Prevalence of functional dyspepsia-like symptoms in ulcerative colitis patients in clinical remission and overlap with irritable bowel syndrome-like symptoms.

Objective: Quiescent ulcerative colitis (UC) patients often have irritable bowel syndrome (IBS)-like symptoms and we recently showed that the prevalence of IBS-like symptoms in UC patients in clinical remission was significantly higher as compared to healthy control subjects. However, the prevalence of functional dyspepsia (FD)-like symptoms in quiescent UC patients remains unknown. The purpose of this study was to evaluate the prevalence of FD-like symptoms and the overlap with IBS-like symptoms in such patients.Materials and Methods: We reanalyzed the records of UC patients in remission using the subject cohort from our previous study. Clinical remission was defined as a clinical activity index (CAI) value ≤4 for at least 6 months. Diagnoses of FD- and IBS-like symptoms were evaluated by questionnaire according to the Rome III criteria.Results: One hundred seventy-two UC patients in clinical remission and 330 healthy control subjects were analyzed. Of the 172 patients, 9 (5.2%) met the criteria of FD, which was comparable with the controls (22/330, 6.7%). The prevalence rate of FD-like symptoms in UC patients with IBS-like symptoms (7/46, 15.2%) was lower as compared to that of the control subjects (6/16, 37.5%). On the other hand, a high percentage of the UC patients with FD-like symptoms also had IBS-like symptoms (7/9, 77.8%).Conclusions: Although the prevalence of FD-like symptoms in quiescent UC patients with IBS-like symptoms was low, UC patients with FD-like symptoms frequently had IBS-like symptoms.

Prospective multicenter study of the esophageal triamcinolone acetonide-filling method in patients with subcircumferential esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: The esophageal triamcinolone acetonide (TA)-filling method is a novel local approach for stenosis prevention after extensive esophageal endoscopic submucosal dissection (ESD). We evaluated this method after subcircumferential ESD. METHODS: We enrolled 20 patients with esophageal cancer requiring subcircumferential ESD in a prospective multicenter study. Esophageal TA filling was carried out 1 day and 1 week after ESD, with follow-up endoscopy every 2 weeks. We treated severe stenosis preventing endoscope passage with endoscopic balloon dilatation (EBD) and additional TA filling, and mild stenosis allowing endoscope passage with additional TA filling only. Primary endpoint was incidence of severe stenosis; secondary endpoints were total number of EBD, rate of additional TA filling, time to stenosis and complete re-epithelialization, dysphagia score, and adverse events. Horizontal resection grade was divided into grades 1 (≥ 9/12 and <10/12 of the circumference), 2 (≥ 10/12 and <11/12), and 3 (≥ 11/12 but not circumferential) and analyzed statistically for correlation with endpoints. RESULTS: Incidence of severe stenosis was 5.0% (1/20; 0.1-24.8%) and was treated with three EBD. Six patients showed mild stenosis. Additional TA filling was carried out in these seven patients: 0% (0/9) for grade 1 resection, 40% (2/5) for grade 2, and 83% (5/6) for grade 3 (P < 0.05). Median time to stenosis and re-epithelialization was 3 and 7 weeks, respectively. Dysphagia score deteriorated in one patient. No adverse events occurred. CONCLUSIONS: The esophageal TA-filling method prevented stenosis after subcircumferential ESD. Grade ≥2 resection showed a high risk for stenosis, but additional TA filling for mild stenosis inhibited stenosis progression (UMIN000024384).

Is Asymptomatic Esophageal Eosinophilia the Same Disease Entity as Eosinophilic Esophagitis?

Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder that is characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation.1,2 Its prevalence has been increasing rapidly in both Western and Asian countries. In Japan, most of the cases of esophageal eosinophilia (EE) are found in an upper endoscopy examination for gastric cancer screening performed during a comprehensive health check-up.3,4 Indeed, we frequently encounter patients with asymptomatic EE showing typical endoscopic findings, such as linear furrows, as well as histologic findings compatible with EoE. However, the current clinical guidelines for EoE diagnosis include symptoms related to esophageal dysfunction, thus patients without symptoms do not fulfill the diagnostic criteria.1,2 The clinical characteristics remain to be fully elucidated,5 thus we aimed to clarify clinical features of asymptomatic EE as compared with those of EoE.

