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.

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.

Circumferential distribution and location of Mallory-Weiss tears: recent trends.

BACKGROUND AND STUDY AIMS: Mallory-Weiss tears (MWTs) are not only a common cause of acute nonvariceal gastrointestinal bleeding but also an iatrogenic adverse event related to endoscopic procedures. However, changes in the clinical characteristics and endoscopic features of MWTs over the past decade have not been reported. The aim of this study was to investigate recent trends in the etiology and endoscopic features of MWTs. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with a diagnosis of MWT at our university hospital between August 2003 and September 2013. The information regarding etiology, clinical parameters, endoscopic findings, therapeutic interventions, and outcome was reviewed. RESULTS: A total of 190 patients with MWTs were evaluated. More than half (n = 100) of the cases occurred during endoscopic procedures; cases related to alcohol consumption were less frequent (n = 13). MWTs were most frequently located in the lesser curvature of the stomach and right lateral wall (2 - to 4-o'clock position) of the esophagus, irrespective of the cause. The condition of more than 90 % of the patients (n = 179) was improved by conservative or endoscopic treatment, whereas 11 patients (5.8 %) required blood transfusion. Risk factors for blood transfusion were a longer laceration (odds ratio [OR] 2.3) and a location extending from the esophagus to the stomach (OR 5.3). CONCLUSIONS: MWTs were frequently found on the right lateral wall (2 - to 4-o'clock position) of the esophagus aligned with the lesser curvature of the stomach, irrespective of etiology. Longer lacerations extending from the esophagus to the gastric cardia were associated with an elevated risk for bleeding and requirement for blood transfusion.

Effects of acotiamide on esophageal motor function and gastroesophageal reflux in healthy volunteers.

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide, with proton pump inhibitor (PPI) administration the current mainstay therapy for affected individuals. However, PPI efficacy is insufficient especially for non-erosive reflux disease. Although it has been reported that prokinetic drugs improve GERD, their effects on esophageal function remain to be clearly investigated. In the present study, we evaluated the direct effects of acotiamide, a novel prokinetic agent for the treatment of functional dyspepsia, on esophageal motor function and gastroesophageal reflux. METHODS: Ten adult healthy volunteers (average age 24 years, range 20-36 years; 7 males, 3 females) were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure with and without acotiamide administration were recorded using high resolution manometry using a cross-over protocol. Total and acidic reflux levels for 24 h and during the postprandial period were also recorded using a multichannel intraluminal impedance and pH monitoring system. Data were analyzed blind by one observer. RESULTS: Acotiamide at a standard dose of 300 mg/day did not significantly stimulate esophageal motor function. Although the frequency of swallows with weak contraction tended to decrease with acotiamide administration, the difference as compared to no administration was not statistically significant. In addition, the drug neither decreased total or postprandial gastroesophageal acid/non-acid reflux events nor accelerated esophageal clearance time. CONCLUSIONS: Acotiamide, a novel gastrointestinal motility modulator, at a standard dose did not significantly affect esophageal motor functions or gastroesophageal reflux in healthy adults. Additional investigations with GERD patients are necessary to elucidate its clinical significance. TRIAL REGISTRATION: This study was registered on 1st August 2013 with the University Hospital Medical Information Network (UMIN) clinical trials registry, as number: UMIN000011260.

Clinical features of eosinophilic esophagitis: differences between Asian and Western populations.

