Low potency of fecal immunological surveillance testing soon after negative colonoscopy or resection of low-risk adenoma in average-risk patients.

BACKGROUND: Postcolonoscopy surveillance colonoscopy based on positive fecal occult blood testing (FOBT) is often performed, although its long-term efficacy has not been established. The aim of this study was to clarify the low potency of FOBT surveillance at short intervals after colonoscopy. METHODS: Colonoscopy was performed in 1308 average-risk patients, based on positive results of immunological FOBT [fecal immunological test (FIT)]. Patients were stratified according to the length of time since their last colonoscopy and their colonoscopy results [no adenoma or 1-2 small (<10 mm) adenomas]. Tumor detection rates were determined. RESULTS: The baseline patients characteristics did not differ between the groups. The advanced lesion detection rate (ALDR) among the patients who had never undergone a colonoscopy was 21.9% [95% confidence interval (CI), 19.1-25.0%]. Among the patients who had no adenoma detected in the previous colonoscopy within the past 5 years, the past 5-10 years and over 10 years, the ALDRs were 2.5% (95% CI, 1.0-5.5%), 4.1% (95% CI, 1.5-9.4%) and 9.3% (95% CI, 3.1-22.2%), respectively. Among the patients who had 1-2 small adenomas, the ALDRs were 7.4% (95% CI, 3.4-14.8%), 12.1% (95% CI, 4.2-27.9%) and 27.8% (95% CI, 12.2-51.2%), respectively. Invasive cancer was not observed in any patients within 5 years since the prior colonoscopy. CONCLUSION: In average-risk patients whose prior colonoscopy detected no adenomas or low-risk adenomas, postcolonoscopy surveillance by FIT has a low positive predictive value within a 5-year interval.

A multicenter retrospective study of the esophageal triamcinolone acetonide-filling method in patients with extensive esophageal endoscopic submucosal dissection.

OBJECTIVE: Endoscopic submucosal dissection (ESD) for extensive esophageal cancer is sometimes associated with post-ESD stenosis, despite preventative steroid therapy. In this retrospective multicenter analysis, we evaluated the factors associated with therapy resistance. MATERIALS AND METHODS: We enrolled 73 patients with 75 extensive esophageal cancers treated with ESD. Stenosis prevention was performed using two esophageal triamcinolone acetonide (TA)-fillings, and repeated if stenosis was found on follow-up. Therapy-resistance factors associated with incidence of severe stenosis requiring endoscopic balloon dilation (EBD) were evaluated, including age, gender, previous treatment history, tumor location, morphology, resection size, histologic type, invasion depth, and horizontal resection grade (HR-grade 1, ≥ 9/12 and <10/12 of the circumference; grade 2, ≥ 10/12 and <11/12; grade 3, ≥ 11/12 but not circumferential; and grade 4, entirely circumferential). RESULTS: Severe stenosis occurred in 17.3%(13/75) of cases, with a median of two EBDs (range, 1-6 times). Severe stenosis was significantly associated with HR-grade elevation and previous treatment history (p < .05); multivariate analysis showed both as independent therapy-resistance factors (p < .05). Patients without previous treatment history demonstrated severe stenosis at 12.9%(9/70): 0%(0/26) HR-grade 1, 18.8%(3/16) grade 2, 17.6%(3/17) grade 3, and 27.3%(3/11) grade 4, showing a risk of HR-grade 2 or more resection but an acceptable stenosis prevention even after entirely circumferential resection. Conversely, patients with previous treatment history demonstrated severe stenosis at a high frequency of 80%(4/5). CONCLUSIONS: Esophageal TA-filling is a promising stenosis-preventive steroid therapy, even in entirely circumferential ESD cases. However, HR-grade 2 or more elevation and previous treatment history were independently associated with therapy resistance.

A case of phlegmonous gastritis after acute pharyngitis.