Esophageal triamcinolone acetonide-filling method: a novel procedure to prevent stenosis after extensive esophageal endoscopic submucosal dissection (with videos).

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for extensive esophageal carcinomas may cause severe stenosis requiring endoscopic balloon dilations (EBDs). A standard prevention method has not been established. We propose the esophageal triamcinolone acetonide (TA)-filling method as a novel local steroid administration procedure. METHODS: We enrolled 22 consecutive patients with early esophageal cancer who were treated using either subcircumferential or circumferential ESD (15 and 7 procedures, respectively) in this case series. Esophageal TA filling was performed on the day after ESD and 1 week later and was performed again if mild stenosis was found on follow-up. EBD with TA filling was performed only for severe stenosis that prevented endoscope passage. The primary endpoint was the incidence of severe stenosis. Secondary endpoints were the total number of EBDs and additional TA filling, dysphagia score, time to stenosis and to complete re-epithelialization, and any adverse events. RESULTS: The incidence of severe stenosis was 4.5% (1/22; confidence interval, .1%-22.8%), and EBD was performed 2 times in 1 patient. Mild stenosis was found in 9 patients. Additional TA filling was performed in 45.5% of patients (10/22; median, 5 times; range, 1-13). The dysphagia score deteriorated to 1 to 2 in 31.8% (7/22) but showed a final score of 0 after complete re-epithelialization in 90.9% (20/22). The median time to stenosis was 3 weeks (range, 3-4) and that to complete re-epithelialization was 7 weeks (range, 4-36). No severe adverse events occurred. CONCLUSIONS: The esophageal TA-filling method is highly effective for preventing severe stenosis after extensive esophageal ESD.

Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett's esophagus.

Crosstalk between the Notch signaling pathway and Caudal-related homeobox 2 (Cdx2) has important roles in the development of Barrett's esophagus (BE). We investigated the expression and function of the Notch signaling ligand Delta-like 1 (Dll1) during the development of BE. We determined the expression levels of Dll1 and intracellular signaling molecules related to Notch signaling ((Notch1, Hairy/enhancer of split 1 (Hes1), and Atonal homolog 1 (ATOH1)) in human esophageal squamous and Barrett's epithelium samples. Next, those expression levels in esophageal squamous cells (Het-1A) and Barrett's esophageal cells (CP-A and BAR-T) following stimulation with either bile acids or gamma-secretase inhibitor were investigated. Finally, changes in those expression levels following transfection of a Cdx2 or Dll1 expression vector into Het-1A cells were examined. In addition, changes in those expression levels following knockdown of Cdx2 or Dll1 in CP-A cells were also examined. Dll1 was found to be upregulated and localized in the cell membrane and cytoplasm in BE. Bile acids enhanced cytoplasmic expression of Dll1 in CP-A cells, while cleaved Notch1 expression did not change, suggesting lack of a Dll1 agonistic effect on Notch signaling. Cells transfected with Cdx2 revealed significantly enhanced Dll1, while forced expression of Dll1 enhanced ATOH1, Cdx2, and MUC2 expression levels. Nevertheless, enhanced Dll1 did not induce Hes1 expression, suggesting that Dll1 may primarily function as an intracellular signaling molecule and not a Notch agonistic ligand in the canonical pathway. In addition, knockdown of Cdx2 completely abrogated any increase in Dll1 expression upon treatment with bile acids. Our results revealed a novel function of Dll1: facilitation of intestinal metaplasia in conjunction with Cdx2 expression. Furthermore, they suggest that intracellular induction of Dll1 expression in esophageal epithelial cells due to Cdx2 induction in response to bile acids has important roles in BE development.

Prevalence of gastroesophageal reflux disease in children, adults, and elderly in the same community.

