Endoscopic and histological risk stratification for gastric cancer using gastric intestinal metaplasia.

BACKGROUND AND AIM: Intestinal metaplasia (IM) of the gastric mucosa is strongly associated with the risk of gastric cancer (GC). This study was performed to investigate the usefulness of endoscopic and histological risk stratification for GC using IM. METHODS: This was a post-hoc analysis of a multicenter prospective study involving 10 Japanese facilities (UMINCTR000027023). The ridge/tubulovillous pattern, light blue crest (LBC), white opaque substance (WOS), endoscopic grading of gastric IM (EGGIM) score using non-magnifying image-enhanced endoscopy, and operative link on gastric IM assessment (OLGIM) were evaluated for their associations with GC risk in all patients. RESULTS: In total, 380 patients (115 with GC and 265 without GC) were analyzed. The presence of an LBC (limited to antrum: odds ratio [OR] 2.4 [95% confidence interval 1.1-5.0], extended to corpus: OR 3.6 [2.1-6.3]), the presence of WOS (limited to antrum: OR 3.0 [1.7-5.3], extended to corpus: OR 4.2 [2.1-8.2]), and histological IM (limited to antrum: OR 3.2 [1.4-7.4], extended to corpus: OR 8.5 [4.5-16.0]) were significantly associated with GC risk. Additionally, the EGGIM score (5-8 points: OR 8.8 [4.4-16.0]) and OLGIM (stage III/IV: OR 12.5 [6.1-25.8]) were useful for stratification of GC risk. The area under the receiver operating characteristic curve value for GC risk was 0.740 for OLGIM and 0.706 for EGGIM. CONCLUSIONS: The LBC, WOS, EGGIM, and OLGIM were strongly associated with GC risk in Japanese patients. This finding can be useful for GC risk assessment in daily clinical practice.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Clinical outcomes of endoscopic submucosal dissection for esophageal squamous cell carcinoma with esophageal varices: Multicenter retrospective study.

OBJECTIVES: Clinical outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) are obscure. We aimed to elucidate the clinical outcomes of ESD for ESCC with EVs in a multicenter, retrospective study. METHODS: We established a retrospective cohort of 30 patients with ESCC complicating EVs, who underwent ESD at 11 Japanese institutions. Rates of en bloc resection and R0 resection, procedure time, and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence, and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD. RESULTS: Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 min. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC. CONCLUSION: This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

Is blue light imaging without magnification satisfactory as screening for esophageal squamous cell carcinoma? Post-hoc analysis of multicenter randomized controlled trial.

OBJECTIVES: Narrow light observation is currently recommended as an alternative to Lugol chromoendoscopy (LCE) to detect esophageal squamous cell carcinoma (ESCC). Studies revealed little difference in sensitivity between the two modalities in expert settings; however, these included small numbers of cases. We aimed to determine whether blue light imaging (BLI) without magnification is satisfactory for preventing misses of ESCC. METHODS: This was a post-hoc analysis of a multicenter randomized controlled trial targeting patients at high risk of ESCC in expert settings. In this study, BLI without magnification followed by LCE was performed. The evaluation parameters included: (i) the diagnostic abilities of ESCC; (ii) the endoscopic characteristics of lesions with diagnostic differences between the two modalities; and (iii) the color difference between cancerous and noncancerous areas in BLI and LCE. RESULTS: This study identified ESCC in 49 of 699 cases. Of these cases, nine (18.4%) were missed by BLI but detected by LCE. In per-patient analysis, the sensitivity of BLI was lower than that of LCE following BLI (83.7% vs. 100.0%; P = 0.013), whereas the specificity and accuracy of BLI were higher (88.2% vs. 81.2%; P < 0.001 and 87.8% vs. 82.5%; P < 0.001, respectively). No significant endoscopic characteristics were identified, but the color difference was lower in BLI than in LCE (21.4 vs. 25.1; P = 0.003). CONCLUSION: LCE following BLI outperformed BLI in terms of sensitivity in patients with high-risk ESCC. Therefore, LCE, in addition to BLI, would still be required in screening esophagogastroduodenoscopy even by expert endoscopists.

Blue light imaging and linked color imaging as a screening mode for esophageal squamous cell carcinoma in high-risk patients: Multicenter randomized trial.

