Nocturnal Gastroesophageal Reflux Disease (GERD) and Sleep: An Important Relationship That Is Commonly Overlooked.

Gastroesophageal reflux disease (GERD) is a prevalent, chronic medical condition that affects 13% of the adult population globally at least once a week. Sleep disturbances are frequently encountered in up to 25% of the GERD patients, likely due to nocturnal gastroesophageal reflux (GER). With advance in diagnostic techniques allowing for an improved understanding of involved physiological mechanisms of nocturnal reflux, there is growing evidence of a bidirectional relationship between GERD and sleep disturbances. Furthermore, nocturnal GER is associated with more complicated GERD. Obstructive sleep apnea (OSA) and GERD also have been linked, but to what degree remains controversial. Treatment of nocturnal GER has been shown to improve both subjective and objective sleep measures. The therapeutic approach includes lifestyle modifications and medication individualization and optimization with proton-pump inhibitors serving as the mainstay of treatment. Antireflux surgery and newer endoscopic procedures have been demonstrated to control nocturnal GER.

Lubiprostone Induces Claudin-1 and Protects Intestinal Barrier Function.

INTRODUCTION: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. METHODS: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1ß) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. RESULTS: IFNγ, IL-6, IL-1ß, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1ß, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. CONCLUSION: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.

Barrett's esophagus patients are becoming younger: analysis of a large United States dataset.

BACKGROUND: Barrett's esophagus (BE), a complication of long-term gastroesophageal reflux disease (GERD), has been reported to affect 6-8% of those with heartburn. Most patients are males, Caucasians and middle aged. However, there are no recent demographic studies that evaluated the proportion trends of BE. We aimed to assess proportion trends of BE over an 11-year period, using a very large national dataset. METHODS: This was a population-based analysis of the national Explorys dataset. Explorys is an aggregate of electronic medical record database representing over 54 million patients. Proportions of BE's variables such as age, gender, race, BMI, and treatment with PPI were recorded during an 11-year period. BE patients were classified into seven age groups (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, ≥ 70 years old). Secular trends of the proportion of BE were assessed over time for each age group. RESULTS: The majority of patients diagnosed with BE were ≥ 70 years old across all calendar years. However, the proportion of BE patients who were ≥ 70 years old has significantly decreased between 2006 and 2016 (- 19.9%, p < 0.001). The proportion of patients with BE increased in all age groups but most prominently in the age groups, 30-39: 2.07%, 40-49: 3.64%, 50-59: 6.89%, 60-69: 6.18%, p < 0.001. BE was significantly more common in those who were Caucasian and male. PPI usage fell significantly in those who were ≥ 70 years old (- 20.8%, p < 0.001), but increased in the other remaining age groups. CONCLUSIONS: The proportion of BE patients who are 70 years and older has significantly dropped. Younger patients' groups have demonstrated the highest increase in the proportion of BE patients, especially those in the age group of 30-39 years old.

Most Patients With Gastroesophageal Reflux Disease Who Failed Proton Pump Inhibitor Therapy Also Have Functional Esophageal Disorders.

BACKGROUND & AIMS: As many as 45% of patients with gastroesophageal reflux disease (GERD) still have symptoms after receiving once-daily proton pump inhibitor (PPI) therapy. We aimed to compare reflux characteristics and patterns between responders and non-responders to once-daily PPI therapy using combined impedance-pH monitoring. METHODS: Patients who reported heartburn and/or regurgitation at least twice per week for 3 months while receiving standard-dose PPI therapy were assigned to the PPI failure group (n = 16). Patients who reported a complete resolution of symptoms on once-daily PPIs for at least 4 weeks were assigned to the PPI success group (n = 13). We collected demographic data and subjects completed the short-form 36 and the GERD health-related quality of life questionnaires. Patients then underwent upper endoscopy and combined esophageal impedance-pH monitoring while on PPI therapy. RESULTS: Four patients in the PPI success group (31%) and 4 patients in the PPI failure group (25%) had abnormal results from the pH test (P = 1.00). Most of the patients in the PPI failure group (75%) were found to have either functional heartburn or reflux hypersensitivity with GERD. Impedance and pH parameters did not differ significantly between the PPI failure and success group. CONCLUSIONS: We found no difference in reflux characteristics between patients with GERD who had successful vs failed once-daily PPI therapy. Most patients in the PPI failure group (75%) had functional esophageal disorders.