BACKGROUND AND AIM: The prevalence of gastroesophageal reflux disease (GERD) in adults is increasing in Japan as well as worldwide likely due to increasing obesity and the decreasing rate of Helicobacter pylori infection. However, data regarding the prevalence of GERD in children and adolescents in Japan are lacking. We investigated the prevalence of GERD in children, adults, and elderly living in the same community. METHODS: We surveyed employees of Shimane University Hospital and a related facility and their families using the Gastroesophageal Reflux Disease Questionnaire (GerdQ) and Izumo Scale instruments with demographic information (age, sex, body height, and body weight) and information regarding concurrent medication being taken for GERD. The presence of GERD was defined as a GerdQ score of ≥ 8. RESULTS: A total of 1859 subjects (771 males, 1088 females; 6-96 years old) were eligible for assessment. The prevalence of GERD in those under 20 years old was 4.4%, which was approximately one third of the rate in adults (11.6%). GERD prevalence was closely associated with obesity in adults, but not in subjects under 20 years old. GERD and other gastrointestinal symptoms frequently overlapped in both adults and younger subjects. CONCLUSION: We found that the prevalence of GERD in subjects under 20 years of age was lower than that in adults and not associated with obesity. Nevertheless, it is important to be aware of symptoms such as heartburn and/or regurgitation when children and adolescents seek routine clinical care.

Notch signaling pathway and Cdx2 expression in the development of Barrett's esophagus.

Cdx2 expression in esophageal stem cells induced by reflux bile acids may be an important factor for development of Barrett's esophagus, whereas Notch signaling is a molecular signaling pathway that plays an important role in the determination of cell differentiation. ATOH1 (a factor associated with Notch signaling) plays an important role in differentiation of stem cells into goblet cells. However, the relationship between the Notch signaling pathway and Cdx2 expression in the development of Barrett's esophagus has not been explored. The aim of this study was to investigate the interrelationship between Notch signaling and Cdx2 in esophageal epithelial cells. The expressions of Cdx2, MUC2, and intracellular signaling molecules related to Notch signaling (Notch1, Hes1, and ATOH1) were examined using real-time polymerase chain reaction (PCR) and immunohistochemical staining with biopsy specimens obtained from esophageal intestinal metaplasia (IM) with goblet cells (IM⁺) and columnar epithelium not accompanied by goblet cells (IM⁻). For in vitro experiments, we employed human esophageal epithelial cell lines (OE33, OE19, and Het-1A). After forced Cdx2 expression by applying a Cdx2 expression vector to the cells, changes in the expressions of Notch1, Hes1, ATOH1, Cdx2, and MUC2 were analyzed by real-time PCR and western blot analysis. Changes in expressions of Notch1, Hes1, ATOH1, Cdx2, and MUC2 in cells were analyzed following stimulation with bile acids in the presence or absence of Cdx2 blocking with Cdx2-siRNA. Suppressed Hes1 and enhanced ATOH1 and MUC2 expressions were identified in IM⁺ specimens. Forced expression of Cdx2 in cells suppressed Hes1, and enhanced ATOH1 and MUC2 expressions, whereas bile acids suppressed Hes1, and enhanced ATOH1, Cdx2, and MUC2 expressions. On the other hand, these effects were blocked by siRNA-based Cdx2 downregulation. Enhanced expression of Cdx2 by stimulation with bile acids may induce intestinal differentiation of esophageal columnar cells by interaction with the Notch signaling pathway.

Fatty acid synthase expression in Barrett's esophagus: implications for carcinogenesis.