We report a case of phlegmonous gastritis that followed an episode of acute pharyngitis. A 21-year-old man visited our emergency room because of intense epigastric pain. Fourteen days before the visit, he had symptoms of a sore throat and high fever. He was diagnosed with acute pharyngitis and treated with antibiotics. Although the symptoms of acute pharyngitis were relieved, epigastric pain began 5 days before the emergency visit. Computed tomography showed diffuse gastric wall thickening, and emergent esophagogastroduodenoscopy revealed diffusely spreading hyperemic mucosa with multiple erosions. He was admitted with a diagnosis of acute phlegmonous gastritis and was treated with antibiotics. The antibiotic treatment was effective and resulted in resolution of his clinical symptoms and normalized C-reactive protein concentrations. On hospital day 29, he was discharged. However, he was re-admitted because of recurrence of phlegmonous gastritis 5 days after discharge and 15 days after finishing the antibiotics. Cultures of gastric biopsies and juice were both positive for Streptococcus constellatus/milleri. Antibiotic treatment was effective, and he recovered without recurrence. A possible association between upper respiratory infections and subsequent phlegmonous gastritis has been reported, and this case supports causality. However, further studies are needed to evaluate causality and pathogenesis.

Initial Computed Tomography Findings of Long and Distended Colon Are Risk Factors for the Recurrence of Sigmoid Volvulus.

BACKGROUND: Sigmoid volvulus is a common condition in elderly patients with elongated colons. Although endoscopic de-torsion is effective as the primary treatment of sigmoid volvulus, elective surgery is recommended because of the high risk of recurrence and high mortality rate. AIM: The aim of this study was to determine the risk factors for the recurrence of sigmoid volvulus. METHODS: Clinical records of patients treated at Shimane Prefectural Central Hospital were reviewed retrospectively. Among 41 sigmoid volvulus patients who were successfully treated by endoscopic de-torsion and followed up, 30 were observed over 1 year. Among the 30 patients, eight (26.7%) did not experience recurrence, while 22 (73.3%) did. Initial computed tomography (CT) findings indicating the sigmoid colon extending to the diaphragm or ventral to the liver were defined as "extension findings." Extension findings and sigmoid diameter were evaluated in relation to sigmoid volvulus recurrence. RESULTS: Extension findings were significantly more frequent in the recurrent group (77.3%) than in the nonrecurrent group (25.0%) (P = 0.009). Distended sigmoid colon diameter was significantly larger in the recurrent group (11.7 ± 3.8 cm) than in the nonrecurrent group (7.1 ± 1.1 cm) (P = 0.044). Receiver operating characteristic curve analysis demonstrated that the performance threshold was greater than 8.9 cm. Kaplan-Meier analysis showed the significantly high sigmoid volvulus recurrence rate in the patients with extension findings and a distended sigmoid colon greater than 8.9 cm. CONCLUSIONS: CT findings of a long and distended sigmoid colon in initial sigmoid volvulus are risk factors for the recurrence of sigmoid volvulus.

Clinical features of chronic hepatitis B patients with low hepatitis B surface antigen levels and determinants of hepatitis B surface antigen seroclearance.

BACKGROUND AND AIM: A low hepatitis B surface antigen (HBsAg) level is reported to be predictive of future HBsAg seroclearance. A hospital-based cohort study was conducted to clarify the clinical features of patients with low HBsAg levels and to demonstrate the usefulness of low HBsAg levels for predicting HBsAg seroclearance. METHODS: A total of 1459 patients with chronic hepatitis B were included in the study. Of these, 587 had repeated measurements for HBsAg levels and two or more records of HBsAg-positive results. HBsAg levels were measured with a commercially available HBsAg assay. Based on a cut-off index (COI) of 2000, a high HBsAg level was defined as HBsAg ≥2000 COI, and a low HBsAg level was defined as HBsAg <2000 COI. RESULTS: The proportion of patients with low HBsAg levels at baseline tended to increase with age. Patients with low HBsAg levels at baseline had significantly older age, lower transaminase levels, and lower hepatitis B virus (HBV) DNA levels than those with high HBsAg levels. The annual HBsAg seroclearance rate was 1.30%/year. The cumulative incidences of HBsAg seroclearance differed significantly by HBsAg level at baseline (<2000 vs ≥2000 COI), age (≥50 vs <50 years), and HBV DNA level (<4.0 vs ≥4.0 log copies/mL). Cox proportional hazards regression analyses showed that low HBsAg level (<2000 COI) and low HBV DNA level (<4.0 log copies/mL) were significantly associated with HBsAg seroclearance. CONCLUSION: Aging was one of the factors affecting HBsAg level. HBsAg seroclearance was significantly associated with low HBsAg level and low HBV DNA level at baseline.

