Yutaka Yamaji

Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study

Background and aim:Helicobacter pylori infection and gastric atrophy are both risk factors for gastric cancer. We aimed to elucidate the natural history of gastric cancer development according to H pylori infection and gastric atrophy status. Subjects and methods: A total of 9293 participants in a mass health appraisal programme were candidates for inclusion in the present prospective cohort study: 6983 subjects revisited the follow up programme. Subjects were classified into four groups according to serological status at initial endoscopy. Group A (n = 3324) had “normal” pepsinogen and were negative for H pylori antibody; group B (n = 2134) had “normal” pepsinogen and were positive for H pylori antibody; group C (n = 1082) had “atrophic” pepsinogen and were positive for H pylori antibody; and group D (n = 443) had “atrophic” pepsinogen and were negative for H pylori antibody. Incidence of gastric cancer was determined by annual endoscopic examination. Results: Mean duration of follow up was 4.7 years and the average number of endoscopic examinations was 5.1. The annual incidence of gastric cancer was 0.04% (95% confidence interval (CI) 0.02–0.09), 0.06% (0.03–0.13), 0.35% (0.23–0.57), and 0.60% (0.34–1.05) in groups A, B, C, and D, respectively. Hazard ratios compared with group A were 1.1 (95% CI 0.4–3.4), 6.0 (2.4–14.5), and 8.2 (3.2–21.5) in groups B, C, and D, respectively. Age, sex, and “group” significantly served as independent valuables by multivariate analysis. Conclusions: The combination of serum pepsinogen and anti-H pylori antibody provides a good predictive marker for the development of gastric cancer.

A Randomized Controlled Trial Evaluating the Usefulness of a Transparent Hood Attached to the Tip of the Colonoscope

OBJECTIVES:Considering the increasing demand for colonoscopy, auxiliary devices that could facilitate the examination would be useful. A hood attached to the tip of the colonoscope has been reported to be helpful in detecting and removing colorectal polyps. However, its usefulness in aiding scope intubation has not been fully evaluated.METHODS:Patients for colonoscopy between July 2004 and May 2005 in Tokyo University Hospital were enrolled to this randomized controlled trial, and assigned to colonoscopy with a transparent hood, a short hood, or no hood. Colonoscopies were conducted by trainees without sedation. The evaluated outcomes were cecal intubation rate, trainee intubation rate (cecal intubation within 15 min), cecal intubation time, and polyp detection rate.RESULTS:Enrolled 684 patients were randomly assigned to transparent hood (N = 221), short hood (N = 228), and no hood (N = 235) groups. The overall cecal intubation rate was 95.3% (652/684) and did not differ among the groups. The overall trainee intubation rate was 55.1% (377/684) and significantly higher in the transparent hood group than in the no hood group for female patients (60.7% vs 37.4%, P = 0.003). Cecal intubation time was 11.5, 13.5, and 14.0 min in the transparent, short, and no hood groups, respectively, and significantly shorter in the transparent hood group than in the no hood group among overall (P = 0.008), female (P = 0.001), and old (P = 0.04) patients. Polyp detection rate was higher in the transparent hood group than in the no hood group (49.3% vs 39.1%, P = 0.04).CONCLUSIONS:The transparent hood was useful in shortening the cecal intubation time especially in difficult cases.

Single-balloon versus double-balloon endoscopy for achieving total enteroscopy: a randomized, controlled trial