Chenodeoxycholic Acid Releases Proinflammatory Cytokines from Small Intestinal Epithelial Cells Through the Farnesoid X Receptor.

BACKGROUND/AIMS: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells. METHODS: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone. RESULTS: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release. CONCLUSIONS: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases.

Sex differences in associations among metabolic syndrome, obesity, related biomarkers, and colorectal adenomatous polyp risk in a Japanese population.

To investigate sex differences in the associations among metabolic syndrome, obesity, adipose tissue-related biomarkers, and colorectal adenomatous polyps, a cross-sectional, multicenter study was conducted on 489 consecutive individuals who underwent their first colonoscopy at 3 hospitals. Plasma concentrations of adiponectin and leptin, as well as homeostatic model assessment of insulin resistance were also evaluated. The presence and number of adenomatous polyps, including advanced adenoma, were higher in men than in women. Metabolic syndrome was a risk factor for adenomatous polyps in both sexes. Large waist circumference was an independent risk factor for adenomatous polyps in men, and high BMI and large waist circumference were risk factors for adenomatous polyps in women. Interestingly, low BMI was associated with large adenomatous polyps (≥10 mm) and advanced adenoma, and waist-hip ratio was involved in proximal adenomatous polyp development only in women. In contrast, the highest quartile of leptin concentration had a 3.67-fold increased adenomatous polyp risk compared with the lowest quartile only in men. These results indicate that regarding colorectal pathogenesis, sex differences were identified in obesity but not in metabolic syndrome. Visceral obesity and a high serum leptin level may be risk factors for colorectal adenomatous polyp development in Japanese men.

Noncardiac chest pain: diagnosis and management.

PURPOSE OF REVIEW: Noncardiac chest pain (NCCP) has been defined as recurrent chest pain that is indistinguishable from ischemic heart pain after excluding a cardiac cause. NCCP is a common and highly challenging clinical problem in Gastrointestinal practice that requires targeted diagnostic assessment to identify the underlying cause of the symptoms. Treatment is tailored according to the cause of NCCP: gastroesophageal reflux disease (GERD), esophageal dysmotility or functional chest pain. The purpose of this review is to discuss the current diagnosis and treatment of NCCP. RECENT FINDINGS: Utilization of new diagnostic techniques such as pH-impedance and high-resolution esophageal manometry, and the introduction of a new definition for functional chest pain have helped to better diagnose the underlying mechanisms of NCCP. A better therapeutic approach toward GERD-related NCCP, the introduction of new interventions for symptoms due to esophageal spastic motor disorders and the expansion of the neuromodulator armamentarium for functional chest pain have changed the treatment landscape of NCCP. SUMMARY: GERD is the most common esophageal cause of NCCP, followed by functional chest pain and esophageal dysmotility. The proton pump inhibitor test, upper endoscopy, wireless pH capsule and pH-impedance are used to identify GERD-induced NCCP. High-resolution esophageal manometry is the main tool to identify esophageal motor disorder in non-GERD-related NCCP. Negative diagnostic assessment suggests functional chest pain. Potent antireflux treatment is offered to patients with GERD-related NCCP; medical, endoscopic or surgical interventions are considered in esophageal dysmotility; and neuromodulators are prescribed for functional chest pain. Assessment and treatment of psychological comorbidity should be considered in all NCCP patients.

Effect of Vonoprazan, a Potassium-Competitive Acid Blocker, on the 13C-Urea Breath Test in Helicobacter pylori-Positive Patients.