GOALS: To investigate the relationship between fatty acid synthase (FASN) expression and the clinicopathological characteristics of Barrett's esophagus and its carcinogenesis. BACKGROUND: FASN, a key enzyme of the fatty acid biosynthetic pathway, is overexpressed not only in various types of cancer, but also in premalignant conditions. Therefore, FASN overexpression is considered to be indicative of a possible premalignant stage. STUDY: Patients (N=354) with endoscopically and histologically proven Barrett's esophagus were enrolled. Mucin phenotyping of Barrett's esophagus, expression of FASN and COX-2, cellular proliferation, and apoptosis were evaluated immunohistochemically in biopsy samples, and factors influencing FASN expression were determined by multivariate logistic regression analysis. To evaluate if gastric reflux induces FASN expression, esophageal adenocarcinoma cells were treated with bile acid and low pH, and the effect of a FASN inhibitor on cell proliferation was assessed. RESULTS: Expression of FASN protein was observed in 52.2% of patients with Barrett's esophagus by immunohistochemistry; this expression pattern was retained in esophageal adenocarcinoma. Intestinal mucin phenotype, COX-2, increased stromal angiogenesis, and elevated proliferating cell nuclear antigen index were confirmed to be positive independent factors for FASN expression. In the esophageal adenocarcinoma cell line SEG-1, FASN mRNA was induced by bile acid with low pH. Cell proliferation was strongly suppressed by the FASN inhibitor C75. CONCLUSIONS: FASN is strongly expressed in the intestinal mucin phenotype of Barrett's esophagus, in which Barrett's glandular cells display elevated cellular proliferation, angiogenesis, and COX-2 expression. Exposure of the lower esophagus to bile acid with low pH may induce FASN in Barrett's esophagus.

[Points that should be considered for selecting drugs for the prevention and treatment of NSAIDs-related ulcers].

Many factors including past-history of ulcers, co-administration of glucocorticoid, and age of a case are important for selecting anti-ulcer medications to prevent the occurrence of gastro-duodenal ulcers during the administration of non-steroidal anti-inflammatory drugs (NSAIDs). In Japan, lansoprazole is a first line therapeutic drug for high risk patients with a past-history of ulcers, since lansoprazole is approved by the Japanese regulating agency to be administered to chromic NSAIDs users with a history of gastro-duodenal ulcers for preventing the recurrence of ulcers. Other high risk patients without ulcer history may be treated by the preventive administration of misoprostol. When misoprostol can not be used because of side effects etc, rebamipide and histamine-H2-recepter antagonists like famotidine are considered to be good options. For the treatment of NSAIDs-related gastro-duodenal ulcers, proton pump inhibitors or prostaglandins are selected if NSAIDs administration can not be interrupted. For the prevention and treatment of NSAIDs-related intestinal ulcers, the information we have is not clear enough for the appropriate drug selection.

Evaluations of Gastric Acid Pocket Using Novel Vertical 8-Channel pH Monitoring System and Effects of Acid Secretion Inhibitors.

BACKGROUND/AIMS: The gastric acid pocket has an important role in gastroesophageal reflux disease development. In this study, we utilized a novel 8-channel pH monitoring system with sensor intervals of 1 cm on the vertical axis for evaluation of postprandial gastric acid pocket in healthy Japanese adults, as well as the effects of vonoprazan and rabeprazole. METHODS: Twelve healthy volunteers without Helicobacter pylori infection were enrolled. A catheter was inserted transnasally and positioned under X-ray guidance, then postprandial acid pocket formation was monitored over time in a sitting position. Thereafter, acid pocket changes were assessed following administration of vonoprazan (20 mg) or rabeprazole (20 mg). RESULTS: The gastric acid pocket was successfully measured by use of the present system in 10 cases, while failure occurred in 2 because of inappropriate catheter positioning. Observed acid pockets were visualized with a mean length of 2.2 ± 0.4 channels on the top layer of food contents approximately 20 minutes after finishing a meal. There were some variations for lasting time of the acid pocket. Complete elimination within 3 hours after administration of vonoprazan was noted in all cases. Likewise, following administration of rabeprazole, the acid pocket was eliminated in 7 cases, while acidity was reduced though the pocket remained observable in 3. CONCLUSION: s Gastric acid pocket observations were possible using our novel vertical 8-channel sensor catheter. The present findings showed that vonoprazan strongly suppressed acid secretion within a short period, suggesting its effectiveness for gastroesophageal reflux disease treatment.

