Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III): a multicenter prospective interventional study.

BACKGROUND: Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP. METHOD: A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period. RESULTS: 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %-5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %-94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %-92.4 %). CONCLUSION: IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed.

Cancer risk and genotype-phenotype correlation in Japanese patients with Cowden syndrome.

BACKGROUND: Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. METHODS: We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. RESULTS: Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. CONCLUSION: Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.

Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study IV): a multicentre, double-blind, randomised, two-by-two factorial design trial.

BACKGROUND: The only established treatment for preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) is colectomy, which greatly reduces patient quality of life. Thus, an alternative method is warranted. In this trial, we aimed to clarify the individual and joint effects of low-dose aspirin and mesalazine on the recurrence of colorectal polyps in Japanese patients with FAP. METHODS: This was a randomised, double-blind, placebo-controlled, multicentre trial with a two-by-two factorial design done in 11 centres in Japan. Eligible patients were aged 16-70 years and had a history of more than 100 adenomatous polyps in the large intestine, without a history of colectomy. Before the study, patients underwent endoscopic removal of all colorectal polyps of at least 5·0 mm in diameter. Randomisation was done with a minimisation method with a random component to balance the groups with respect to the adjustment factors of sex, age (<30 years vs ≥30 years), or smoking status at the time of entry. Patients and researchers were masked to the treatment group. There were four groups: aspirin (100 mg per day) plus mesalazine (2 g per day), aspirin (100 mg per day) plus mesalazine placebo, aspirin placebo plus mesalazine (2 g per day), or aspirin placebo plus mesalazine placebo. Treatment was continued until 1 week before 8 month colonoscopy. The primary endpoint was the incidence of colorectal polyps of at least 5·0 mm at 8 months and was assessed in the intention-to-treat population. Safety was assessed in the ITT population. We also did a per-protocol analysis including only patients who took at least 70% of the allocated study drug. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000018736, and is complete. FINDINGS: Between Sept 25, 2015, and March 13, 2017, 104 patients were randomly assigned to receive either aspirin or aspirin placebo (n=52) or mesalazine or mesalazine placebo (n=52). Two patients withdrew from the aspirin plus mesalazine placebo group. 26 (50%) of 52 patients who received no aspirin had colorectal polyps of at least 5·0 mm at 8 months, as did 15 (30%) of the 50 patients who received any aspirin, 21 (42%) of the 50 patients who received no mesalazine, and 20 (38%) of the 52 patients who received any mesalazine. The adjusted odds ratio for polyp recurrence was 0·37 (95% CI 0·16-0·86) in the patients who received any aspirin and 0·87 (95% CI 0·38-2·00) in any who received mesalazine. The most common adverse events were grade 1-2 upper gastrointestinal symptoms in three (12%) of 26 patients who received aspirin plus mesalazine, one (4%) of 24 patients who received aspirin plus mesalazine placebo, and one (4%) of 26 patients who received mesalazine plus aspirin placebo. There was one grade 4 event in the mesalazine plus aspirin placebo group, but not related to the treatment. INTERPRETATION: Low-dose aspirin safely suppressed the recurrence of colorectal polyps larger than 5·0 mm in patients with FAP. These results suggest an effect of low-dose aspirin for FAP and could be an alternative method for preventing colorectal cancer in FAP. FUNDING: Japan Agency for Medical Research and Development.

Clinical Characteristics and Risk Factors for Pneumocystis Jirovecii Pneumonia during Immunosuppressive Treatment in Patients with Ulcerative Colitis: A Retrospective Study.