BACKGROUND Balloon endoscopy has been accepted as an effective tool for examining the small intestine. Two types of balloon endoscopy, single and double, are commercially available. The difference in performance between these 2 types of balloon endoscopy has not yet been elucidated. OBJECTIVE To compare the yield of single-balloon endoscopy (SBE) and double-balloon endoscopy (DBE). DESIGN Single-center, randomized, controlled trial. SETTING University hospital in Tokyo, Japan. PATIENTS Patients with suspected small-bowel disease. INTERVENTIONS SBE and DBE. MAIN OUTCOME MEASUREMENTS Outcomes were the total enteroscopy rate, diagnostic yield, complication rate, and clinical outcomes. Analysis was done by intent to treat. RESULTS The study started in April 2008 and was terminated in April 2010 because of an obvious disadvantage for the SBE group. Thirty-eight patients were enrolled in the study; 18 patients were assigned to the SBE group and 20 to the DBE group. The total enteroscopy rate was 0% in the SBE group and 57.1% in the DBE group (P = .002). In terms of complications, the DBE group had 1 patient with Mallory-Weiss syndrome, and the SBE group had 1 patient with hyperamylasemia. There was no difference in the overall diagnosis rate between the SBE and DBE groups (61.1% vs 50.0%, P = .49). There was no difference in therapeutic outcome between the SBE and DBE groups (27.8% vs 35.0%, P = .63). LIMITATIONS Relatively small number of study patients. CONCLUSIONS Total enteroscopy is more easily performed with DBE than with SBE.

Incidence and recurrence rates of colorectal adenomas estimated by annually repeated colonoscopies on asymptomatic Japanese

Background: Whereas high recurrence rates of colorectal adenomas after polypectomy are widely recognised, little is known of the natural incidence in those with no neoplastic lesions initially. It is also known that single colonoscopy has a significant miss rate. Aims: To elucidate the incidence and recurrence rates of colorectal neoplasms from a large cohort of asymptomatic Japanese patients on the basis of annually repeated colonoscopies. Methods: A total of 6225 subjects (4659 men and 1566 women) participating in an annual colonoscopic screening programme and completing three or more colonoscopies were analysed during the 14 year period between 1988 and 2002. Patients were divided into three groups according to the findings of the initial two colonoscopies: 4084 subjects with no neoplasm, 1818 with small adenomas <10 mm, and 323 with advanced lesions, including carcinoma in situ, severe dysplasia, or large adenomas ⩾10 mm. Mean age at the second colonoscopy was 48.8 years. Results: For all types of colorectal neoplasms, the incidence rate in those with no initial neoplasm was 7.2%/year whereas recurrence rates in those with small adenomas and advanced lesions were 19.3% and 22.9%/year, respectively. For advanced colorectal lesions, the incidence rate was 0.21%/year whereas recurrence rates in those with small adenomas and advanced lesions were 0.64% and 1.88%/year, respectively. Colorectal neoplasms were in general more likely to develop in males and older subjects. Conclusions: Although recurrence rates after polypectomy were elevated, the incidence rates in subjects with no neoplastic lesions initially were quite high.

Inverse background of Helicobacter pylori antibody and pepsinogen in reflux oesophagitis compared with gastric cancer: analysis of 5732 Japanese subjects

BACKGROUND The relationship between Helicobacter pylori and reflux oesophagitis remains controversial. AIMS To evaluate the relationship between H pylori and reflux oesophagitis in a large number of Japanese subjects. SUBJECTS A total of 5732 consecutive Japanese subjects during a health screening were enrolled. METHODS Gastrointestinal endoscopy was performed on all subjects. We simultaneously measured serum anti-H pylori antibody and pepsinogen as markers of H pylori infection together with gastric atrophy. The risk of reflux oesophagitis was evaluated in relation to these markers, and the results were compared with those of gastric cancer. RESULTS Reflux oesophagitis was found in 108 subjects. Both positivity forH pylori antibody (adjusted odds ratio (OR) 0.67 (95% confidence interval 0.45–1.0)) and “low” pepsinogen indicating gastric atrophy (OR 0.35 (0.18–0.68)) were negatively associated with reflux oesophagitis. After subjects were classified into four groups based on positivity or negativity for H pylori antibody and “low” pepsinogen, the prevalence of reflux oesophagitis showed a decreasing trend as H pylori induced gastric atrophy became more severe. The risk of gastric cancer showed an increasing trend, exactly the opposite to that of reflux oesophagitis. CONCLUSIONS Analysis of a large series of Japanese subjects revealed a decreasing prevalence of reflux oesophagitis in conjunction with progress of gastric atrophy induced by H pylori infection. This pattern was completely opposite to that of gastric cancer cases. A protective role of H pylori for reflux oesophagitis through the development of gastric atrophy has been suggested.

