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

BACKGROUND AND AIMS: 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.

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 > or =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.

Weak response of helicobacter pylori antibody is high risk for gastric cancer: a cross-sectional study of 10,234 endoscoped Japanese.

BACKGROUND: A large number of endoscoped members of the general Japanese population were surveyed to investigate the relationship between Helicobacter pylori infection and gastric cancer. Special attention was given to antibody titer and age of the subjects. METHODS: We performed gastrointestinal endoscopy and measured serum anti-H. pylori antibody in 10,234 consecutive Japanese who participated in a health examination program. Gastric cancer, when suspected, was confirmed by histology. We graded the H. pylori antibody titer into three groups in accordance with optical density values by ELISA: 'strongly positive', 'weakly positive', and 'negative'. RESULTS: Among the 10,234 subjects (men/women, 7.021/3,213; mean age, 49.1 years), 4,909 (48%) were strongly positive, 1,750 (17%) were weakly positive, and 3,575 (35%) were negative for H. pylori antibody. Thirty-seven cases of gastric cancer were found among the 10,234 subjects (0.36%); 23/4,909 (0.47%) in the strongly positive group, 9/1,750 (0.51%) in the weakly positive group, and 5/3,575 (0.14%) in the negative group. Both the strongly and weakly positive groups showed a higher risk of gastric cancer than the negative group. In the subjects over age 60, the weakly positive group seemed to show the highest risk for gastric cancer. CONCLUSIONS: In this investigation of 10,234 Japanese, based on endoscopy results, those with serum H. pylori antibody had an increased risk for gastric cancer, while those 'weakly positive' showed a high risk, particularly in the elderly.

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 for H 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.

Assessment of gastric carcinoma risk associated with Helicobacter pylori may vary depending on the antigen used: CagA specific enzyme-linked immunoadsorbent assay (ELISA) versus commercially available H. pylori ELISAs.

BACKGROUND: Previous epidemiologic studies produced inconsistent results when examining the relation between Helicobacter pylori infection and the risk of gastric carcinoma by measuring various anti-H. pylori antibodies. This study investigated the increased risk of cancer by examining different antibodies, including the specific anti-CagA antibody and antibodies from two commercially available kits. METHODS: An ELISA for the detection of serum anti-CagA was established using a recombinant CagA protein that the authors previously reported. Serum anti-CagA titer was determined for 80 patients with gastric carcinoma and 80 gender- and age-matched controls. Two anti-H. pylori antibodies from the commercially available kits HEL-p (Amrad, Kew Vic, Australia) and HM-CAP (Enteric Product Inc., Westbury, NY) were also evaluated. RESULTS: Anti-CagA seropositivity differed significantly between gastric carcinoma patients and controls (92.5% vs. 55.0%; P = 0. 0001), showing an odds ratio of 10.4 (95% confidence interval [CI]: 4.23-29.74). The difference was less prominent for the seropositivity of HEL-p (77.5% vs. 58.8%; P = 0.0139; odds ratio: 2. 38; 95% CI: 1.20-4.82) and insignificant for that of HM-CAP (65.0% vs. 57.5%; P = 0.4325; odds ratio: 1.30; 95% CI: 0.68-2.49). CONCLUSIONS: The current study revealed that the antibody assay system used could be one important factor in the assessment of gastric carcinoma risk for patients with H. pylori.

[Epidemiological evaluation of the protective effect for dying of stomach cancer by screening programme for stomach cancer with applying a method of case-control study--a study of a efficient screening programme for stomach cancer].

An epidemiological evaluation of the protective effect for dying of stomach cancer by screening programme for stomach cancer was conducted with applying a method of case-control study. And also in order to carry out an efficient screening programme, the age groups who should be intensively recommended to receive screening and an optimal screening time interval since the last test were analyzed. 527 cases of men and 273 of women, dying of stomach cancer in the years 1981-1989 in the Awa region of Chiba prefecture, were identified from Chiba Cancer Registry. For each case, 3 controls were drawn at random from Awa living residents (about 162000 inhabitants at 1989 national census), with being matched strictly according to the district of residence, sex and born within 3 years of birth-year. For both cases and controls, the information about the screening history until the date of diagnosis of the case in each matched set was collected respectively from comparison with the screening certification. The results showed a relative risk of 0.417 (99% CI 0.284-0.612) in ever screened men compared with never screened and 0.480 (99% CI 0.280-0.823) in women. The significant reduction in risk was intensively observed on age groups 40-74 years among men and 50-69 years among women and the protective effect continued at most in the following three years since last screening. For an efficiency of screening programme, these age groups should be intensively recommended to receive screening and it is allowable that an optimal screening time interval since last negative test is at most 3 years for general attendance.

