Megumi Hara

Clinical symptoms in endoscopic reflux esophagitis: evaluation in 8031 adult subjects.

This study aimed to evaluate the correlation between symptoms and endoscopic findings in reflux esophagitis. Subjects, 8031 persons without medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia, and acid regurgitation by associated medical staff before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) were classified as positive reflux esophagitis, and 2223 (27.7%) had heartburn, 1522 (19.0%) had dysphagia, 493 (6.1%) had odynophagia, and 1466 (18.3%) had acid regurgitation. Multivariate analysis indicated that the symptom most related to esophagitis was heartburn (odds ratio: 2.46), although ∼40% of subjects with grade C or D did not complain of heartburn. Regarding the other symptoms, less than 30% subjects with severe esophagitis complained of the symptoms and the odds ratio was ∼1. These results indicate that endoscopic esophagitis was not equivalent to any reflux symptoms from which subjects suffered in their daily lives.

Risk factors for complications of endoscopic submucosal dissection in gastric tumors : analysis of 478 lesions

PurposeEndoscopic submucosal dissection (ESD) technique has facilitated en bloc removal of widely spread lesions from the stomach. This retrospective study aimed to determine factors associated with serious complications of ESD.MethodsBetween December 2001 and March 2007, we have performed ESD for 478 lesions in 436 patients. We experienced 39 patients with post-operative bleeding and 17 patients with perforation. Risk factors of patients who received ESD in gastric mucosal tumors for complications were evaluated, focusing on resected size, location, scar lesions, operation time, and experience of endoscopists. We evaluated the patients’ background characteristics including sex, age, body mass index (kg/m2), drug history of anticoagulant, and underlying diseases including cerebrovascular disorder, ischemic heart disease, liver dysfunction, renal dysfunction, hyperuricemia, hypertension and diabetes mellitus.ResultsMultivariate analysis indicated a risk factor for perforation was long operation time. Multivariate analysis indicated a significant risk factor for post-operative bleeding was size of the resected tumor.ConclusionsThis study indicated risk factors for serious complications of ESD. Large resected tumor size was a risk factor for post-operative bleeding, while long operation time was a risk factor for perforation. Information regarding operation risk factors should be useful for planning strategies for ESD.

A polymorphism in the promoter of the CD14 gene (CD14/-159) is associated with the development of coronary artery lesions in patients with Kawasaki disease

OBJECTIVEnTo investigate whether a polymorphism in the CD14 gene is associated with Kawasaki disease (KD).nnnSTUDY DESIGNnWe extracted DNA from the whole blood of 69 control children and 67 patients with KD. We determined a polymorphism in the CD14 gene at position -159 upstream from the major transcription site (CD14/-159) by restriction fragment assay. We then investigated the association between CD14/-159 and the onset of KD and development of coronary artery lesion (CAL).nnnRESULTSnThe genomic and allelic frequencies of the polymorphism were not different between normal children and KD patients. The KD patients with TT genotypes at CD14/-159 had more CAL complications than those with CT and CC (OR, 4.05; 95% CI, 1.34-12.22). The frequencies of the T allele was significantly higher than that of the C allele in KD patients with CAL (OR, 2.20; 95% CI, 1.23-3.94). Their data were confirmed in the patients whether the patients were treated with intravenous gamma-globulin. KD patients with TT genotypes had significantly higher levels of C-reactive protein and vascular endothelial growth factor, which had previously been reported as risk factors for CAL, than those with CC genotypes.nnnCONCLUSIONnThese results indicate that the T allele and TT genotype at CD14/-159 are risk factors for CAL in KD, and that the development of CAL in KD may be related to the magnitude of CD14 toll-like receptor response.

NSAIDs are a significant risk factor for colonic diverticular hemorrhage in elder patients: Evaluation by a case-control study

Background and Aim:u2002 Diverticular bleeding is a common cause of lower gastrointestinal hemorrhage. Several factors, including use of non‐steroidal anti‐inflammatory drugs (NSAIDs), antithrombotic agents and arteriosclerosis, could be risk factors. The aim of this study is to identify these risk factors.