OBJECTIVES: Blue light imaging (BLI) and linked color imaging (LCI) are superior to conventional white light imaging for detecting esophageal squamous cell carcinoma (ESCC). Hence, we compared their diagnostic performances in ESCC screening. METHODS: This open-labeled, randomized controlled trial was performed at seven hospitals. Patients with a high risk of ESCC were randomly assigned to the BLI group (BLI followed by LCI) and LCI group (LCI followed by BLI). The primary end-point was the detection rate of ESCC in the primary mode. The main secondary end-point was its miss rate in the primary mode. RESULTS: In total, 699 patients were enrolled. The detection rate of ESCC did not significantly differ between the BLI and LCI groups (4.0% [14/351] vs. 4.9% [17/348]; P = 0.565); however, the number of patients with ESCC tended to be smaller in the BLI group (19 vs. 30). Notably, the miss rate of ESCC was lower in the BLI group (26.3% [5/19] vs. 63.3% [19/30]; P = 0.012) and LCI detected no ESCCs missed by BLI. The sensitivity was higher in BLI (75.0% vs. 47.6%; P = 0.042); on the other hand, the positive predictive value in BLI tended to be lower (28.8% vs. 45.5%; P = 0.092). CONCLUSIONS: The detection rates of ESCC did not significantly differ between BLI and LCI. Although BLI may have the potential to be advantageous over LCI for the diagnosis of ESCC, it is still unclear whether BLI is superior to LCI, and a further large-scale study is needed. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT1022190018-1).

Low serum pancreatic amylase levels as a novel latent risk factor for colorectal adenoma in non-alcohol drinkers.

BACKGROUND AND AIM: Obesity, insulin resistance, and metabolic alterations increase the risk of colorectal cancer and adenoma (CRA). Non-alcoholic fatty liver disease (NAFLD) or pancreatic disease (NAFPD) shares many risk factors with CRA that may have significant roles in its development; however, the relationship between CRA and NAFLD/NAFPD remains unclear. METHODS: This cross-sectional study recruited 712 eligible participants without current drinking who had undergone total colonoscopy as part of a health checkup. These participants were classified into a CRA group (n = 236) and a control group (n = 439), which consisted of individuals without CRA and a history of polyp resection. NAFLD and NAFPD were diagnosed based on abdominal ultrasonography findings. RESULTS: Non-alcoholic fatty liver disease was observed more frequently in individuals with CRA than in the control group (55.9% vs 41.6%, P < 0.01). There was no significant association between NAFPD and CRA; however, serum pancreatic amylase (P-amylase) levels were significantly lower in individuals with CRA. Although NAFLD was one of the factors increasing the presence of CRA (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.07-2.10), low P-amylase levels were significantly associated with the presence of CRA (OR, 1.73; 95% CI, 1.04-2.88) independent of age, sex, current smoking, obesity, metabolic alterations including insulin resistance, and NAFLD. CONCLUSIONS: Low serum P-amylase levels were a possible independent risk factor for CRA in the present study. The latent pancreatic exocrine-endocrine-gut relationship was considered a novel pathway involved in obesity-related CRA development, in non-alcoholic individuals.

Effects of anti-thrombotic drugs on all-cause mortality after upper gastrointestinal bleeding in Japan: A multicenter study with 2205 cases.

OBJECTS: Although anti-thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti-thrombotic agents on in-hospital mortality following UGIB. METHODS: Information on clinical parameters, including usage of anti-thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high-volume centers in Japan between 2011 and 2018. The all-cause in-hospital mortality rate was evaluated according to the usage of anti-thrombotic agents. RESULTS: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty-five (29.3%) patients used anti-thrombotic agents. The all-cause in-hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end-stage malignancy, 96 deaths (bleeding-related, n = 22 ; non-bleeding-related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti-thrombotic users was significantly higher than that in non-users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti-thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non-users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%). CONCLUSIONS: Although the usage of anti-thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti-thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti-thrombotic agents.

Nature and treatment outcomes of bleeding post-bulbar duodenal ulcers.