The prevalence and incidence of eosinophilic esophagitis (EoE) have been rapidly increasing in Western countries. It is thought to be more common among Caucasians than other racial or ethnic groups, but epidemiological studies have not been fully evaluated in Asian populations, and its clinical manifestation is rarely documented. In this review, recent reports regarding EoE in Asian countries have been collected, and differences in the clinical features, including symptoms and endoscopic findings, between Asian and Western populations have been evaluated. In Asia, EoE is still much less prevalent than in Western countries. Baseline values for average age, male/female ratio, and personal history of allergic disease were comparable to those in Western populations. Predominant symptoms were dysphagia, and food impaction was extremely rare among Asian patients. Although the frequency of abnormal endoscopic findings varies among studies, over 90% of patients with EoE have shown abnormal findings such as linear furrow, which is the most common findings, in recent prospective studies in Asia. There are few reports regarding the treatment of EoE and no prospective studies evaluating drugs or elimination diet in patient with EoE have been reported in Asia. Overall, EoE had similar clinical characteristics in Asian populations. Because the incidence of EoE could increase in the future with the increase in allergic disorders in Asian countries, large-scale, nationwide prospective studies should be performed to more fully understand the epidemiology and pathophysiology of EoE in Asian populations.

Novel stenting method for malignant right colonic stenosis using ultra-thin endoscopy: Report of four cases.

Placement of a self-expandable metallic stent (SEMS) is recognized as a safe and effective procedure for patients with malignant severe colonic stenosis. However, reports of this stent for right-sided colonic stenosis are limited, possibly as a result of technical difficulties. We report a new method for delivering SEMS to the site of right-sided colonic stenosis in four patients with malignant right-sided colonic stenosis. Technical success was obtained with sequential use of a double-balloon endoscope and ultrathin endoscope, while we also injected non-ionic contrast agent into the submucosal layer as a marker for stenting under fluoroscopy. There were no adverse events noted during the procedure and clinical improvement was seen in all four cases. In conclusion, SEMS placement for right-sided malignant colonic stenosis with our newly developed method appears to be safe and effective, and can be used for decompression of the right colon.

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.

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.

Effects of Daikenchuto on Abdominal Bloating Accompanied by Chronic Constipation: A Prospective, Single-Center Randomized Open Trial.

BACKGROUND: Daikenchuto (DKT), a traditional Japanese herbal medicine, is widely used for treatment of gastrointestinal disorders. We evaluated the efficacy and safety of DKT for abdominal bloating in patients with chronic constipation. OBJECTIVE: To evaluate the efficacy and safety of DKT for the treatment of abdominal bloating. METHODS: After discontinuing as-needed use of laxatives, 10 patients received oral DKT for 14 days (15 g/d). To evaluate small intestinal bacteria overgrowth (SIBO), a glucose breath test was performed before and after treatment with DKT. Before beginning the treatment, 4 patients (40%) had a diagnosis of SIBO based on a positive glucose breath test result. In both the SIBO and non-SIBO groups, bowel movement frequency and stool form remained unchanged after DKT treatment. RESULTS: For all patients, median total Gastrointestinal Symptoms Rating Scale score and the median Gastrointestinal Symptoms Rating Scale indigestion and constipation subscales were significantly decreased, whereas the median visual analog score for decreased abdominal bloating was significantly increased. Improvements of those symptoms were the same in both the SIBO and non-SIBO groups, indicating that DKT does not have effects on small intestine bacteria. No serious side effects were reported. CONCLUSIONS: DKT treatment improved quality of life for patients with chronic constipation regardless of the presence of SIBO and showed no effects on small intestine bacteria. UMIN Clinical Trial Registry identifier: UMIN000008070.

Pathophysiology of Barrett's esophagus-associated neoplasia: circumferential spatial predilection.

The prevalence rates of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) arising from BE show striking geographic patterns as they are much more common in Western as compared with Asian countries. However, recent epidemiological studies indicate that the number of patients with BE and EAC are gradually increasing in Asia including Japan, corresponding to the increase in prevalence of gastroesophageal reflux disease (GERD). Because the prognosis of patients with advanced-stage EAC remains poor, early detection of neoplastic lesion in those with BE has led to recent interest in effective treatment. Several promising studies have revealed that early neoplasia in BE is mainly located in the right anterior wall of the distal esophagus. Interestingly, this endoscopic characteristic has been found in both Western and Japanese populations. Potential pathophysiologic explanations underlying the circumferential distribution of neoplasia in BE include a nonuniform asymmetric distribution of esophageal acid exposure, with a tendency toward mucosal acid-related injury on the right side of the esophageal wall in patients with GERD, and the functional structure of the lower esophageal sphincter. Findings of the present study should improve lesion detection and aid in developing a target biopsy protocol for surveillance of BE.