AIMS: This study aimed to clarify the clinical characteristics of Pneumocystis jirovecii pneumonia (PJP) infection in patients with ulcerative colitis (UC) and to identify risk factors for PJP using a retrospective case-control study. METHODS: Of 4,525 patients with UC treated between 2007 and 2019, we identified those who satisfied the criteria for PJP. The Lichtiger clinical activity index (LCI) was compared between the initiation of immunosuppressive drug treatment and the onset of PJP. A retrospective case-control study was conducted using a PJP group and a non-PJP group. RESULTS: Nine patients experienced PJP, of whom two died. Since October 2014, there were no cases of PJP among UC patients aged ≥50 years who were prescribed three or more immunosuppressive agents given prophylactic sulfamethoxazole-trimethoprim (TPM-SMX). The median LCI (range) was 13 (8-17) at the initiation of treatment versus 2 (1-8) at PJP onset (p = 0.016). The median time to PJP onset was 83 days after treatment initiation. In the PJP group the median age was significantly greater (p = 0.022), three immunosuppressants were used significantly more frequently (p = 0.004), and the lymphocyte counts during treatment were significantly lower (p < 0.01) than in the non-PJP group. The cut-off lymphocyte count that distinguished PJP patients from non-PJP patients was 570/µL according to a receiver-operating curve analysis. CONCLUSIONS: Prophylactic administration of TPM-SMX prevented further cases of PJP. The onset of PJP occurred at the same time as the symptoms of UC were stabilizing and the immunosuppressive drugs were being reduced. Greater age, lower lymphocyte count, and treatment with three immunosuppressive drugs were risk factors for PJP.

Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial.

Background: Management of anticoagulants for patients undergoing polypectomy is still controversial. Cold snare polypectomy (CSP) is reported to cause less bleeding than hot snare polypectomy (HSP). Objective: To compare outcomes between continuous administration of anticoagulants (CA) with CSP (CA+CSP) and periprocedural heparin bridging (HB) with HSP (HB+HSP) for subcentimeter colorectal polyps. Design: Multicenter, parallel, noninferiority randomized controlled trial. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000019355). Setting: 30 Japanese institutions. Patients: Patients receiving anticoagulant therapy (warfarin or direct oral anticoagulants) who had at least 1 nonpedunculated subcentimeter colorectal polyp. Intervention: Patients were randomly assigned to undergo HB+HSP or CA+CSP and followed up 28 days after polypectomy. Measurements: The primary end point was incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis). The prespecified inferiority margin was -5% (CA+CSP vs. HB+HSP). Results: A total of 184 patients were enrolled: 90 in the HB+HSP group, 92 in the CA+CSP group, and 2 who declined to participate after enrollment. The incidence of polypectomy-related major bleeding in the HB+HSP and CA+CSP groups was 12.0% (95% CI, 5.0% to 19.1%) and 4.7% (CI, 0.2% to 9.2%), respectively. The intergroup difference for the primary end point was +7.3% (CI, -1.0% to 15.7%), with a 0.4% lower limit of 2-sided 90% CI, demonstrating the noninferiority of CA+CSP. The mean procedure time for each polyp and the hospitalization period were longer in the HB+HSP than in the CA+CSP group. Limitation: An open-label trial assessing 2 factors (anticoagulation approach and polypectomy procedure type) simultaneously. Conclusion: Patients having CA+CSP for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HB+HSP. Primary Funding Source: Japanese Gastroenterological Association.

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.

Esophagography in Patients With Esophageal Achalasia Diagnosed With High-resolution Esophageal Manometry.

BACKGROUND/AIMS: High-resolution esophageal manometry (HREM) is considered to be the gold standard for the diagnosis of achalasia. However, the Japan Esophageal Society recommends that esophagography is also accurate in either diagnosing or excluding the disorder. Accordingly, we compared the efficacy of esophagography and HREM in diagnosing achalasia patients with upper gastrointestinal symptoms. METHODS: HREM was performed in 126 patients with dysphagia. The final diagnosis of achalasia was done using HREM. Demographic data, symptoms, quality of life (QOL) were also obtained. We assessed the patients who were not able to be diagnosed by esophagography and compared the diagnostic values for esophagography with HREM-based achalasia diagnosis as the gold standard. RESULTS: A total of 48 cases of patients with achalasia, including 21 men and 27 women (mean age, 48.4 ± 19.6 years), were included in the study. Two patients were excluded. Of the remaining 46 patients, 36 (78.3%) patients were diagnosed as having achalasia by esophagography. The diagnostic sensitivity, specificity, and accuracy of esophagography were 78.3%, 88.0%, and 83.0%, respectively. Patients with type III achalasia had significantly lower physical QOL score than those with type I or II achalasia. Although the mental QOL score in patients with type III achalasia tended to decrease compared with that in patients with type I and II achalasia, the difference was not statistically significant. CONCLUSIONS: Diagnosing esophageal achalasia by using esophagography alone has limited yield. Therefore, HREM should be used in patients with dysphagia and in whom achalasia cannot be diagnosed using EGD or esophagography.