BACKGROUND: Although post-bulbar duodenal ulcers (PBDUs) could become a source of upper gastrointestinal bleeding, the whole picture of the disease is unknown. We compared the characteristic features and treatment outcomes after endoscopic hemostasis between PBDUs and bulbar duodenal ulcers (BDUs). METHODS: Data on duodenal ulcers with evidence of endoscopically-active bleeding were extracted from the data that were retrospectively collected from 12 institutes in Japan between 2011 and 2018. Rebleeding and in-hospital mortality were compared between patients with PBDUs and those with BDUs by logistic regression analyses. RESULTS: Among 468 consecutive patients with bleeding duodenal ulcers, 96 (20.5%) had endoscopically-confirmed PBDUs. PBDUs were more frequently observed in patients with a poor general condition in comparison to BDUs. The rates of rebleeding and in-hospital mortality in patients with PBDUs were approximately three times higher than those in patients with BDUs (PBDU vs. BDU: 29.2% vs. 10.2% [P < 0.0001] and 14.6% vs. 5.1% [P = 0.0029], respectively). Although the high in-hospital mortality in PBDUs could be explained, to a lesser extent, by the likelihood of rebleeding, and, to a greater extent, by the patients' poor general condition, the presence of a PBDU itself was largely responsible for the high rebleeding rates in PBDUs. CONCLUSION: This is the first study focusing on the nature and treatment outcomes of bleeding PBDUs. PBDUs were associated with much higher rebleeding and mortality rates in comparison to BDUs, and the likelihood of rebleeding may be derived from their unique anatomic location.

Kyoto classification risk scoring system and endoscopic grading of gastric intestinal metaplasia for gastric cancer: Multicenter observation study in Japan.

OBJECTIVES: The usefulness of endoscopic and histological risk assessment for gastric cancer (GC) has not been fully investigated in Japanese clinical practice. METHODS: In this multicenter observation study, GC and non-GC patients were prospectively enrolled in 10 Japanese facilities. The Kyoto classification risk scoring system, the Kimura-Takemoto endoscopic atrophy classification, the endoscopic grading of gastric intestinal metaplasia (EGGIM), the operative link on gastritis assessment (OLGA) and the operative link on gastric intestinal metaplasia assessment (OLGIM) were applied to all patients. The strength of an association with GC risk was compared. In addition, important endoscopic findings in the Kyoto classification were identified. RESULTS: Overall, 115 GC and 265 non-GC patients were analyzed. Each risk stratification method had a significant association with GC risk in univariate analysis. In multivariate analysis, OLGIM stage III/IV (odds ratio [OR] 2.8 [95% CI 1.5-5.3]), high EGGIM score (OR 1.8 [1.0-3.1]) and opened-type Kimura-Takemoto (OR 2.5 [1.4-4.5]) had significant associations with GC risk. In the Kyoto classification, opened-type endoscopic atrophy, invisible regular arrangement of collecting venules (RAC), extensive (>30%) intestinal metaplasia in the corpus in image-enhanced endoscopy, and map-like redness in the corpus were independent high-risk endoscopic findings. The modified Kyoto classification risk scoring system using these four findings demonstrated a better area under the receiver operating characteristic curve value (0.750, P = 0.052) than that of the original Kyoto classification (0.706). CONCLUSIONS: The OLGIM stage III/IV, high EGGIM score and open-typed Kimura-Takemoto had strong association with GC risk in Japanese patients. The modified Kyoto classification risk scoring system may be useful for GC risk assessment, which warrants further validation. (UMIN000027023).

Long-term endoscopic surveillance for Barrett's esophagus in Japan: Multicenter prospective cohort study.

OBJECTS: Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient-years in Japan, the long-term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort. METHODS: A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010-2012 and received at least one follow-up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma (EAC) were calculated as the number of events divided by patient-years of follow-up and were expressed as %/year. RESULTS: Overall, the median endoscopic follow-up period was 59.9 (first and third quartiles, 48.5-60.8) months, constituting a total of 427 patient-years of observation. Since two EAC cases developed, the cancer incidence was 0.47% (0.01%-1.81%)/year. The cancer incidence was 0.39% (-0.16% to 2.44%) in 232 patient-years and 0.31% (-0.13% to 1.95%)/year in 318 patient-years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow-up, 12 of 92 patients (13.0%) died, but none died from EAC. CONCLUSION: This is the largest prospective follow-up study with endoscopy to investigate the incidence of EAC in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large-scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs 1.2%/year).

Association between High Levels of Circulating Chemerin and Colorectal Adenoma in Men.

