageal pH-impedance monitoring in individuals on and off therapy and to determine the interobserver reproducibility of this technique. Methods We collected ambulatory 24-hour pH-impedance recordings from 46 healthy subjects by using a bifurcated probe that allowed for detection of reflux events in the distal and proximal esophagus and pharynx. Data were collected when subjects had not received any medicine (off therapy) and after receiving 40 mg esomeprazole twice daily for 14 days (on therapy). The interobserver agreement for the detection of reflux events was determined in 20 subjects off and on therapy. Results were expressed as median (interquartile range). Results Off therapy, subjects had a median of 32 reflux events (17–45) in the distal esophagus and 3 (1–6) in the proximal esophagus; they had none in the pharynx. On therapy, subjects had a median number of 21 reflux events (6–37) in the distal esophagus and 2 (0–5) in the proximal esophagus; again, there were none in the pharynx. Interobserver agreement was good for esophageal reflux events but poor for pharyngeal events. Conclusions We determined normal values of pharyngeal and gastroesophageal reflux events by 24-hour pH-impedance monitoring of subjects receiving or not receiving esomeprazole therapy. Analyses of esophageal events were reproducible, but analyses of pharyngeal events were not; this limitation should be taken into account in further studies. Eudract.ema.europa.eu, Number: 2010-022845-48.

Background & Aims Although methotrexate (MTX) is used in the effective treatment of inflammatory disorders, its use is hampered by the risk of liver fibrosis. Non-invasive methods for the diagnosis of liver fibrosis, such as transient elastography (FibroScan) and FibroTest could be useful for monitoring MTX–liver toxicity. The aim of this case–control study was to determine factors associated with liver fibrosis in a large cohort of patients requiring MTX. Methods Consecutive adults with various benign inflammatory diseases were prospectively assessed using FibroScan and FibroTest when they were treated with MTX (cases) or before beginning treatment (controls). Results Among 518 included patients, 44 patients (8.5%) had FibroScan and/or FibroTest results suggesting severe liver fibrosis. In a multivariate analysis, factors associated with abnormal markers of liver fibrosis were the body mass index >28kg/m2 and high alcohol consumption. Neither long MTX duration nor cumulative doses were associated with elevated FibroScan or FibroTest results. Conclusions Severe liver fibrosis is a rare event in patients treated with MTX and is probably unrelated to the total dose. Patients with other risk factors for liver disease should be closely monitored with non-invasive methods before and during MTX treatment.

Background & Aims Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associe aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. Methods We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Results Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03). Conclusions In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn's disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer.

Summary Objective The efficacy of intravenous cyclosporin (CSA) in acute severe ulcerative colitis (UC) is well established. The aim of this study was to evaluate its efficacy in moderately severe colitis refractory to steroids. Methods Twenty-six patients (17 men, mean age 41 ± 14 yr) with UC refractory to steroids treated with CSA were included in this study. Severity was defined according to Truelove criteria. A clinical activity score below 10 during 2 consecutive days defined clinical response. Results According to Truelove criteria, all patients had moderate UC. CSA was administered IV at a mean daily dose of 3.7 ± 0,5 mg/kg until response and then orally for 3.5 ± 2.6 months. A clinical response was achieved in 20/26 patients (76,9%) within 5.7 ± 2.8 days (5/6 failures were treated by proctocolectomy). During a follow-up of 27.8 ± 20.8 months, relapse rate was 60% (12/20): 7 patients underwent proctocolectomy and 5 had clinical remission with CSA retreatment (N = 4) and steroids (N = 1). At the end of follow-up, 12 patients (46%) were in clinical remission, 12 (46%) required colectomy, 1 had chronic active UC and 1 was lost of follow-up. The probability to avoid surgery was 52% at 78 months. The only factor associated with avoidance of surgery was concomitant treatment with azathioprine (P = 0.007). Ten reversible adverse events occurred in 9 patients. Conclusion This study shows that CSA is safe and effective in moderately severe steroid resistant UC. Concomitant treatment with azathioprine significantly decreases the rate of subsequent surgery. CSA may act as a “bridge” until the therapeutic action of azathioprine is achieved for maintenance treatment. These results should be further confirmed by a prospective controlled study.

NSAIDs-induced dyspepsia occurs in 10 to 30% of patients treated with NSAIDs, leading to discontinuation of treatment in 5 to 15%. Gastrointestinal tolerability of COX-2 selective inhibitors is better than for non-selective NSAIDs. Helicobacter pylori infection does not influence gastrointestinal tolerability of NSAIDs. Therefore, patients should not be tested and treated for H. pylori infection unless they have a history of peptic ulcer. Symptoms of NSAIDs-induced dyspepsia are poorly correlated with gastroduodenal mucosal damage. Therefore, upper gastrointestinal endoscopy should be performed only if symptom relief is not achieved with the first line empirical treatment and/or if symptoms suggestive of complications, such as bleeding, develop. Proton pump inhibitors appear to be the treatment of choice for NSAIDs-induced dyspepsia.