BACKGROUND AND AIM: Vonoprazan (VPZ) is a new oral potassium-competitive acid blocker that has recently become available. The aim of this study was to investigate the effects of VPZ on the urease activity of H. pylori as measured by the 13C-urea breath test (13C-UBT). PATIENTS AND METHODS: A total of 60 patients (26 men, 34 women; mean age 53.2 ± 13.6 years) who were diagnosed as H. pylori-positive were recruited. The patients were randomly allocated to three treatment groups: lansoprazole (LPZ) 30 mg (n = 20), VPZ 20 mg (n = 20) once daily for 3 weeks, or the control group (n = 20). The 13C-UBT was carried out at baseline and after 3 weeks of treatment, and the baseline and after treatment results then compared. Δ13C‰ ≥ 2.5‰ was considered H. pylori-positive. RESULTS: Four patients failed to complete the medication and were omitted from the analysis; data from the LPZ group (n = 18), VPZ group (n = 18), and control group (n = 20) were analyzed. The control group showed no significant change in 13C-UBT data between baseline and the completion of 3-week treatment (baseline: 26.6 ± 23.0‰, completion: 21.1 ± 13.1‰). The 13C-UBT data at week 3 were significantly decreased in both the VPZ group (baseline: 32.8 ± 22.7‰, completion: 7.6 ± 9.2‰, p = 0.0002) and the LPZ group (baseline: 41.8 ± 33.4‰; completion: 9.6 ± 8.8‰, p = 0.0006) compared to baseline. CONCLUSIONS: VPZ treatment reduced the value of UBT, warning that UBT for patients with VPZ treatment should be evaluated carefully.

Claudin-2 expression is upregulated in the ileum of diarrhea predominant irritable bowel syndrome patients.

Intestinal epithelial barrier function is impaired in irritable bowel syndrome patients. Claudins are highly expressed in cells with tight junctions and are involved in the intestinal epithelial barrier function. The expression pattern of tight junction proteins in diarrhea-predominant irritable bowel syndrome have not been fully elucidated. We therefore recruited 17 diarrhea-predominant irritable bowel syndrome patients and 20 healthy controls. The expression of the tight junction-related proteins was examined in the ileal, cecal, and rectal mucosa of diarrhea-predominant irritable bowel syndrome patients using real-time PCR and immunofluorescence. Claudin-2 expression was high in the ileum of diarrhea-predominant irritable bowel syndrome patients. Claudin-2 expression was the same in cecum and rectal mucosa of control and diarrhea-predominant irritable bowel syndrome patients. Similarly, the expression of clauidn-1, claudin-7, JAM-A, occludin, and ZO-1 in the ileal, cecal, and rectal mucosa did not change between control and diarrhea-predominant irritable bowel syndrome samples. Infiltration of eosinophil and mast cells in the mucosa of ileum, cecum and rectum was evaluated using immunohistochemical staining and was not affected by diarrhea-predominant irritable bowel syndrome. Claudin-2 was expressed on the apical side of villi and crypts of ileal mucosal epithelial cells. Clauidn-2 expression is upregulated in diarrhea-predominant irritable bowel syndrome patients and may contribute to the pathogenesis of this condition.

Effects of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic treatment: analysis of molecular alterations by a randomised controlled trial.

BACKGROUND: Whether Helicobacter pylori eradication actually suppresses the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) remains controversial. The aims of this study were to clarify (1) the molecular markers related to carcinogenesis in intestinal metaplasia (IM) by a cross-sectional study, and (2) the changes of those markers by an open-label, randomised controlled trial (RCT) of H. pylori treatment. METHODS: First, we evaluated microsatellite instability (MSI), the methylation status at hMLH1, CDKN2A and APC genes, and immunoreactivity using the monoclonal antibody (mAb) Das-1 in IM in the background mucosa of 131 patients who underwent ER for gastric neoplasia and 22 chronic gastritis cases (control). Next, we performed an RCT to evaluate the changes of MSI between the H. pylori-eradicated (n=19) and non-eradicated patients (n=17) at 1 year among the H. pylori-positive patients. RESULTS: Microsatellite instability and mAb Das-1 reactivity showed significantly higher incidences in both the H. pylori-positive and -negative patients compared with the control group, thus suggesting that MSI and mAb Das-1 reactivity are associated with gastric neoplasia (OR=5.06 for MSI; OR=2.51 for mAb Das-1 reactivity). The RCT showed that H. pylori eradication did not provide significant reversals of any molecular alterations including MSI (the primary end point) and other methylation statuses and mAb Das-1 reactivity (secondary end points). CONCLUSIONS: H. pylori eradication did not produce significant changes in the molecular alterations related to carcinogenesis, suggesting that H. pylori treatment may not prevent the development of MGC in background mucosa with IM.

Morphological Characteristics of Early Gastric Neoplasms Detected After Helicobacter pylori Eradication.