The effect of Helicobacter pylori eradication on reducing the incidence of gastric cancer.

Epidemiologically, the association between chronic Helicobacter pylori infection and development of gastric cancer is well established. Although the possibility of preventing gastric cancer by eradicating H. pylori infection was recently investigated by several research groups, the results remain controversial. The aim of this study was to determine whether the eradication of H. pylori infection would reduce the incidence of gastric cancer. In total, 304 patients with persistent H. pylori infection and 404 patients with H. pylori infection eradicated were examined annually for gastric cancer by endoscopy. Over an average of 3.1 years for the first group and 3.2 years for the second group, 13 and 6 patients, respectively, were diagnosed as having new gastric cancer. The cumulative incidence of gastric cancer was statistically different between the groups (P=0.019; log-rank test). The hazard ratio of H. pylori eradication was 0.335 by Cox proportional hazards model (P=0.047). Differentiated gastric cancer was found in 11 patients in the persistent infection group and 3 patients in the eradicated group. The incidence of differentiated cancer was significantly different (P=0.017) between the groups, but not for undifferentiated cancer (P=0.847). The results of the current study suggest that the eradication of H. pylori infection reduces the incidence of gastric cancer.

Helicobacter pylori Activates the Cyclin D1 Gene through Mitogen- Activated Protein Kinase Pathway in Gastric Cancer Cells

ABSTRACT Helicobacter pylori induces cellular proliferation in host cells, but the mechanism remains unclear. Thus, we examined the effect of H. pylori on cyclin D1, an important regulator of the cell cycle, especially in relation to intracellular signaling pathways. In a Northern blot analysis, cyclin D1 transcription in gastric cancer (AGS) cells was enhanced by coculture with H. pylori strain TN2 in a time-dependent and multiplicity-of-infection-dependent manner. An isogenic mutant form ofvacA also increased cyclin D1 transcription, but mutant forms of cagE or the entire cag pathogenicity island did not enhance cyclin D1 transcription. These effects were confirmed with a luciferase assay of the cyclin D1 promoter (pD1luc). Cyclin D1 promoter activation by H. pylori was inhibited by MEK inhibitors (U0126 and PD98059), indicating that the mitogen-activated protein kinase pathway may be involved in intracellular signal transduction. In contrast, transfection of a reporter plasmid having any point mutations of the NF-κB binding sites in the promoter (pD1-κB1M, pD1-κB2M, or pD1-κB1/2M) or cotransfection of dominant negative IκBα did not affect cyclin D1 activation by H. pylori. In conclusion, H. pylori activates cyclin D1 through the mitogen-activated protein kinase pathway and not through NF-κB activation in AGS cells. This activation of cyclin D1 is partly dependent on the cagpathogenicity island but not on vacA.

Sensitivity of immunochemical fecal occult blood test to small colorectal adenomas.

BACKGROUND:Although the immunochemical fecal occult blood test (FOBT) is reportedly more sensitive to large adenomas or colorectal cancer (CRC) than the guaiac-based FOBT, the sensitivity of the immunochemical FOBT to small adenomas has scarcely been reported. Previous reports have indicated that the guaiac-based FOBT can detect small adenomas only by serendipity.OBJECTIVES:To investigate the sensitivity of immunochemical FOBT to small adenomas using a large-scale cohort.METHODS:We analyzed 21,805 consecutively enrolled asymptomatic persons who underwent colonoscopy and immunochemical FOBT.RESULTS:The sensitivity to adenomas ≤9 mm was significantly higher than the false-positive rate as revealed by analysis of all eligible subjects (7.0% vs 4.5%, P < 0.001). In men, the sensitivity was superior to the false-positive rate and increased with age (<50 yr 6.1% and >60 yr 11.3%). On the other hand, the sensitivity in women was not significantly different from the false-positive rate in any generation (5.1% vs 4.7% for all eligible women, P = 0.72).CONCLUSIONS:Immunochemical FOBT detected a small percentage of small adenomas in men at a rate that is significantly higher than the false-positive rate. Studies comparing the guaiac and immunochemical FOBTs using the end point of CRC-related death are expected.