Effects of mosapride on esophageal motor activity and esophagogastric junction compliance in healthy volunteers.

BACKGROUND: The effects of the prokinetic drug mosapride on esophageal motor activity vary at standard doses. In addition to esophageal motor activities, compliance of the esophagogastric junction (EGJ) is important for prevention of gastroesophageal reflux. However, the effects of mosapride on EGJ compliance have not been reported. Here, we investigated the effects of high-dose mosapride on esophageal motor activities and EGJ compliance. METHODS: Nine healthy volunteers were enrolled in the study. Peristaltic esophageal contraction and lower esophageal sphincter pressures before and after administration of 40 mg mosapride were examined by high resolution esophageal manometry. Esophageal compliance was also investigated by intra-esophageal impedance planimetry (EndoFLIP(®)). RESULTS: High-dose mosapride augmented peristaltic contractions, especially in the distal esophageal segments (P < 0.05). The mean resting lower esophageal sphincter pressure was elevated from 25.0 mmHg before administration to 28.9 mmHg after (P < 0.05). In addition, mosapride significantly reduced EGJ compliance (P < 0.05). CONCLUSIONS: Mosapride at 40 mg augmented esophageal motor activities and reduced EGJ compliance in healthy volunteers.

Influence of Full-body Water Immersion on Esophageal Motor Function and Intragastric Pressure.

BACKGROUND/AIMS: In Japan, it is customary to take a daily bath during which the body is immersed in water to the neck. During full-body immersion, hydrostatic pressure is thought to compress the chest and abdomen, which might influence esophageal motor function and intra-gastric pressure. However, whether water immersion has a significant influence on esophageal motor function or intragastric pressure has not been shown. The aim of this study was to clarify the influence of full-body water immersion on esophageal motor function and intragastric pressure. METHODS: Nine healthy male volunteers (mean age 40.1 ± 2.8 years) were enrolled in this study. Esophageal motor function and intragastric pressure were investigated using a high-resolution 36-channel manometry device. RESULTS: All subjects completed the study protocol. Intragastric pressure increased significantly from 4.2 ± 1.1 to 20.6 ± 1.4 mmHg with full-body water immersion, while the lower esophageal high pressure zone (LEHPZ) value also increased from 20.5 ± 2.2 to 40.4 ± 3.6 mmHg, with the latter being observed regardless of dietary condition. In addition, peak esophageal peristaltic pressure was higher when immersed as compared to standing out of water. CONCLUSIONS: Esophageal motor function and intragastric pressure were altered by full-body water immersion. Furthermore, the pressure gradient between LEHPZ and intragastric pressures was maintained at a high level, and esophageal peristaltic pressure was elevated with immersion.

Endoscopic characteristics of short-segment Barrett's esophagus, focusing on squamous islands and mucosal folds.

BACKGROUND AND AIM: Endoscopic definitions of Barrett's esophagus (BE) vary among countries, mainly because of the difficulty in diagnosing short-segment BE (SSBE) endoscopically. The aim of this study was to investigate whether the endoscopic identification of squamous islands and the specific position of columnar epithelium helps improve the diagnosis of SSBE. METHODS: First, we prospectively enrolled 100 consecutive patients with SSBE and evaluated the number of identified squamous islands in the columnar epithelium with different modalities: white light (WL), narrow band imaging (NBI), and iodine chromoendoscopy. Second, in another group of 100 consecutive patients with tongue-like SSBE, the correlation of the location of Barrett's mucosa to the esophageal longitudinal folds (ridge or valley) was evaluated endoscopically. RESULTS: It was possible to detect squamous islands in 48, 71, and 75 patients by WL, NBI, and iodine chromoendoscopy, respectively. The detection rate of squamous islands by NBI or iodine chromoendoscopy was significantly superior to that by WL. Tongue-like SSBEs were predominantly found on the ridge of mucosal folds (71%), similar to the location of mucosal breaks (84%). CONCLUSIONS: Squamous islands in the columnar epithelium were efficiently observed by NBI or iodine chromoendoscopy. SSBE was found more frequently on the ridges but not in the valleys of esophageal longitudinal mucosal folds. NBI endoscopic observation focusing on columnar epithelium with squamous islands on the ridges of distal esophageal folds may improve endoscopic detection of SSBE.