BACKGROUND: Previous morphological studies indicated that the eradication of Helicobacter pylori (H. pylori) made gastric neoplasms endoscopically indistinct through the flattening and covering of tumors with a non-neoplastic epithelium (NE). AIM: To validate these alterations. METHODS: We reviewed and compared the endoscopic and histological findings of early gastric carcinomas and high-grade dysplasias resected endoscopically from H. pylori-infected and H. pylori-eradicated patients. The extent of NE covering a tumor was expressed as the histological length ratio of NE to the tumor. Tumor morphology was compared before and after therapies in patients who received H. pylori eradication treatments during the period from tumor discovery to endoscopic resection. RESULTS: NE-covered ratios were higher in the 59 tumors detected after the eradication of H. pylori than in the 152 tumors detected during the infection (median 8 vs. 0 %, respectively), whereas the frequency at which an elevated morphology and whitish discoloration of a tumor were observed was less (14 vs. 56 %, and 14 vs. 43 %, respectively). These were also independent characteristics for tumors detected after the eradication of H. pylori. Two elevated tumors showing whitish discoloration out of 16 tumors became endoscopically indistinct following H. pylori eradication treatments through the flattening of tumors and muting of the discoloration. CONCLUSION: The eradication of H. pylori promoted covering with NE, the flattening of tumors, and muting of the whitish discoloration, which may make a subset of tumors, potentially including whitish elevated neoplasms, indistinct.

Do endoscopic features suggesting eosinophilic esophagitis represent histological eosinophilia?

BACKGROUND: Esophageal linear furrows, corrugated rings, and/or white exudates are often seen in patients with eosinophilic esophagitis (EoE); however, whether these are specific to EoE remains unclear. Endoscopic surveillance of these features was conducted to determine whether these represent esophageal eosinophilia, which is essential for the diagnosis of EoE. PATIENTS AND METHODS: Two thousand seven hundred and sixty-three patients were enrolled consecutively. Target biopsy was carried out when the above features were seen. Histological eosinophilia was defined as 24 or more eosinophils per high-power field (HPF). Associations between features and eosinophilia were analyzed statistically. RESULTS: Two thousand five hundred and forty-five patients completed the study. Linear furrows, corrugated rings and white exudates were seen in 24, 15 and 45 patients, respectively. These findings somewhat overlapped. Among 58 biopsied patients withany of the above features, these features represented eosinophilia in 14% (3/21), 23% (3/13), and 5% (2/43), respectively. None of the 199 patients who received biopsy for other features had eosinophilia. Two of five eosinophilia patients were diagnosed with EoE. Multiple comparisons revealed that eosinophil counts in linear furrows and corrugated rings but not white exudates were significantly greater than those in other features (12, 9, 1, and <1 eosinophils/HPF on average, respectively). CONCLUSIONS: An endoscopic feature suggesting EoE does not always represent esophageal eosinophilia and is non-specific for EoE, although it reminds endoscopists of the presence of EoE. The diagnostic utility of linear furrows or corrugated rings for esophageal eosinophilia is superior to that of white exudates.

Association between obesity and Barrett's esophagus in a Japanese population: a hospital-based, cross-sectional study.

BACKGROUND: The association between obesity and Barrett's esophagus (BE) in the Japanese population remains unclear. The prevalence of BE and its associated risk factors was examined. METHODS: A cross-sectional study of 1581 consecutive individuals who underwent upper gastrointestinal endoscopy was conducted. The prevalence of endoscopically suspected BE (ESBE) was evaluated. Obesity was evaluated by body mass index (BMI, ≥ 25 kg/m2) and waist circumference (WC) (males, ≥ 85 cm; females, ≥ 90 cm). Because endoscopic diagnosis of ultra-short ESBE (<1 cm in extent) is difficult and highly unreliable, this type of ESBE was excluded from the study. RESULTS: In proton pump inhibitor (PPI) non-users, the prevalence of ESBE ≥ 1 cm was 5.6%. In univariate analysis, male sex and reflux esophagitis (RE) were significantly associated with BE, but BMI, WC, and reflux symptoms were not. In multivariate logistic regression analysis, only RE (odds ratio [OR] = 3.48, 95% confidence interval [CI] 1.89-6.41, p < 0.0001) was an independent risk factor for BE; obesity and the other factors were not. In contrast, RE (OR 5.67, p = 0.0004) and large WC (OR 5.09, p = 0.0005) were significant risk factors for ESBE ≥ 1 cm in PPI users. Only male sex, but not obesity or the other risk factors, was associated with an increased risk of RE in patients not taking PPIs. CONCLUSIONS: RE, but not obesity, may have an independent association with the risk of ESBE in the Japanese population. Furthermore, obesity measures were not independent risks for RE. Interestingly, PPI-refractory RE and large WC were risk factors for ESBE ≥1 cm in patients taking PPIs.