Magnification endoscopy in combination with acetic acid enhancement and narrow-band imaging for the accurate diagnosis of colonic neoplasms.

Background and study aims Magnification endoscopy with narrow-band imaging (NBIME) and NBIME with acetic acid enhancement (A-NBIME) enable visualization of the vascular and microstructural patterns of colorectal polyp. We compared the diagnostic accuracy and reproducibility of white light endoscopy (WLE), NBIME, and A-NBIME for predictive histologic diagnosis. Patients and methods Consecutive colorectal polyps (N = 628; 38 hyperplasias, 488 adenomas, 72 M-SM1 cancers, and 30 SM2 cancers) were photographed with WLE, NBIME, and A-NBIME. Endoscopic images were independently reviewed by three experts, according to the traditional criteria for WLE, the Japan NBI Expert Team classification for NBIME, and pit pattern classification for A-NBIME to compare diagnostic accuracy and interobserver diagnostic agreement among modalities. Results The specificity (95 % confidence interval) of hyperplasia and SM2 cancer with WLE were 98.2 % (96.8 %-99.1%) and 99.4 % (98.5 %-99.9 %), respectively, showing high accuracy for endoscopic resection without magnifying observation. Diagnostic accuracy of WLE, NBIME, and A-NBIME was 80.8 % (77.4 %-83.8 %), 79.3 % (75.9 %-82.4 %), and 86.1 % (83.2 %-88.7 %), respectively, showing the highest accuracy for A-NBIME among modalities ( P  < .05). NBIME showed a lower PPV for M-SM1 cancer ( P  < .05), as with WLE ( P  = .08) compared to A-NBIME. Fleiss's kappa values for WLE, NBIME, and A-NBIME diagnosis were 0.43 (0.39 - 0.46), 0.52 (0.49 - 0.56) and 0.65 (0.62 - 0.69), respectively, showing insufficient reproducibility of WLE and superiority of A-NBIME among modalities. Conclusion WLE showed high accuracy for endoscopic resection of colorectal polyps in expert diagnosis. NBIME demonstrated a higher diagnostic reproducibility than WLE. A-NBIME showed possible superiority among modalities in both diagnostic accuracy and reproducibility.

Ankylosaurus back sign: novel endoscopic finding in esophageal eosinophilia patients indicating proton pump inhibitor response.

BACKGROUND AND STUDY AIMS: Characteristic endoscopic findings, such as linear furrows, rings, and whitish exudates, indicate the presence of esophageal eosinophilia (EE), though no specific findings are known to distinguish eosinophilic esophagitis (EoE) from proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). Here, we present a novel endoscopic finding in some EE patients possessing a linear longitudinal arrangement of whitish nodules with the appearance of the back of an Ankylosaurus dinosaur, termed Ankylosaurus back sign (ABS), and evaluations of its significance in affected patients. PATIENTS AND METHODS: Fifty-five patients diagnosed with EE (≥ 15 eosinophils/high power field) who were treated at our hospital and shown to evaluate a PPI response were enrolled. Endoscopic findings at baseline and clinical parameters were retrospectively reviewed. Furthermore, the clinicopathological features of patients with ABS, as well as the relationship between its presence and PPI response were evaluated. RESULTS: Fifty-five patients (47 males, 8 females) with EE (17 with EoE, 38 with PPI-REE) were evaluated, of whom 50 (90.9 %) had linear furrows, the most frequently found feature, while ABS was found in 9 (16.4 %). Inter-observer agreement was substantial for ABS (κ 0.77). Interestingly, all patients with ABS had PPI-REE. Our findings revealed that the presence of ABS was closely associated with reflux esophagitis (RE) in patients with PPI-REE. CONCLUSIONS: Although ABS was less frequent than typical endoscopic findings such as linear furrows in EE, this novel finding was closely associated with PPI-REE accompanied with RE. The clinical implications of ABS in patients with EE should be investigated further.

Small Intestinal Bacterial Overgrowth in Patients with Refractory Functional Gastrointestinal Disorders.

BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) is considered to be involved in the pathogenesis of functional gastrointestinal disorders (FGID). However, the prevalence and clinical conditions of SIBO in patients with FGID remain to be fully elucidated. Here, we examined the frequency of SIBO in patients with refractory FGID. METHODS: We prospectively enrolled patients with refractory FGID based on Rome III criteria. A glucose hydrogen breath test (GHBT) was performed using a gas analyzer after an overnight fast, with breath hydrogen concentration measured at baseline and every 15 minutes after administration of glucose for a total of 3 hours. A peak hydrogen value ≥ 10 ppm above the basal value between 60 and 120 minutes after administration of glucose was diagnosed as SIBO. RESULTS: A total of 38 FGID patients, including 11 with functional dyspepsia (FD), 10 with irritable bowel syndrome (IBS), and 17 with overlapping with FD and IBS, were enrolled. Of those, 2 (5.3%) were diagnosed with SIBO (one patient diagnosed with FD; the other with overlapping FD and IBS). Their symptoms were clearly improved and breath hydrogen levels decreased to normal following levofloxacin administration for 7 days. CONCLUSIONS: Two patients initially diagnosed with FD and IBS were also diagnosed with SIBO as assessed by GHBT. Although the frequency of SIBO is low among patients with FGID, it may be important to be aware of SIBO as differential diagnosis when examining patients with refractory gastrointestinal symptoms, especially bloating, as a part of routine clinical care.

Simplified classification of capillary pattern in Barrett esophagus using magnifying endoscopy with narrow band imaging: implications for malignant potential and interobserver agreement.

The classification of Barrett esophagus (BE) using magnifying endoscopy with narrow band imaging (ME-NBI) is not widely used in clinical settings because of its complexity. To establish a new simplified available classification using ME-NBI.We conducted a cross-sectional study in a single-referral center. One hundred eight consecutive patients with BE using ME-NBI and crystal violet (CV) chromoendoscopy, and histological findings were enrolled. BE areas observed by ME-NBI were classified as type I or II on the basis of capillary pattern (CP), and as closed or open type on the basis of a mucosal pit pattern using CV chromoendoscopy; then, biopsy samples were obtained. We evaluated the relation between CP and pit pattern, expression of the factors with malignant potential, percentage of microvascular density, and interobserver agreement.One hundred thirty lesions from 91 patients were analyzed. Type II CP had more open type pit pattern areas and significantly greater microvascular density than type I. The presence of dysplasia, specialized intestinal metaplasia, expressions of COX-2, CDX2, and CD34, and PCNA index were significantly higher in type II, whereas the multivariate analysis showed that type II was the best predictor for the presence of dysplasia (OR 11.14), CD34 expression (OR 3.60), and PCNA (OR 3.29). Interobserver agreement for this classification was substantial (κ = 0.66).A simplified CP classification based on observation with ME-NBI is presented. Our results indicate that the classification may be useful for surveillance of BE with high malignant potential.

Crosstalk between TLR5 and Notch1 signaling in epithelial cells during intestinal inflammation.

During intestinal inflammation, a variety of signaling events are activated to perform several cell functions. Although the distinct roles of these pathways have been elucidated, the effects of their crosstalk activities remain to be clarified. We evaluated the crosstalk between two evolutionary conserved cell signaling systems, toll-like-receptor (TLR) 5 and Notch1, in intestinal epithelial cells during inflammation. Significant induction of the expression of Notch1 and Jagged1 was observed in the distal part of the colon, together with abundant localization of Notch1 intracellular domain (N1ICD) in the surface epithelium of inflamed colonic mucosa. By targeting intestinal epithelial cells, it was shown that recombination-signal-binding-protein-Jκ (RBP-Jκ)-mediated Notch functions are dependent on a flagellin-TLR5-mediated pathway. Conversely, using a γ-secretase inhibitor, we demonstrated that Notch synergistically increases TLR5­mediated NF-κB activation. In addition, the effects of Notch on the NF-κB target gene interleukin-6 (IL-6) expression were revealed by evaluating the RBP-Jκ responsive element in the IL-6 promoter in vitro. Modulation of TLR5 and Notch crosstalk by transient blocking of Notch during the acute phase of colitis was beneficial for ameliorating colonic inflammation as well as disease status. In conclusion, the results suggest the effectiveness of Notch-targeted drug strategy for the treatment of intestinal inflammation.