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.

Capnographic monitoring for carbon dioxide insufflation during endoscopic submucosal dissection: comparison of transcutaneous and end-tidal capnometers [corrected].

BACKGROUND: The use of carbon dioxide (CO(2)) insufflation during endoscopic procedures is effective in reducing patient discomfort caused by bloating. However, transcutaneous arterial CO(2) (PtCO(2)) monitoring usually is required for safety during long endoscopic procedures. To evaluate a new capnometer for monitoring end-tidal carbon dioxide (EtCO(2)) concentrations and to compare PtCO(2) with EtCO(2) measured in the same patient, a prospective comparative study of EtCO(2) and PtCO(2) values measured simultaneously was designed. METHODS: The study enrolled 20 consecutive patients (18 men and two women; mean age, 70.1 years) with upper gastrointestinal neoplasms scheduled for endoscopic submucosal dissection (ESD) using conscious sedation with CO(2) insufflation, and EtCO(2) and PtCO(2) were simultaneously measured by each capnometer. Patient status was evaluated before ESD by the American Society of Anesthesiologists (ASA) physical status classification system, and eight patients were judged as class 1, nine patients as class 2, and three patients as class 3. The exclusion criteria ruled out patients with chronic obstructive pulmonary disease or ASA class 4 or 5 physical status. The correlation between EtCO(2) and PtCO(2) values and the availability of EtCO(2) capnography were investigated. RESULTS: The mean EtCO(2) value during ESD was 34.7 ± 4.5 mmHg, and the mean PtCO(2) value was 51.6 ± 2.4 mmHg. There was a statistically significant correlation between EtCO(2) and PtCO(2) (r = 0.331; P = 0.002). Hypoxic events (<90% oxygen saturation [SpO(2)]) caused by decreased respiratory rate occurred for 12 patients. In 10 (83%) of 12 events, a significant reduction in EtCO(2) was seen before the decrease in SpO(2). CONCLUSIONS: The EtCO(2) values correlated with the PtCO(2) values, and the respiratory monitoring methods allowed earlier detection of hypoxia during ESD with conscious sedation than transcutaneous monitoring. The EtCO(2) capnometer was considered to be available for the ESD procedure with the patient under conscious sedation using CO(2) insufflation.

Relationship between kyphosis and Barrett's esophagus in Japanese patients.

BACKGROUND: Kyphosis is a risk factor for the presence of hiatal hernia, which is a strong predictor of Barrett's esophagus. However, the association between kyphosis and Barrett's esophagus has not yet been clarified. To investigate this relationship, the Cobb angle, a marker of kyphosis, was measured in patients with and without Barrett's esophagus. METHODS: From January 2006 to December 2010, 26 patients with long-segment Barrett's esophagus (LSBE) were retrospectively enrolled. As the comparative groups, 100 consecutive patients with short-segment Barrett's esophagus (SSBE) and 100 consecutive control patients without Barrett's esophagus were also enrolled in this study. Cobb angles were measured on lateral chest radiographs, and kyphosis was defined as a Cobb angle of greater than 50°. Kyphosis, along with other patient characteristics, were evaluated as possible predictors for SSBE and LSBE. RESULTS: The mean Cobb angles in the non-BE, SSBE, and LSBE groups were 31.6° (95% CIs, 29.3°-33.9°), 34.8° (32.1°-37.4°) and 49.4° (44.9°-53.9°), respectively. Statistically significant differences were found between the LSBE and the other 2 groups (p<0.001). The mean Cobb angles were 33.3°±12.4° and 37.0°±14.1°, respectively in patients without and with hiatal hernia (p=0.039). Predictors for Barrett's esophagus of any length were erosive esophagitis and hiatal hernia. Kyphosis had the highest odds ratio for the presence of LSBE (OR, 1.50; 95% CI, 1.05-1.94; p=0.033). Other predictors were hiatal hernia and the absence of Helicobacter pylori infection. CONCLUSION: Kyphosis is a risk factor for the presence of LSBE in Japanese patients.