Use of scintigraphy to evaluate gastric accommodation and emptying: comparison with barostat.

BACKGROUND AND AIM: Scintigraphy is a useful noninvasive technique for assessment of gastric motility, especially emptying, but there is little knowledge of use of the technique to assess gastric accommodation. Therefore, to clarify the usefulness of scintigraphy as a technique for assessing gastric accommodation, we compared scintigraphy with barostat, the gold standard modality. METHODS: Twenty healthy volunteers (14 men, six women; mean age, 28.5 ± 5.4 years) were enrolled in the study. The volunteers ingested a radiolabeled ((99m) Tc) test meal and scintigraphic images were recorded. Radioactivity in the upper third and whole stomach was calculated to evaluate accommodation. In the barostat procedure, gastric accommodation was evaluated by measuring the maximum volume of the distended balloon. Thereafter, correlation between scintigraphic and barostat accommodation was investigated. Intra-and inter-observer variation of the scintigraphic test results were also assessed. Finally, the diagnostic performance of scintigraphy was evaluated by using sumatriptan as a positive control. RESULTS: Measurements of accommodation by scintigraphy and barostat correlated (r = 0.524, P < 0.05). Sumatriptan significantly increased scintigraphically measured gastric accommodation (with sumatriptan, 51.5 ± 16.4%; without sumatriptan, 38.4 ± 13.8%) (P < 0.01), and had significantly (P < 0.05) delayed 50% half emptying time at 60, 90, 120, and 150 min after the start of the experiment. The data from repeated scintigraphic tests were highly reproducible (r = 0.804) with significant differences not observed among the investigators (inter-observer variation = 0.932, intra-observer variation = 0.898). CONCLUSION: Gastric scintigraphy is a useful technique for assessing gastric accommodation and emptying.

The incidence of "silent" free air and aspiration pneumonia detected by CT after gastric endoscopic submucosal dissection.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is feasible as a treatment for early gastric cancer, it requires great skill to perform and may place patients at increased risk of a number of complications, including perforation and aspiration pneumonia. OBJECTIVE: To investigate the incidence of "silent" free air without endoscopic perforation and aspiration pneumonia detected by CT after ESD and risk factors for the development of these 2 conditions. DESIGN: Prospective cohort study. SETTING: Single academic center. PATIENTS: This study involved 87 patients with a total of 91 malignancies. INTERVENTION: All patients underwent chest and abdominal CT and blood biochemistry analysis before and 1 day after ESD. MAIN OUTCOME MEASUREMENTS: The incidence of silent free air and aspiration pneumonia after ESD and the related risk factors. RESULTS: Silent free air was identified in 37.3% of patients without perforation. Tumor location (the upper portion of the stomach), the presence of a damaged muscular layer during ESD, and procedure time, but not specimen size, were significantly associated with silent free air (P = .006, P = .04, P = .02, and P = .53, respectively). According to the receiver-operating characteristic analysis, the resulting cutoff value of the procedure time for silent free air was 105 minutes (67.7% sensitivity, 65.4% specificity). Only procedure time (≥ 105 minutes) was an independent predictor of silent free air development (odds ratio 3.23; 95% confidence interval, 1.21-8.64; P = .02). On the other hand, aspiration pneumonia was seen in 6.6% of patients. Silent free air and aspiration pneumonia did not affect hospitalization. LIMITATIONS: Single center and small number of patients. CONCLUSIONS: Silent free air is frequently observed after ESD, and longer procedure time (≥ 105 minutes) was an independent risk factor for silent free air. However, silent free air and aspiration pneumonia detected by CT are not associated with clinically significant complications.