Low-dose aspirin is a prominent cause of bleeding ulcers in patients who underwent emergency endoscopy

ObjectiveThis study aimed to clarify the current situation of bleeding peptic ulcers and examined the temporal changes in the pathogenic mechanisms requiring emergency endoscopy.Patients and methodsStudy subjects were 285 bleeding peptic ulcer patients who received emergency endoscopy in Saga Medical School Hospital between 2000 and 2007. The ratios of H. pylori infection, NSAID use and low-dose aspirin use were analyzed for differences between the two periods by chi-square test. Logistic regression analysis was used to investigate factors such as patient characteristics that influenced the differences between each period.ResultsA total of 221 (77.5%) patients were identified as H. pylori-positive. One hundred (35.1%) patients reported a history of NSAID use within 4xa0weeks. Among NSAID users, 41 patients received daily low-dose aspirin. One hundred forty-one patients had bleeding ulcers in 2000–2003 and 144 patients in 2004–2007. The odds ratio (OR) between the periods was 0.806 (95% CI, 0.461–1.409) for H. pylori infection and 1.590 (95% CI, 0.973–2.598) for NSAID usage. In contrast, the proportion of patients who took low-dose aspirin was 9.9% in the first period and 18.8% in the second period, and the difference was statistically significant (OR 2.093; 95% CI, 1.047–4.185). Logistic regression analysis revealed that cardiovascular disease and cerebral vascular disease were associated with aspirin use.ConclusionThis study indicates that the causes of bleeding ulcers are changing, and the increasing use of low-dose aspirin might become a major cause of bleeding ulcers.

Hepatitis C virus infection enhances insulin resistance induced by visceral fat accumulation

Background/Aims: To clarify the impact of visceral obesity on hepatitis C virus (HCV)‐infected patients, we examined the relationship between insulin resistance development and visceral fat accumulation.

Smoking and risk of premature death among middle-aged Japanese: Ten-year follow-up of the Japan Public Health Center-based prospective study on cancer and cardiovascular diseases (JPHC study) cohort I

To update the evidence on the association between smoking and mortality, we analyzed data from a population‐based prospective study in Japan. In total, 19 950 men and 21 534 women aged 40–59 who reported their smoking history and had no serious disease at baseline survey were followed. During 1990–1999, 1014 men and 500 women died. Smokers were associated with an unhealthy life‐style. Relative risks (RRs) for selected cause of death due to smoking were slightly attenuated by adjusting for possible confounding factors. Age‐ and area‐adjusted RRs of male current smokers compared with never smokers were 1.66 (95% confidence intervals (CI): 1.40, 1.95) for all causes, 1.69 (1.31, 2.18) for all cancers, 1.67 (1.20, 2.34) for all circulatory system disease, and 1.63 (1.24, 2.15) for other causes, while those of females were 2.03 (1.52, 2.73), 2.06 (1.35, 3.15), 2.99 (1.75, 5.11), 1.31 (0.69, 2.51), respectively. After adjusting for multivariate variables, the corresponding RRs of male smokers were 1.55 (1.29, 1.86), 1.61 (1.20, 2.15), 1.41 (0.97, 2.03), and 1.61 (1.17, 2.19), against 1.89 (1.36, 2.62), 1.83 (1.14, 2.95), 2.72 (1.45, 5.07), and 1.39 (0.71, 2.73) for females. Twenty‐two percent of death from all causes, 25% of all cancer, and 17% of all circulatory system disease deaths, could be attributed to cigarette smoking in males, and 5%, 4%, and 11% in females, respectively. Cumulative dose as indicated by pack‐years was clearly associated with cancer death. These findings provided information as to the quantitative risk for premature death due to smoking among middle‐aged Japanese men and women, and showed that the elevated risk was not explained by the unhealthy lifestyle of smokers.