Interobserver variation in the endoscopic diagnosis of gastroduodenal ulcer scars: implications for clinical management of NSAIDs users.

BACKGROUND: A clinical history of peptic ulcer has been reported to be associated with a high rate of ulcer recurrence in nonsteroidal anti-inflammatory drug (NSAID) users. Therefore, it is a very important issue to precisely know the previous history prior to NSAIDs administration. To clarify the possible difficulty to identify the history, we determined the sensitivity and diagnostic concordance of endoscopy for the identification of ulcer scars indicative of previous clinical history of peptic ulcer diseases. METHODS: The first study enrolled 200 consecutive patients with a clinical history of gastric or duodenal ulcers previously confirmed by esophagogastroduodenoscopy. The sensitivity of endoscopy for identifying scars was determined for these patients. In the second study, the extent of interobserver agreement was determined for 47 endoscopists who identified ulcer scars in endoscopic photographs of 30 sites of previous active gastric ulcers and 30 sites of previous active duodenal ulcers. The kappa coefficient of reliability was calculated to measure the interobserver agreement on the diagnosis of ulcer scars. RESULTS: Out of 190 patients eligible for analysis, 104 (54.7%) were found to have gastric or duodenal ulcer scars on endoscopy; there were no gastric or duodenal ulcer scars seen in the remaining patients (45%). In the second study, the kappa values for endoscopic diagnosis of gastric and duodenal ulcer scars were 0.14 (95% CI 0.13-0.16) and 0.29 (95% CI 0.27-0.32), respectively. The addition of indigo-carmine chromoendoscopy did not provide a statistically significant improvement in diagnostic concordance in patients with gastric ulcer scar since the kappa value for chromoendoscopic diagnosis was 0.15; 95% CI 0.13-0.17 as low as for un-contrasted scars. CONCLUSIONS: The sensitivity and concordance of endoscopic diagnosis of gastric and duodenal ulcer scars are not satisfactory for the use of endoscopy only to identify previous ulcer disease. To avoid the overlooking the previous clinical history of peptic ulcer diseases, the diagnosis of peptic ulcer scar has to be carefully done prior to NSAIDs administration.

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.

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.

A rare case of Barrett's adenocarcinoma including squamous cell carcinoma component.

We present a rare case of Barrett's cancer with a particular histology composed of various differentiated adenocarcinoma (AC) and squamous cell carcinoma (SCC) cells. A 52-year-old man with a long-standing complaint of heartburn visited a medical center for an annual check-up by esophagogastroduodenoscopy (EGD). Although high-grade reflux esophagitis with Barrett's esophagus was identified 3 years earlier, he had not visited a hospital for medication. In 2008, he underwent EGD and a 0-IIa + IIc type of superficial cancerous lesion was found in the long segment of Barrett's esophagus. The histology of this lesion was confirmed as adenosquamous carcinoma by biopsy specimens. Based on the results of computed tomography, endoscopic ultrasonography, and a barium study, the cancer was found to invade the submucosal layer, and the patient underwent surgery. A histological study after the surgery demonstrated various subtypes of AC, such as mucinous, signet-ring cell and tubular AC, with a focal SCC component. Barrett's AC containing SCC is very rare, and its carcinogenesis is of interest.