Rectal Foreign Body of Eggplant Treated Successfully by Endoscopic Transanal Removal.

Transanal rectal foreign body implies that a foreign body has been inserted transanally due to sexual orientation or other reasons and cannot be removed. Such cases require emergency measures because foreign bodies often present difficulties in manual removal or endoscopic removal and may even require surgery when peritonitis due to gastrointestinal perforation occurs. We report a patient in our hospital who had a rectal foreign body inserted into the deep part of the proctosigmoid that could be removed endoscopically. A 66-year-old man visited our hospital because of an eggplant which had been inserted into his rectum by his friend and could not be removed. Since plain abdominal computed tomography showed a foreign body thought to be an eggplant in the proctosigmoid, the foreign body was captured and removed with a snare under lower gastrointestinal endoscope guidance.

Are the Symptoms of an NSAID-Induced Ulcer Truly Milder Than Those of an Ordinary Ulcer?

OBJECTIVE: The percentage of patients with nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin- (LDA-) induced ulcers who complain of gastrointestinal symptoms has generally been considered to be low. The aim of this study was to examine and compare the symptoms and quality of life (QOL) at peptic ulcer onset. METHODS: This study involved 200 patients who were confirmed by endoscopy to be in the acute stage of gastroduodenal ulcer (A1-H1). Patients completed a self-administered questionnaire (Global Overall Symptom score and SF-8) at ulcer onset, and data were compared between NSAIDs/LDA ulcers and non-NSAIDs/LDA ulcers. RESULTS: The upper gastrointestinal symptoms score was significantly lower for patients using LDA only (20.5 ± 9.4 in the nonusing group, 19.6 ± 8.6 in the NSAIDs-only group, 16.7 ± 11.6 in the LDA-only group, and 18.5 ± 7.2 in the NSAIDs/LDA group, P < 0.05). The QOL score (physical summary) was significantly lower in the NSAID group (42.1 ± 9.9) than in the nonusing group (47.6 ± 7.6) (P < 0.05). Patients' characteristics showed no significant differences among the groups, with the exception of age. CONCLUSION: The severity of upper abdominal symptoms at peptic ulcer onset was similar between NSAID users and nonusers.

Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals.

BACKGROUND/AIMS: When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. METHODS: Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. RESULTS: When compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P 〈 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P 〈 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P 〈 0.01) and 60 minutes (20.3 ± 6.7 minutes, P 〈 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. CONCLUSION: Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.

Analysis of risk factors for colonic diverticular bleeding and recurrence.

The increase in incidence of colonic diverticular bleeding is relative to an age-related rise in the incidence of colonic diverticulosis and use of antithrombotic medication. However, risk factors related to the onset, recurrence, and prophylaxis have not been established. Therefore, we aimed to determine risk factors for the onset and recurrence of colonic diverticular bleeding.An age- and sex-matched case-control study was performed to assess the risk factors for the onset of colonic diverticular bleeding. The distribution of diverticulosis, comorbidity, and medication were evaluated from medical records. We also assigned patients with a first-time bleeding into groups with and without rebleeding during follow-up to determine risk factors for recurrence.Bilateral colonic diverticulosis, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), and anticoagulants were significant risk factors for the onset of colonic diverticular bleeding on multivariate analysis. In contrast, the use of selective cyclooxygenase-2 (COX-2) inhibitor was not a risk factor for the onset. The incidence of bleeding in direct oral anticoagulant and warfarin users was not different between the 2 groups. The cumulative recurrence rate at 1 year was 15%. Recurrence rate was significantly higher in patients with a prior history of colonic diverticular bleeding than those without. Steroid use was associated with recurrence.Extensive distribution of diverticulosis and use of nonselective NSAIDs, LDA, and anticoagulants are regarded as risk factors for the onset of colonic diverticular bleeding. In addition, a prior history of colonic diverticular bleeding is related to the recurrence.