The Effect of Body Weight Reduction on the Incidence of Colorectal Adenoma

OBJECTIVES:Obesity is thought to be associated with colorectal cancer and adenoma. We aimed to investigate the effect of body weight on the risk of colorectal adenoma both in cross-sectional and longitudinal analyses.METHODS:This is a retrospective cohort study in a large-scale health appraisal institution in Japan. A total of 7,963 asymptomatic, average-risk Japanese were enrolled at initial examinations, and 2,568 subjects who underwent a second colonoscopy after 1 yr were investigated. The association with the prevalence of colorectal adenoma was evaluated according to the body mass index (BMI) at the initial examination. The incidence of colorectal adenoma at the second colonoscopy was investigated according to the initial BMI and body weight changes during the year.RESULTS:The prevalence of colorectal adenoma increased in relation to increases in the BMI: 15.4%, 20.6%, 22.7%, and 24.2%, respectively, in the first (BMI < 21.350), second (21.350 ≤ BMI < 23.199), third (23.199 ≤ BMI < 25.156), and fourth (25.156 ≤ BMI) quartiles. The adjusted odds ratios in reference to Group Q1 were 1.15 (95% CI 0.97–1.37, P= 0.1) for Group Q2, 1.19 (1.01–1.41, P= 0.04) for Group Q3, and 1.32 (1.12–1.56, P= 0.001) for Group Q4. The incidence rates of colorectal adenoma after 1 yr also increased proportionally according to the initial BMI: Group Q1 (12.9%), Group Q2 (15.7%), Group Q3 (18.3%), and Group Q4 (19.0%).CONCLUSIONS:Obesity was associated with the risk for colorectal adenoma, and body weight reduction was suggested to decrease this risk.

Endoscopic submucosal dissection is an effective and safe therapy for early gastric neoplasms: a multicenter feasible study.

Background and Aim: The technique of endoscopic submucosal dissection (ESD) was introduced to obtain en bloc specimens of large early gastrointestinal neoplasms. The drawback of ESD is its technical difficulty and, consequently, its higher rate of complication. In this multicenter study, we investigated the therapeutic outcomes of ESD in consecutive patients. Methods: From January 2002 to December 2008, 485 early gastric neoplasms in 418 patients were consecutively treated by using ESD procedure performed by 6 endoscopists in 4 institutions in Tokyo. Demorgraphics, tumor location, therapeutic outcomes, and complication rates were analyzed. Results: The rates of en bloc resection, complete en bloc resection, submucosal invasion, and piecemeal resection were 93.6%, 85.4%, 10.9%, and 5.4%, respectively. In multivariate analysis, the en bloc resection rate was independently lower in lesions in upper portion than in lower portion (P<0.01), lower in larger lesions (>30 mm, P<0.05; 20 to 30 mm, P<0.05), and lower in lesions with a scar (P<0.01). Delayed bleeding occurrence was independently high in larger lesions (>30 mm, P<0.01; 20 to 29 mm, P<0.01) than in small lesions (<20 mm). Institution and endoscopists were not risk factors of en bloc resection and complications Conclusions: ESD is an effective and safe therapy in the management of early gastric neoplasms when performed by well-trained endoscopists. Endoscopists should recognize the difficulty to perform ESD for en bloc resection of upper lesion, and the risk of delayed bleeding in cases of lesions >2 cm in size.