Phosphorus-31 nuclear magnetic resonance in vivo spectroscopy of human liver during hepatitis A virus infection.

To evaluate the changes in hepatocellular phospholipid metabolism during hepatitis virus infection, 26 patients with acute viral hepatitis A were studied by means of phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. The spectroscopy of liver showed six signal components in all patients as well as in the normal volunteers. During the early phase of illness, the phosphomonoester (PME)-phosphodiester (PDE) ratios in the patients became markedly greater than the ratios in the controls (P < 0.001). Within six weeks after the onset, the PME/PDE ratios returned to the level of controls. The time course analysis indicated an inverse correlation between the PME/PDE ratio and the period of time after onset (r = 0.738, P < 0.001). The spectral changes of human liver observed in acute viral hepatitis A are similar to those in the regenerating rat liver, indicating that 31P-NMR spectroscopy allows a noninvasive study of cell turnover in human liver disease associated with acute virus infection.

Neuropathologic study on chronic neurotoxicity of 5-fluorouracil and its masked compounds in dogs.

5-Fluorouracil (FU) and its masked compounds tegafur (FT) and carmofur (HCFU) were administered orally to Beagle dogs daily for 6 months, and their chronic neurotoxic effects were examined morphologically. In ten dogs that survived the 6-month treatment large vacuoles produced by splitting of the intraperiod line of myelin were observed in the fornix in the wall of the third ventricle. In severely affected dogs large vacuoles developed in the medial preoptic area, medial portion of the internal capsule, the area around the subthalamic nucleus and the mammillo-thalamic tract. Axons of myelinated fibers affected by vacuolation were generally well maintained, and destruction of myelin was not detected. Though proliferation of glia cells or abnormality of oligodendroglia was not detected, a lipid deposit covered by a single layer membrane was observed in the cell bodies and processes of astrocytes. No abnormality was detected by electron microscopy in the cerebrum, inferior colliculus, cerebellum, or pons. Of eight dogs that died during the treatment period, large vacuoles were observed in the fornix in the wall of the third ventricle of four dogs treated for more than 1 month, and large vacuoles were present in the inferior colliculus in two dogs of the FT group in the above four dogs. In the HCFU group, the interruption of treatment for 6 months resulted in alleviation or disappearance of the vacuolar lesions. The above findings suggest that the neurotoxicity of FU and its masked compounds FT and HCFU in long-term treatment produces changes morphologically identical with one another in respect to the site of their manifestation and nature of lesion, that their common degraded product alpha-fluoro-beta-alanine (FBAL) plays a crucial role in their neurotoxic actions, and that vacuolar lesions, to which myelin was more vulnerable than neurons, can develop where the toxic substance readily deposits and accumulates.

[Psychopharmacological effects of flutazolam (MS-4101) (author's transl)].

Behavioral effects of Flutazolam (MS-4101), a new derivative of benzodiazepines, was investigated and compared with effects of diazepam in mice and rats. MS-4101 suppressed hyperemotionality in septal rats, fighting behavior in long-term isolated mice and pentylenetetrazol convulsion and potentiated thiopental sleep. These effects of MS-4101 were the same in potency as those of diazepam. MS-4101 was more potent than diazepam in reducing the spontaneous locomotor activity in the open-field test and potentiating the stimulant effect of methamphetamine on locomotor activity. On the other hand, suppression of hyperemotionality in O. B. rats, potentiation of ethanol-induced anesthesia, prevention of maximal electroshock, prevention of strychnine convulsin and muscle relaxant effect of MS-4101 were less potent than in the case of diazepam. MS-4101 had also an anticonflict effect, which was less potent than that seen with diazepam. Suppression of locomotor activity was potentiated by chronic administration of MS-4101, but disappeared with chronic administration of diazepam. MS-4101 inhibited considerably both scratching and head-twitch induced by mescaline in mice. Scratching was increased with small doses of diazepam and decreased with high doses. Head-twitch was decreased with small doses of diazepam and increased with high doses.