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.

Prevalence of Gastric Motility Disorders in Patients with Functional Dyspepsia.

BACKGROUND/AIMS: Gastric motility abnormalities have been considered to be pathophysiological features of functional dyspepsia (FD) that are closely related to dyspepsia symptoms, especially postprandial distress syndrome (PDS). The aims of this study are to (1) investigate the prevalence of gastric motility disorders and (2) evaluate the association between gastric motility abnormalities and dyspeptic symptoms using gastric scintigraphy in the PDS type of FD. METHODS: Forty healthy subjects and 94 PDS type FD patients were enrolled in the study. The volunteers and patients ingested a radiolabeled (technetium-99m) solid test meal, and scintigraphic images were recorded. Gastric accommodation and emptying were assessed by scintigraphic imaging. The patients' dyspeptic symptoms were also explored using self-completed symptom questionnaires with 10 variables (4 scales, 0-3 points) at the same time. RESULTS: In 94 Japanese FD patients, the prevalence of impaired gastric accommodation and delayed emptying were 14.9% (14/94) and 10.6% (10/94), respectively. Gastric motility abnormalities were seen in 25.5% (24/94) of FD patients. There was no association between gastric motility abnormalities and dyspeptic symptoms. CONCLUSIONS: Gastric motility abnormalities were seen in 25.5% of Japanese PDS type FD patients. However, there was no association between gastric motility abnormalities and dyspeptic symptoms on gastric scintigraphy.

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.

A novel prostanoid EP1 receptor antagonist, ONO-8539, reduces acid-induced heartburn symptoms in healthy male volunteers: a randomized clinical trial.

BACKGROUND: Patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) have unmet clinical needs. Recently, we reported that esophageal prostaglandin E2 (PGE2) plays a crucial role in the generation of heartburn. In the present study, we focused on the PGE2 receptor, EP1, and investigated the effects of ONO-8539, a novel EP1 receptor antagonist, on heartburn symptoms in healthy male volunteers. METHODS: This prospective, double-blind, placebo-controlled, two-period crossover study was performed in 20 healthy male subjects. The novel prostanoid EP1 receptor antagonist, ONO-8539 (450 mg), was administered once 4 h prior to acid perfusion test. During the test, hydrochloric acid (0.15 mol l-1) was perfused into the lower esophagus for 30 min. Acid perception threshold was quantified by the time to first sensation of heartburn and intensity of GI symptoms determined using a validated categorical rating scale, and the area under the curve (AUC) as the total symptom score. RESULTS: ONO-8539 significantly reduced a total heartburn symptom score, not other upper GI symptom scores, during acid perfusion compared with placebo (AUC for heartburn, 85.0 ± 10.6 for placebo and 56.5 ± 7.2 for ONO-8539; P < 0.01), and significantly extended the time to first sensation of heartburn compared with placebo (5.7 ± 4.3 min for placebo and 9.7 ± 7.2 min for ONO-8539; P < 0.05). CONCLUSIONS: ONO-8539 attenuated acid-induced heartburn in healthy male subjects, suggesting that EP1 receptors play a role in generation of heartburn symptoms. ONO-8539 is a potential novel therapeutic option for controlling heartburn symptoms in GERD patients. Clinical Trials Registry No: UMIN000015753.

Genetic instability, CpG island methylator phenotype, and proliferative activity are distinct differences between diminutive and small tubular adenoma of the colorectum.