Dysphagia associated with gastroesophageal reflux disease is improved by proton pump inhibitor

This study aimed to determine whether dysphagia associated with gastroesophageal reflux disease was effectively treated with rabeprazole, a proton pump inhibitor. Sixty-eight outpatients with gastroesophageal reflux-associated dysphagia were enrolled in this study. Endoscopic esophagitis was confirmed in 52 of 68 subjects. The proton pump inhibitor rabeprazole was administered at 20 mg daily for 8 weeks. Rabeprazole was administered for a further 6 months to 16 subjects whose dysphagia was improved (10 mg/day) and 5 of these underwent 24-hr esophageal pH monitoring before and after treatment. Dysphagia was completely resolved in 40 of 68 subjects, which were categorized in Group I. Dysphagia improved partially in 20 subjects and was unchanged in 8 subjects. These 28 subjects were categorized into Group II. Comparison was made between Group I and Group II and multivariate analysis demonstrated that the only factor that correlated with the effect of rabeprazole on dysphagia was “improvement in heartburn symptoms.” There were no relapses of symptoms during the 6-month follow-up period, and pH monitoring showed sustained suppression of acid secretion.The results indicate that rabeprazole is effective in the treatment of dysphagia associated with gastroesophageal reflux disease. We were, however, unable to elicit any factors that could predict the therapeutic effect of rabeprazole before commencing treatment.

Five biopsy specimens from the proximal part of the tumor reliably determine HER2 protein expression status in gastric cancer

BackgroundNational guidelines recommend trastuzumab for treatment of patients with metastatic HER2-positive gastric cancer (GC). There is currently no guideline indicating the number of biopsy specimens and the location from which they should be obtained to reliably determine the human epidermal growth factor receptorxa02 (HER2) status in GC. The aim of this pilot study was (a) to quantify HER2-positive tumor cells in different tumor regions to assess the spatial heterogeneity of HER2 expression and (b) to establish the required number of biopsy specimens and the location from which they should be obtained within the tumor to achieve concordance between HER2 expression status in the biopsy specimens and the resection specimen.MethodsHER2 expression was quantified in six different regions of 24 HER2-positive GC and in six virtual biopsy specimens from different luminal regions. Intratumoral regional heterogeneity and concordance between HER2 status in the biopsy specimens and the resection specimen were analyzed.ResultsHER2-positive cells were more frequent in the luminal tumor surface compared with deeper layers (pxa0<xa00.001). GCs with differentiated histological features were more commonly HER2 positive (pxa0<xa00.001). Assessment of HER2 expression status in five biopsy specimens was sufficient to achieve 100xa0% concordance between the biopsy specimens and the resection specimen.ConclusionsThis is the first study to suggest preferential HER2 positivity at the luminal surface in GC and to establish a minimum number of biopsy specimens needed to obtain a biopsy HER2 result which is identical to that from the whole tumor. Our study suggests that HER2 testing in five tumor-containing endoscopic biopsy specimens from the proximal (oral) part of the tumor is advisable. The results from this pilot study require validation in a prospective study.

Enzyme-linked immunosorbent assay of nicotine metabolites

IntroductionThe level of cotinine in biological specimens, such as serum, urine, and saliva, measured by gas or liquid chromatography is the most validated and reliable indicator of exposure to tobacco smoke. However, chromatographic methods are not always suitable for all types of situations.MethodsWe validated a commercially available enzyme-linked immunosorbent assay (ELISA) that uses a polyclonal antibody to cotinine as a practical alternative to chromatographic methods.ResultsThe cotinine antibody cross-reacts to 3-hydroxycotinine (3HC) and its glucuronide, thus generating a value for immunoreactive (IR) cotinine, which is a complex comprising cotinine, 3HC, and 3HC-glucuronide. The levels of IR cotinine in the urine of kindergarten children closely correlated with those of cotinine measured by gas chromatography–mass spectrometry (GC–MS) and reflected the smoking behavior of their parents more precisely than cotinine levels determined by GC–MS.DiscussionOur findings showed that the cotinine-based ELISA can be a practical biomarker of exposure to tobacco smoke.