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.

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).

Mid-esophageal Diverticular Bleeding in a Patient with Kyphosis.

Mid-esophageal diverticulum is a rare disease, formed by the traction caused by inflamed bronchial lymph nodes or by pulsion induced by motility disorder. We herein report a case of mid-esophageal diverticular bleeding in a patient with kyphosis who was taking an anti-platelet drug. She was successfully treated with endoscopic hemostasis. An 80-year-old woman presented to our emergency department with hematemesis. She had kyphosis and was taking dipyridamole for her chest pain. Emergent upper endoscopy revealed bleeding from a mid-esophageal diverticulum; hemostasis was achieved via clipping. Mid-esophageal diverticula can cause upper gastrointestinal bleeding. An endoscopic examination and hemostasis are effective treatments.

Large-cell neuroendocrine carcinoma arising from a gastritis cystica polyposa.

Gastritis cystica polyposa is a polypoid lesion that arises from the gastric mucosa at the gastrojejunal anastomotic site and is characterized by cystic dilation of the gastric glands. A 78-year-old man who underwent distal gastrectomy for a gastric ulcer with Billroth II reconstruction approximately 40 years previously, exhibited a gastritis cystica polyposa at the anastomotic site. Ulceration was observed on an annual endoscopic examination. Endoscopic ultrasonography revealed a submucosal hypoechoic mass with multiple cystic lesions. Gastrectomy was performed and histological examination revealed a large-cell neuroendocrine carcinoma with cystic dilation of the gastric glands. Here, we report the first case of a large-cell neuroendocrine carcinoma arising from a gastritis cystica polyposa. Endoscopic ultrasonography was effective at diagnosing a submucosal hypoechoic mass with cystic dilation of the gastric glands.

[A case of long-term survival in stage IV squamous cell carcinoma of the anal canal with multidisciplinary treatment].

A 60-year-old female presented to our hospital with anal pain. Colonoscopy (CS) revealed a tumor in the anal canal, which was diagnosed as squamous cell carcinoma by biopsy. Computed tomography (CT) showed multiple liver metastases. From these findings, we diagnosed the anal tumor as stage IV squamous cell carcinoma of the anal canal. Although CS and CT indicated disappearance of the primary tumor and liver metastases following chemoradiotherapy, brain metastasis developed during the disease course and was treated with radiotherapy and surgical resection. Administration of S-1 as adjuvant chemotherapy was continued, and the patient has remained alive for approximately six years without recurrence. To the best of our knowledge, this case can be considered as having the longest-term survival in stage IV squamous cell carcinoma of the anal canal.

Avoidance of platelet transfusion with readministration of lusutrombopag before radiofrequency ablation in hepatocellular carcinoma:a case report.

Platelet transfusions are generally administered to patients with liver cirrhosis and associated thrombocytopenia before radiofrequency ablation (RFA). Here, we describe a 77-year-old woman who was diagnosed with hepatitis C, liver cirrhosis, and hepatocellular carcinoma (HCC) in 2006. She underwent RFA in October 2014 and October 2015, with platelet transfusions. She was admitted to our hospital in July 2016 to receive RFA for recurrence of HCC. To avoid platelet transfusion before RFA, she was administered lusutrombopag. The platelet count increased, and she did not need a platelet transfusion. In November 2016, computed tomography revealed that HCC had recurred. Lusutrombopag was readministered to avoid platelet transfusion before performing RFA. Subsequently, her platelet count increased, platelet transfusion was avoided, with no side effects. The results obtained in this case are valuable because there is little information on readministration of lusutrombopag.

Proton pump inhibitor is a risk factor for recurrence of common bile duct stones after endoscopic sphincterotomy - propensity score matching analysis.