Resume But : Les adenocarcinomes de la jonction anorectale, en particulier les lesions T3, sont habituellement traites par une amputation abdominoperineale. Le but de cette etude etait d’evaluer les resultats oncologiques et fonctionnels apres traitement radiochirurgical conservateur de cancers de la jonction anorectale. Methodes : De 1990 a 1999, parmi 395 patients operes d’un cancer du rectum, 31 ont eu une chirurgie conservatrice pour une tumeur situee entre 2 et 4,5 cm (moyenne : 3,6) de la marge anale. Il y avait 16 hommes et 15 femmes, d’âge moyen 62 ans (extremes : 30–86). Les lesions etaient reparties de la facon suivante : 5 T2, 23 T3 et 3 T4 ; 17 etaient N1 et 3 M1. Une radiotherapie preoperatoire a ete realisee chez 26 patients (dose 46 Gy, extremes : 36–54), en association avec une chimiotherapie concomitante dans 14 cas. Six semaines plus tard, une resection rectale etait realisee, enlevant une partie ou la totalite du sphincter interne. Les anastomoses colo-anales etaient associees a un reservoir colique en J dans 22 cas et a une stomie de protection dans tous les cas. Resultats : Il n’y a pas eu de mortalite postoperatoire. Sept complications sont survenues : trois fistules anastomotiques, trois hemorragies pelviennes, une pancreatite aigue. Trois patients ont garde une stomie definitive. Apres radiotherapie, un down staging (pT0-2 N0) a ete observe dans 46 % des cas (12/26). La marge de resection distale etait de 2,2 cm (extremes : 1–3) microscopiquement saine dans tous les cas. La marge de resection laterale etait non envahie (⩾1 mm) dans 97 % des cas. Avec un recul de 36 mois, aucune recidive locale n’a ete suspectee. Vingt-six patients (84 %) etaient vivants, 23 sans recidive. La moitie des patients avaient une continence normale, l’autre moitie des fuites mineures occasionnelles. Les resultats fonctionnels etaient meilleurs avec un reservoir colique. Conclusion : Le traitement conservateur des adenocarcinomes de la jonction anorectale est possible sans compromettre le controle pelvien et la survie des patients. La radiotherapie preoperatoire et la resection intersphincterienne ont permis d’obtenir des marges de resection distales et laterales saines.

Porto, Portugal, 8University of Porto, 8 MedInUP Center for Drug Discovery and Innovative Medicines, Porto, Portugal, 9University of Medicine ←Victor Babes→, Clinic of Gastroenterology, Timisoara, Romania, 10Complexo Hospitalario Universitario de Vigo, Gastroenterology Department, Vigo, Spain, 11St Vincent's Hospital, Department of Gastroenterology, Melbourne, Victoria, Australia, 12Herlev University Hospital, Digestive Disease Center, Medical Section, Copenhagen, Denmark Background: The ECCO-EpiCom study investigates the differences in the incidence, disease characteristics and therapeutical management of inflammatory bowel diseases (IBD) between Eastern and Western Europe. The aim of this study was to analyze the differences in the therapeutical strategy in the 2011 ECCO-EpiCom inception cohort within the first year after diagnosis. Methods: Fourteen European (9 Western and 5 Eastern European centers) and one Australian center with 258 CD, 380 UC and 71 IBDU patients (65% from Western, 25% from Eastern Europe, 10% from Australia; female/male: 326/383; mean age at diagnosis: 40.9 years, SD: 17.3 years) participated in the one-year followup. Patients' data regarding disease characteristics and medical therapy were registered and entered in the web-based ECCOEpiCom database every third month during the first 12 months after diagnosis. Results: Both in CD and UC, a significant difference was found in the probability of highest treatment steps reached within one year after diagnosis between Eastern and Western Europe and Australia (Figure 1. and 2.). Overall, the disease behavior (B2 and B3) was the driver for immunosuppressive (IS) therapy (pLogRank

was assayed by immunoprecipitation and western blotting. To further investigate if PAR2 activation sensitized acid-induced ATP release through TRPV1 and ASICs, pretreatment with IRTX or amiloride for 45 min before trypsin (4 mg/ml, 60 min) was administered. Results: Acid stimulated the release of ATP from HEEC (217 ± 58 % Control, P