BACKGROUND: Obesity and metabolic syndrome are considered the risk factors of colorectal adenoma (CRA) and colorectal cancer (CRC). Chemerin is a novel adipocytokine associated with the development of gastric cancer, esophageal cancer, hepatocellular carcinoma, and CRC. However, the relationship between chemerin levels and CRA remains unclear. OBJECTIVE: This study is aimed at investigating the -association between serum chemerin levels and the development of CRA. METHODS: We conducted a total colonoscopy-based cross-sectional case-control study of 80 male patients with CRA and 80 male age-matched control individuals without CRA, according to their endoscopic findings. Serum chemerin concentrations were measured using a sandwich enzyme-linked immunosorbent assay kit, and the OR of CRA was calculated via logistic regression analysis. RESULTS: The mean serum chemerin level of the CRA group was significantly higher than that of the control group (7.9 ± 0.41 vs. 5.16 ± 0.34 ng/mL, p < 0.001). Serum chemerin level was positively correlated to the development of CRA (r = 0.34). Multivariate logistic regression analysis revealed that a high chemerin level was independently associated with the development of CRA (OR 2.82, 95% CI 1.39-5.72). CONCLUSIONS: Our findings indicated that increased serum chemerin levels are positively associated with the presence of CRA in men. Chemerin may play an important role in the development of CRA.

Antimicrobial effects of viscous mouthrinses containing cetylpyridinium chloride and isopropyl methylphenol.

PURPOSE: To evaluate the in vitro antimicrobial effect of low- and high-viscosity experimental mouthrinses containing cetylpyridinium chloride (CPC) and 4-isopropyl-3-methylphenol (IPMP) on Streptococcus pneumoniae, Klebsiella pneumoniae, Porphyromonas gingivalis, Streptococcus mutans, and Candida albicans. METHODS: Low- and high-viscosity experimental mouthrinses containing 0.05% CPC and 0.1% IPMP were fabricated. Non-viscous mouthrinses containing either CPC- or IPMP were used as controls. The antimicrobial activity (sterilization or exposure time) of mouthrinses was evaluated based on the bactericidal criterion of <10¹ viable cells in 0.1 mL of culture medium. RESULTS: The sterilization time of the low-viscosity experimental mouthrinse was shorter than that of the high-viscosity mouthrinse. However, whereas a 10-minute exposure to the low-viscosity mouthrinse resulted in no viable cells of C. albicans, neither the CPC- or IPMP mouthrinses had an antimicrobial effect for the same exposure time. These findings show that the low-viscosity experimental mouthrinse containing anodal CPC and neutral IPMP exhibited superior antimicrobial effects against pneumonia- and oral infection-related bacteria compared with the control mouthrinses. CLINICAL SIGNIFICANCE: In Japan, the oral care with the low-viscosity experimental mouthrinse containing CPC and IPMP as alternatives to those based on chlorhexidine are available for preventing the development of pneumonia- and oral infection-related bacteria.

Impaired Secretion of Glucagon-Like Peptide 1 in Patients with Colorectal Adenoma after an Oral Glucose Load.

BACKGROUND/AIMS: Obesity and insulin resistance are associated with an increased risk of colorectal adenoma (CRA). Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis through its amplification of insulin secretion in response to oral nutrients; however, its role in human CRA remains unknown. We investigated oral glucose-mediated GLP-1 secretion in patients with adenoma. METHODS: We performed a case-control study of 15 nondiabetic patients with pathologically diagnosed CRA and 10 age-matched healthy controls without adenoma. Plasma concentrations of active GLP-1 were measured during a 75 g oral glucose tolerance test. RESULTS: Mean waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR) values, the total areas under the curve (AUC) of glucose and insulin were significantly higher in patients with CRA than in controls. The total AUC of GLP-1 (p = 0.01) was lower in patients with CRA than in controls. Moreover, the total AUC of GLP-1 showed a negative correlation with WC, total AUC of glucose, and HOMA-IR. Multiple linear regression analyses revealed that the total AUC of GLP-1 was independently correlated with the number and maximum size of CRAs. CONCLUSION: GLP-1 could actively participate in the development of CRA in humans, particularly in patients with metabolic syndrome.

Preferential location of idiopathic peptic ulcers.