Background and study aims Recurrence of common bile duct stones (CBDS) in patients treated with endoscopic sphincterotomy (ES) can lead to deterioration in their quality of life. Although the pathology and related factors are unclear, we speculated that proton pump inhibiter (PPI) administration increases the risk of CBDS recurrence by altering the bacterial mixture in the bile duct. Patients and methods The primary endpoint of this retrospective study was recurrence-free period. Several independent variables considered to have a relationship with CBDS recurrence including PPI use were analyzed using a COX proportional hazard model, with potential risk factors then evaluated by propensity score matching analysis. Results A total of 219 patients were analyzed, with CBDS recurrence found in 44. Analysis of variables using a COX proportional hazard model demonstrated that use of PPIs and ursodeoxycholic acid (UDCA), as well as the presence of periampullary diverticula (PD) each had a hazard ratio (HR) value greater than 1 (HR 2.2, P = 0.007; HR 2.0, P = 0.02; HR 1.9, P = 0.07; respectively). Furthermore, propensity score matching analysis revealed that the mean recurrence-free period in the oral PPI cohort was significantly shorter as compared with the non-PPI cohort (1613 vs. 2587 days, P = 0.014). In contrast, neither UDCA administration nor PD presence was found to be a significant factor in that analysis (1557 vs. 1654 days, P = 0.508; 1169 vs. 2011 days, P = 0.121; respectively). Conclusion Our results showed that oral PPI administration is a risk factor for CBDS recurrence in patients who undergo ES.

Mucosal breaks show same circumferential distribution in majority of patients with recurrent reflux esophagitis.

Background and study aims Esophageal mucosal breaks in patients with reflux esophagitis (RE) have a unique circumferential distribution. However, the specific location of mucosal breaks during recurrence of RE remains unclear. We investigated the circumferential distribution of mucosal breaks in patients with recurrent RE and compared their location to that noted at the initial diagnosis. Patients and methods We retrospectively enrolled patients with recurrent RE with Los Angeles (LA) grade A-C who were treated at our University Hospital between July 1996 and June 2014. The circumferential distribution of esophageal mucosal breaks was evaluated at the time of the initial diagnosis and again at the time of recurrence. Information regarding clinical parameters, including proton pump inhibitor administration, presence of hiatal hernia, and mucosal atrophy, was also reviewed. Results A total of 114 patients with recurrent RE were examined during the study period, with a mean duration to recurrence after initial diagnosis of 39.4 months. The majority (72.8 %) had the same LA grade at recurrence. In addition, recurrent mucosal breaks in 96 (84.2 %) patients were observed to have occurred in the same circumferential location as at the initial diagnosis, while those in 18 (15.8 %) were observed in a different location. When recurrent lesions had a different location, the LA grade also tended to be different (P = 0.02). Conclusions We found that most patients with recurrent RE developed lesions in the same circumferential location as noted for the initial lesions. Those in different locations at recurrence were associated with a change in LA grade.

Similarities and differences among eosinophilic esophagitis, proton-pump inhibitor-responsive esophageal eosinophilia, and reflux esophagitis: comparisons of clinical, endoscopic, and histopathological findings in Japanese patients.

BACKGROUND: Esophageal eosinophilia is classified as either eosinophilic esophagitis (EoE) or proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE), depending on the response to PPI treatment. The aim of this study was to compare the clinical, endoscopic, and histopathological findings of EoE and PPI-REE in Japanese patients. In addition, the characteristics of these cases were compared with those of reflux esophagitis (RE) cases. METHODS: Eleven patients diagnosed with EoE, 16 with PPI-REE, and 39 with RE, who were all consecutively examined from 2005 to 2015 at Shimane University Hospital, were enrolled. Clinical, endoscopic, and histopathological esophageal findings in these groups were retrospectively examined and compared. RESULTS: The differences in the clinical characteristics of EoE and PPI-REE were not remarkable, though patients with EoE and PPI-REE were younger, presented a higher prevalence of allergic comorbidities, and complained of symptoms of dysphagia more frequently than those with RE. The only noteworthy differences between EoE and PPI-REE were more frequent reports of asthma (36.4 vs. 2.6 %) and food allergy (27.3 vs. 0 %) by patients with EoE (P < 0.05, P < 0.05, respectively). Endoscopic findings in patients with EoE and PPI-REE were similar, with the presence of esophageal erosions in a small percentage of PPI-REE cases being the only difference. There were no histopathological differences between EoE and PPI-REE. CONCLUSIONS: Comparisons of clinical, endoscopic, and histopathological findings between EoE and PPI-REE showed that these two types have similar characteristics, though EoE patients showed a higher atopic background. Predicting PPI responsiveness in cases with esophageal eosinophilia is difficult and requires further investigation.