Impact of the composition of gastric reflux bile acids on Barrett's oesophagus.

BACKGROUND: The effect of the composition of reflux bile acids, especially the ratio of hydrophobic to hydrophilic ones, on the development of Barrett's oesophagus has not been fully investigated in human studies. AIMS: To evaluate the influence of the bile acid composition of gastric juice on Barrett's oesophagus, a prospective study was designed. METHODS: Fifty patients with and 100 patients without Barrett's oesophagus were enrolled. For all enrolled patients, gastric juice was collected by the endoscopic procedure for bile acid analysis. The ratio of hydrophobic to hydrophilic bile acids (bile hydrophobicity ratio, BHR) was calculated from 6 kinds of bile acids analysed in gastric juice. The relationship between the ratio and clinico-pathological factors of Barrett's oesophagus was investigated. RESULTS: The mean of BHR of patients with Barrett's oesophagus was significantly higher than that of patients without Barrett's oesophagus (0.26 ± 0.05 vs. 0.08 ± 0.02, p<0.05). In multivariate analysis, a high BHR value was a predictor for the presence of Barrett's oesophagus (OR 5.74, p<0.001). In patients with Barrett's oesophagus, the BHR correlated with COX-2 protein expression and with accelerated cellular proliferation. CONCLUSIONS: Patients with Barrett's oesophagus had a higher BHR in the gastric juice than those without.

A case of eosinophilic esophagitis with atypical clinical course.

Eosinophilic esophagitis is a rare chronic disease that mainly occurs in middle-aged males. Treatment with a glucocorticoid and/or proton pump inhibitor is usually necessary to relieve unpleasant symptoms. An 83-year-old female patient with dysphagia and heartburn was diagnosed with eosinophilic esophagitis based on endoscopic findings, while histological examination identified dense infiltration of intraepithelial eosinophils. The symptoms and eosinophil infiltration spontaneously disappeared without any treatment approximately 2 months later. No obvious lifestyle or dietary changes to explain elimination of possible antigens were identified in this case. We report an atypical case of eosinophilic esophagitis with spontaneous regression.

Administration of PPARß/δ agonist reduces copper-induced liver damage in mice: possible implications in clinical practice.

In this study we investigated if peroxisome proliferator-activated receptor ß/δ activation protects from copper-induced acute liver damage. Mice treated with copper had significant body weight loss, serum alanine aminotransferase increase, modest changes in liver histology, increase of tumor necrosis factor α and macrophage inflammatory protein 2 mRNA and 8-hydroxy-2'-deoxyguanosine. Mice treated with copper and peroxisome proliferator-activated receptor ß/δ agonist GW0742 had significantly less body weight loss, less serum alanine aminotransferase increase, less tumor necrosis factor α, macrophage inflammatory protein-2 and 8-hydroxy-2'-deoxyguanosine upregulation than copper treated mice. The opposite effect was observed in mice treated with copper and peroxisome proliferator-activated receptor ß/δ antagonist GSK0660. In vitro, copper induced reactive oxygen species, which was lower in cells treated with GW0742 or transfected with peroxisome proliferator-activated receptor ß/δ expression vector; together, transfection and GW0742 had an additive reactive oxygen species-reducing effect. Copper also upregulated Fas ligand and Caspase 3/7 activity, effects that were significantly lower in cells also treated with GW0742. In conclusion, peroxisome proliferator-activated receptor ß/δ activation reduced copper-induced reactive oxygen species, pro-inflammatory and acute phase reaction cytokines in mice liver. Peroxisome proliferator-activated receptor ß/δ agonists could become useful in the management of copper-induced liver damage.