It is recommended that small (6-10 mm) lesions be treated with endoscopic resection (ER), whereas diminutive (≤5 mm) lesions are not currently an indication for ER according to the Japanese guidelines. The aim of this study was to evaluate the molecular alterations, and therefore treatment indications, in diminutive versus small tubular adenoma (TA). We prospectively analyzed genetic instability, including microsatellite instability and loss of heterozygosity, methylation status, KRAS/BRAF mutations, and Ki-67 staining in 96 TAs without a villous component. Although no microsatellite instability was identified in either diminutive or small TAs, genetic instability was seen in small TAs (9.1%) but not diminutive TAs (P = .04). In addition, the low-level CpG island methylator phenotype (CIMP-L) was more frequently observed in small TAs (31.8%) than in diminutive TAs (P = .01). Thus, genetic instability and CIMP-L were associated with small TAs, and only CIMP-L was an independent predictive marker for small TAs (odds ratio, 3.29; P = .03). Intriguingly, the Ki-67 proliferative index tended to be higher in small TAs than in diminutive TAs (P = .06) and higher in TAs with CIMP-L than in those without CIMP (P = .08). KRAS mutations were seen in codon 12 in 5.2% of TAs, but no BRAF gene mutations were found. As the molecular events and proliferative activity for the progression may increase from diminutive to small TAs, small TAs should be treated with ER, whereas a "predict, resect, and discard" strategy may be acceptable in most diminutive lesions except flat and depressed-type lesions, in keeping with the current strategy in the West.

A double-blind placebo controlled study of acotiamide hydrochloride for efficacy on gastrointestinal motility of patients with functional dyspepsia.

BACKGROUND: Acotiamide is widely used to improve symptoms in patients with functional dyspepsia (FD) in multiple large-scale clinical studies, but there are few reports about the drug's mechanism of action. The aim of this study was to assess the effects of acotiamide on gastric accommodation and gastric emptying, gastrointestinal symptoms, and health-related quality of life (HR-QOL) in a placebo-controlled study. METHODS: We conducted a randomized, double-blind placebo-controlled study. Fifty Japanese FD patients were randomly assigned to either placebo (n = 25) or acotiamide 100 mg × 3/day for 2 weeks (n = 25). At baseline and at 2 weeks of treatment, we evaluated the patients' gastric motility using scintigraphy to determine the accommodation and emptying values, gastrointestinal symptom rating scale (GSRS), HR-QOL (SF-8), and anxiety and depression scale (HADS). RESULTS: Four patients failed to complete the medication regimen and were omitted from analysis; data from 24 placebo patients and 22 acotiamide patients were analyzed. Acotiamide significantly increased gastric accommodation compared to the placebo (p = 0.04 vs. p = 0.08; respectively). Acotiamide significantly accelerated gastric emptying (50 % half-emptying time) (p = 0.02 vs. p = 0.59). Acotiamide significantly improved the total GSRS scores compared to placebo (p = 0.0007 vs. p = 0.14). HR-QOL did not differ significantly between the two groups, but acotiamide significantly improved the HADS anxiety score compared to placebo (p = 0.04 vs. p = 0.20). CONCLUSIONS: Our placebo-controlled study demonstrated that acotiamide significantly increased both gastric accommodation and gastric emptying in Japanese FD patients. Acotiamide also improved the patients' dyspeptic symptoms and anxiety score. Clinical Trials Registry no: UMIN000013544.

Esophageal stricture after endoscopic submucosal dissection treated successfully by temporary stent placement.

The growing use of endoscopic submucosal dissection (ESD) has enabled the highly curative treatment of early esophageal cancer. The circumferential extent of the tumor is reportedly related to the frequency of post-treatment stricture, with postoperative esophageal stricture reported to occur frequently when the post-resection mucosal defect exceeds 75 % of the esophageal luminal circumference. In some clinical cases, locally injected or orally administered steroids aimed at preventing post-treatment stricture fail to prevent re-stricture. Only two prior reports have investigated temporary stent placement for stricture after ESD for early esophageal cancer, and consensus is lacking on the appropriate duration and timing of stent placement. Here, we report our experience with a case of stricture after ESD for early esophageal cancer, in which temporary stent placement was effective for releasing the stricture for at least 6 months.