OBJECTIVE: Helicobacter pylori infection-negative, nonsteroidal antiinflammatory drugs (NSAIDs)-negative peptic ulcers, which are termed idiopathic peptic ulcers (IPUs), have been increasing worldwide. In this study, we investigated the preferential locations of gastric ulcers according to their cause (e.g., H. pylori and NSAIDs), with special attention to IPUs. MATERIAL AND METHODS: A total of 361 patients consecutively diagnosed with a peptic ulcer over a period of one year were classified into four groups according to H. pylori-infection status and NSAIDs usage. The ulcer location was divided into the antrum, angularis, and body, and was compared among the four ulcer groups. RESULTS: The ulcers of 43 patients were classified as IPUs. Compared with simple H. pylori ulcers, IPUs more preferentially located in the antrum (14% vs. 52%, p < 0.01). The difference was more pronounced in the analysis of IPUs in which patients with a history of H. pylori eradication or those with severe atrophic gastritis were excluded, and 79% of these IPUs were located in the antrum. With duodenal ulcers taken together, the vast majority of (86%) these IPUs occurred in the duodenal bulb or the antrum. The proportion of antral ulcers in NSAISs users also differed depending on the presence of concomitant H. pylori infection (positive: 22% vs. negative: 62%, p < 0.01). CONCLUSION: There was a striking difference in the ulcer location within the stomach depending on the cause of the ulcer, and IPUs predominantly occurred in the antrum. This information on the preferential locations of ulceration should provide endoscopists with some hints concerning the etiology of ulcers.

A Chronological Increase in Gastric Acid Secretion from 1995 to 2014 in Young Japanese Healthy Volunteers under the Age of 40 Years Old.

Gastric acid secretion levels are an important determinant of the manifestation of acid-related upper GI diseases such as gastroesophageal reflux disease. We recently reported that gastric acid secretion levels did not change from the 1990s to 2010s in H. pylori-negative asymptomatic Japanese outpatients with a mean age of 63 years old. However, because young people have a quite different lifestyle, including dietary pattern, from elderly people in Japan, it is worth investigating any chronologic changes in gastric acid secretion in younger generations. The aim of this analysis is to investigate the potential changes in gastric acid secretion from 1995 to 2014 in young Japanese healthy volunteers. Eighty-eight young Japanese healthy volunteers under the age of 40 with a mean age of 26 were extracted from a database accumulated from 1995 to 2014 for the present analysis. Their gastrin-stimulated gastric acid level was determined with the endoscopic gastrin test. In 76 H. pylori-negative subjects, gastric acid secretion levels showed a significant positive correlation with the calendar year when the test was performed (r = 0.27, p < 0.01). A similar trend was observed in 12 H. pylori-positive subjects. A chronological 5-year time period showed a significant positive association with gastric acid secretion in univariate and multivariate analyses (p < 0.01 and p = 0.01, respectively). Gastric acid secretion levels have been increasing in young Japanese healthy volunteers during the last 20 years. We need to monitor future trends in the prevalence of acid-related diseases such as gastro-esophageal reflux disease in Japan.

Helicobacter pylori-negative and non-steroidal anti-inflammatory drugs-negative idiopathic peptic ulcers show refractoriness and high recurrence incidence: Multicenter follow-up study of peptic ulcers in Japan.

BACKGROUND AND AIM: Helicobacter pylori-negative and non-steroidal anti-inflammatory drugs (NSAIDs)-negative idiopathic peptic ulcers (IPU) have attracted attention in Japan and other developed countries. The aim of the present study was to clarify the healing rate of IPU and the risk of recurrence. METHODS: We conducted a retrospective follow-up study of patients with peptic ulcer disease (PUD) who were diagnosed in our previous multicenter-prospective study. Three hundred and eighty-two patients from four institutions in the Tohoku district were enrolled. Enrolled subjects were divided into four groups according to H. pylori infection and intake of NSAIDs. In these patients, we checked treatment course, healing rate during 3 months, and recurrence rate. RESULTS: Healing rates in the: (i) simple H. pylori group; (ii) H. pylori (+)/ NSAIDs (+) group, (iii) simple NSAIDs group; and (iv) IPU group, were 95.0%, 94.9%, 73.3%, and 77.4%, respectively. The healing rate of the IPU group was significantly lower than that of both the simple H. pylori group and the H. pylori (+)/ NSAIDs (+) group (P < 0.01). The recurrence rate of 13.9% in the IPU group was much higher than the 2.1% in the simple H. pylori group (P < 0.01). Additionally, the cumulative recurrence rates by the Kaplan-Meier method in the IPU group were significantly higher than those of the simple H. pylori group (P = 0.015). CONCLUSION: We demonstrated that the clinical course of peptic ulcers is considerably different depending on the cause. IPU could be refractory to treatment and prone to recur compared with simple H. pylori ulcers.