Prospective randomized controlled trial to compare the effects of omeprazole and famotidine in preventing delayed bleeding and promoting ulcer healing after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are generally used to prevent delayed bleeding after endoscopic submucosal dissection (ESD) and to heal the artificial ulcers. However, it remains controversial whether PPIs or histamine-2 receptor antagonists (H(2) RAs) are more effective in preventing delayed bleeding after ESD. We prospectively compared the effects of omeprazole and famotidine in preventing delayed bleeding and promoting artificial ulcer healing after ESD. METHODS: A total of 158 patients (155 early gastric cancers and three adenomas) were randomly assigned to the PPI group (omeprazole 20 mg/day) or H(2) RA group (famotidine 40 mg/day) in a prospective randomized controlled trial. The primary end point was the incidence of hematemesis, melena, and/or a decrease in hemoglobin level of 2 g/dL or more requiring endoscopic hemostatic treatment. ESD-induced ulcer healing and changes in ulcer size were also compared at 6 weeks after ESD as a secondary end point. RESULTS: Of the 158 patients, two were excluded from analysis because they had been treated with a PPI before the present study. Accordingly, data from 77 PPI and 79 H(2) RA subjects were included for analysis. Delayed bleeding after ESD occurred in 6.5% of subjects (PPI group) and in 6.3% (H(2) RA group); there was no significant difference between the two groups. Likewise, the two groups were not significantly different with respect to ulcer stage or ulcer size reduction rate. CONCLUSIONS: Proton pump inhibitors are not superior to H(2) RAs for the prevention of delayed bleeding or the healing of artificially induced ulcers after ESD.

Feasibility and safety of endoscopic submucosal dissection for lesions in proximity to a colonic diverticulum.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) for diverticulum-associated colorectal lesions is generally contraindicated because of the high risk of perforation. Several studies on patients with such lesions treated with ESD have been reported recently. However, the feasibility and safety of ESD for lesions in proximity to a colonic diverticulum (D-ESD) have not been fully clarified. The aim of this study was to evaluate the feasibility and safety of D-ESD. METHODS: D-ESD was defined as ESD for lesions within approximately 3 mm of a diverticulum. Twenty-six consecutive patients who underwent D-ESD were included. Two strategic approaches were used depending on whether submucosal dissection of the diverticulum-related part was required (strategy B) or not (strategy A). Treatment outcomes and adverse events associated with each strategy were analyzed. RESULTS: The en bloc resection rate was 96.2%. The rates of R0 and curative resection in strategies A and B were 80.8%, 73.1%, 84.6%, and 70.6%, respectively. Two cases of intraoperative perforation and one case of delayed perforation occurred. The delayed perforation case required emergency surgery, but the other cases were managed conservatively. CONCLUSION: D-ESD may be a feasible treatment option. However, it should be performed in a high-volume center by expert hands because it requires highly skilled endoscopic techniques.

Endoscopically treated Cronkhite-Canada syndrome associated with minute intramucosal gastric cancer: an analysis of molecular pathology.

There have been no reports of Cronkhite-Canada syndrome (CCS) associated gastric cancer resected with endoscopy because it is very difficult to identify small cancers that are candidates for endoscopic resection. We report a case of CCS with gastric cancer treated with endoscopic submucosal dissection, and we evaluate the molecular pathological analysis of malignant transformation in patients with CCS. A 74-year-old man had an advanced rectal cancer and gastrointestinal polyposis after presenting with hypoproteinemia, partial hair loss and atrophic nails as well as hyperpigmentation on the hands. He was diagnosed as having CCS. On upper endoscopy, a 7 mm discolored polyp with an irregular microvascular pattern revealed by magnified narrow-band imaging (NBI) was identified in gastric diffuse CCS polyposis. This lesion was treated with endoscopic submucosal dissection and diagnosed as a flat, elevated-type, mucosal well-differentiated tubular adenocarcinoma without lymphatic or venous infiltration, and with tumor-free margins. Microsatellite instability was detected in both the cancer and the surrounding CCS polyps. Mucin-histochemical analysis of the cancer area showed the complete intestinal type, and thus may have differentiated the CCS polyps from that of the common gastric hyperplastic polyps. This case illustrates that a clue to detecting small cancers may be to look for the discolored lesion among reddish CCS polyposis and thereafter to observe the irregular vascular pattern with NBI endoscopy. From the viewpoint of genetic alterations, patients with CCS polyps are considered to be at high risk for developing gastric cancer, and therefore careful follow-up examinations are necessary for the early detection of malignancies.