Background: Esophageal epithelial integrity is considered an important factor in the prevention of tissue damage by gastric refluxate.We hypothesized that in patients with gastroesophageal reflux disease (GERD) the esophageal epithelial barrier function is impaired and less resistant in response to acid exposure. We therefore investigated esophageal epithelial integrity in GERD patients and in healthy controls both in the basal state and in response to acid exposure Methods: 14 patients with chronic GERD (8 with erosive esophagitis, 6 with non-erosive reflux disease) and 10 healthy controls (HC) were enrolled. Before endoscopy, GERD patients discontinued PPI therapy for 7 days. Six esophageal biopsies frommacroscopically normal mucosa were obtained approximately 5 cm above the gastroesophageal junction and directly transferred to a mini-Ussing chamber system. After an equilibration period, baseline TEER was assessed. Half of the biopsies were then exposed at their luminal side to an acidic solution (pH1) for 30 minutes. During exposure and after removal of the acidic solution, changes in TEER were analyzed relative to baseline TEER. Permeation to the paracellular permeation marker fluorescein (375 DA 1 mg/ml) was assessed in all biopsies (previous acid-exposed and non-exposed) for 120 minutes. Only subjects with at least two adequate biopsies (one for acid exposure, one as a control) were included. Results: Esophageal epithelium of GERD patients showed lower baseline TEER (127.7±13.3 Ω vs. 174.3±17.6 Ω, p=0.04) and a trend toward higher transmucosal permeation of fluorescein in the nonexposed biopsies when compared to healthy controls (serosal concentration (pmol/ml) after 120 min: 48.2 (7.6-66.7) vs. 6.8 (3.6-20.2), p=0.09 and AUC: 79.8 (12.9-135.6) vs. 9.0 (5.5-31.3), p=0.07). Acid exposure provoked a fall in TEER that was equal for the biopsies of GERD patients and healthy controls (-52.1±2.5% vs. -50.0±4.4% of baseline TEER). After removal of the acidic solution, TEER recovered also to a similar extent in GERD patients and healthy controls (89.6±3.8% vs. 93.8±3.0% of baseline TEER). However, maximum TEER was reached earlier in biopsies of GERD patients (54±9 min vs. 83±6 min (HC), p= 0.02) and at the end of the experiment, TEER relative to baseline was lower in biopsies of GERD patients (73.7±5.8% vs. 89.7±3.3% (HC) of baseline TEER, p

Background: The natural history of CD of the pouch has not been characterized. Methods: All eligible patients with CD of the pouch were identified and included from our subspecialty Pouchitis Clinic between 2002 and 2009. Demographic & clinical variables were collected from a prospectively maintained database. Results: 206 pts with CD of the pouch consisted of 49 inflammatory, 40 fibrostenotic, and 117 fistulizing types. Pts with fistulizing CD were younger than those with fibrostenotic CD. The interval from IBD diagnosis and pouch construction was shorter in the fistulizing CD group. More pts with fistulizing CD had postoperative use of biologics (25.6% vs. 10.2% and 12.5%, p=0.028). More patients with fistulizing CD were hospitalized for pouch-related condition (21.4% vs. 15.0% and 2.0%, p=0.007). Progression of phenotypes and pouch survival are shown in Figures. Conclusions: Clinical phenotypes of Crohn's pouch can change over time. These phenotypes of CD were associated with different natural history and risk for pouch failure.

BACKGROUND: In patients with proton pump inhibitors (PPI) resistant reflux symptoms, ambulatory 24-hour pH-impedance monitoring can be used to assess whether a relationship exists between symptoms and reflux episodes. Using this technique we aimed to distinguish patients with hypersensitive esophagus and evaluate the effect of selective serotonin reuptake inhibitors (SSRI) on their symptoms. METHODS: Patients with normal endoscopy and typical reflux symptoms (heartburn, chest pain, regurgitation), despite PPI twice daily, underwent ambulatory 24-hour pH-impedance monitoring. Distal esophageal acid exposure (% time pH < 4) was measured. Reflux episodes were detected by impedance channels located 3, 5, 7, 9, 15 and 17cm above the lower esophageal sphincter (LES) and classified into acid or non-acid based on pH data from 5cm above the LES. A positive symptom index (SI) was declared if at least half of each specific symptom events were preceded by reflux episodes within five minutes. Patients with a normal distal esophageal acid exposure time, but with a positive symptom index for either acid and/or non acid reflux were classified as having hypersensitive esophagus and were randomized to receive citalopram 20mg or placebo once daily for 6 months. Data were analyzed using Fischer's exact test. RESULTS: A total of 84 patients (50 females (59.5%) and 34 males (40.5%); mean age 55 (range 18-75) years) with reflux symptoms despite taking PPI twice daily underwent 24-hour pH-impedance monitoring. Seventy three patients (86.9%) recorded symptoms during the study day, while 35 (47.9%) of those had a positive symptom index for at least one symptom (8 (22.9%) with acid and 27 (77.1%) with non acid reflux). Among those 35 patients, 25 (71.4%) had normal distal esophageal acid exposure time (i.e. hypersensitive esophagus) and were randomized to receive citalopram 20mg (group A, n=13) or placebo (group B, n=12) once daily for a period of 6 months. At the end of the follow up period, 3 out of the 13 patients of group A (23%) and 8 out of the 12 patients of group B (67%) continue to report reflux symptoms (p=0.047). CONCLUSIONS: Treatment with selective serotonin reuptake inhibitors is effective for patients with hypersensitive esophagus as defined by the use of 24-hour pH-impedance monitoring.