A multicenter prospective study on the prevalence of Helicobacter pylori-negative and nonsteroidal anti-inflammatory drugs-negative idiopathic peptic ulcers in Japan.

BACKGROUND AND AIM: The prevalence of Helicobacter pylori-negative and nonsteroidal anti-inflammatory drug-negative peptic ulcers, commonly known as idiopathic peptic ulcers (IPUs), has been reported to be very low (0.9-2.6%) in Japan based on data from the 1990s. However, recent trends have yet to be been reported. Herein, we present a multicenter prospective analysis between 2012 and 2013 investigating current trends in the prevalence and characteristics of IPUs in Japan. METHODS: Clinical data of all peptic ulcer subjects detected via endoscopy at four participating hospitals were prospectively collected between April 2012 and March 2013. Enrolled subjects were classified according to H. pylori infection status and intake of nonsteroidal anti-inflammatory drugs. Multiple logistic regression analyses were used to determine the risk factors for IPUs. RESULTS: Of 382 enrolled patients with peptic ulcers, 46 (12%) were judged to have IPUs. Compared with those with simple H. pylori-positive ulcers, patients with IPUs were significantly older (P < 0.02) and more often had underlying comorbidities such as hypertension (P < 0.02) and hyperlipidemia (P < 0.05). Multivariate regression analysis indicated that the presence of multiple underlying diseases was the only significant risk factor for IPUs, with an odds ratio of 3.8 (95% confidence interval, 1.3-11.1). CONCLUSIONS: This study revealed that the prevalence of IPUs in patients with peptic ulcers in Japan is 12%, much higher than previously reported. Presence of multiple underlying comorbid diseases, rather than aging itself, is an important risk factor for IPUs.

Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions.

The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.

Esophageal carcinoid tumor treated by endoscopic resection.

The present report describes a rare case of esophageal carcinoid tumor that was treated by endoscopic resection. A 43-year-old woman underwent esophagogastroduodenoscopy at her family clinic for screening of the upper digestive tract and a small lesion resembling a submucosal tumor was detected in the lower esophagus. A biopsy sample from the lesion was diagnosed as esophageal carcinoid tumor and the patient visited our hospital for detailed examination. The tumor was approximately 3 mm in diameter and its surface appeared to be covered with normal squamous epithelium. The tumor had a shiny reddish surface without ulceration or erosion. Magnifying endoscopy with narrow-band imaging showed structures resembling reticular vessels under the epithelium. Endoscopic ultrasonography depicted the tumor as a low-echoic mass within the lamina propria. Computed tomography did not detect the tumor and no metastatic lesions were evident in other organs. With the patient's informed consent, the tumor was resected using endoscopic submucosal dissection, with a sufficient free margin in both the vertical and horizontal directions. Magnifying endoscopic examination showed the resected tumor to have abundant reticular vessels. Finally, the tumor was diagnosed immunopathologically as an esophageal carcinoid tumor (neuroendocrine cell tumor, grade 1), without lymphatic or vascular invasion.

[Characteristics of group A patients according to the ABC classification for gastric cancer risk screening].

In the ABC classification for gastric cancer risk screening, group A (Helicobacter pylori infection-negative, pepsinogen [PG]-negative) patients are assumed to be at low risk, but some patients do have atrophic gastritis and H. pylori infection. This study aimed to identify the characteristics of group A patients. Healthy adults in Yamagata City who underwent barium radiography and ABC classification participated in the survey. Patient radiographs were randomly interspersed and reviewed by two gastroenterologists who were blinded to the H. pylori and PG statuses. Group A patients (n=1462) was subclassified as follows: atrophic gastritis group, 21.5%; intermediate group, 15.7%; and no atrophic gastritis group, 62.8%. Elderly subjects and those with H. pylori antibody titers of 3.0-9.9U/ml should be carefully evaluated while interpreting the results of the ABC classification for gastric cancer risk screening.