Specific locations of linear furrows in patients with esophageal eosinophilia.

BACKGROUND AND AIM: Linear furrows are the most frequently found endoscopic abnormality in patients with esophageal eosinophilia (EE); however, the precise endoscopic features remain to be fully elucidated. Here, we aimed to clarify the endoscopic features of EE, essential for the diagnosis of eosinophilic esophagitis (EoE), by focusing on the specific locations of linear furrows in a Japanese population. METHODS: We enrolled 70 cases with EE (≥15 eosinophils/high-power field) who were diagnosed at our hospital and related facilities. Information regarding endoscopic findings and clinical parameters was retrospectively reviewed. Next, the position of linear furrows in relation to esophageal longitudinal folds (ridge or valley) was evaluated in each case and compared with the position of mucosal breaks in patients with reflux esophagitis. Finally, the relationship between linear furrows and eosinophilic infiltration was evaluated. RESULTS: Of the 70 EE patients, 63 (90%) had linear furrows. Those occurred in a radial pattern and were widespread throughout the lower to upper esophagus, and exclusively found in esophageal longitudinal mucosal fold valleys, not on ridges, which was different from the position of mucosal breaks in patients with reflux esophagitis. Increased eosinophilic infiltration was significantly more frequent in linear furrows in the valleys (93%) as compared to mucosa on adjacent ridges (60%) (P < 0.05). CONCLUSION: Investigation of these endoscopic characteristics, especially by focusing on linear furrows in esophageal mucosal fold valleys, may provide important clues for more accurate diagnosis of EoE.

Evaluation of esophageal intramural pseudo-diverticulosis using high-resolution manometry.

Esophageal intramural pseudo-diverticulosis (EIPD) is a rare disease characterized by multiple small flask-shaped pouches in the esophageal wall, with the predominant symptom of chronic progressive or intermittent dysphagia. However, its etiology and pathogenesis remain unknown. We present a case of EIPD evaluated with high-resolution manometry in a 75-year-old man with food impaction after eating beef, who came to our emergency department. The patient experienced similar episodes three times previously, though the cause was unknown. Computed tomography (CT) findings revealed diffuse wall thickness in the upper intrathoracic esophagus, while esophagogastroduodenoscopy showed multiple small depressions and several white plaque patches, and a barium meal esophagogram showed characteristic multiple small outpouching areas. From these findings, we diagnosed the patient with EIPD. In addition, high-resolution manometry revealed strong contractions in the distal esophagus. We started an administration of isosorbide dinitrate, because abnormal esophageal motility may have been causative of the condition and development of pseudo-diverticulosis. Thereafter, the patient had a good clinical course without food impaction. Elevated intra-esophageal luminal pressure caused by abnormal esophageal motility seems to be an important factor in the pathogenesis of EIPD in some cases.

Successful Endoscopic Management of Non-Healing Perforated Duodenal Ulcer with Polyglycolic Acid Sheet and Fibrin Glue.

In recent years, treatment techniques in which polyglycolic acid sheets are applied to various situations with fibrin glue have exhibited great clinical potential, and previous studies have reported safety and efficacy. We describe closure of a non-healing perforated duodenal ulcer with the use of a polyglycolic acid sheet and fibrin glue in an elderly patient who was not a candidate for surgery.

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.

Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers.

BACKGROUND/AIMS: Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. METHODS: Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. RESULTS: Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm(2)/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. CONCLUSIONS: Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults.