Nobutaka Yamada

Genetic differences in CYP2C19 single nucleotide polymorphisms among four Asian populations

Background. This study was designed to compare genetic differences in single-nucleotide polymorphisms of the S-mephenytoin 4′-hydroxylation (CYP2C19) gene among four Asian populations. Methods. Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) analysis of CYP2C19 was conducted in Japanese, Chinese, Thai, and Vietnamese populations. All genotype frequencies were analyzed. Wild-type homozygote and wild-type heterozygote genotypes were extensive proton pump inhibitor (PPI) metabolizers. Mutant-type heterozygote and mutant-type homozygote genotypes were poor PPI metabolizers. Results. No significant differences in CYP2C19 phenotype, calculated based on genotype frequencies, (P > 0.05) were found among the four populations. Conclusions. Many factors, including CYP2C19 polymorphisms, affect the success rate of Helicobacter pylori eradication with PPI-based therapy. We suspect that CYP2C19 polymorphisms may not be the main factor associated with differences among these four Asian populations in the success rates of H. pylori eradication with PPI-based therapy.

Helicobacter pylori Infection, Mucosal Atrophy and Intestinal Metaplasia in Asian Populations: A Comparative Study in Age-, Gender- and Endoscopic Diagnosis-Matched Subjects

Background. It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races.

Helicobacter pylori Infection in the Remnant Stomach After Gastrectomy: With Special Reference to the Difference Between Billroth I and II Anastomoses

Helicobacter pylori infection is associated with many gastric diseases, such as peptic ulcer and gastric cancer. We examined the remnant stomach for H. pylori infection after gastrectomy for gastric cancer or peptic ulcer between October 1992 and July 1997. H. pylori DNA in the gastric juice of 109 patients [mean age 62.4 years, male/female 78/31, gastrectomy for gastric cancer 83/peptic ulcer 26, Billroth I (BI) anastomosis 72/Billroth II (BII) 37, mean postoperative interval 6.0 years] was amplified by PCR and detected by Southern blot hybridization. The serum of 135 patients was assayed by ELISA for IgG antibody against H. pylori (mean age 61.8 years, male/female 99/36, gastrectomy for gastric cancer 111/peptic ulcer 24, BI anastomosis 93/BII 42, mean postoperative interval 5.4 years). H. pylori was positive in 68/109 (62.4%) by PCR and 113/ 135 (83.7%) by ELISA. H. pylori cytotoxin gene cagA, a H. pylori virulence factor gene, was found in 15/16 (93.8%) cases by PCR. A significant difference in H. pylori positivity by PCR was found according to the type of anastomosis (BI vs. BII) but not according to age group, sex, disease (cancer or ulcer), or postoperative interval by PCR and ELISA. BII anastomosis was followed by a significantly lower rate of H. pylori infection (17/37; 45.9%) than BI anastomosis (51/72; 70.8%; p=0.01) according to the results of PCR. Moreover, some patients with BII anastomosis (3/8; 37.5%) showed positive to negative seroconversion for H. pylori infection after the operation (mean 2.47 years) according to the results of ELISA, but this phenomenon was not observed in patients with BI (0/12) anastomosis. This may reflect the role of bile reflux, which is more common in BII than BI, because bile reflux interferes with colonization by H. pylori.

Topography of chronic active gastritis in Helicobacter pylori-positive Asian populations : age-, gender-, and endoscopic diagnosis-matched study

BackgroundThe incidence and mortality of gastric cancer is high among Japanese and Chinese populations but extremely low in Thailand and low in Vietnam. The aim of this study was to compare the degree of corpus-predominant gastritis, which is considered to be one of risk factors of gastric cancer, in Helicobacter pylori-positive Asian adult populations.MethodsH. pylori-positive Chinese (Beijing and Fuzhou), Thai, and Vietnamese patients were paired with Japanese patients by age, gender, and endoscopic diagnosis to compare the ratio of corpus gastritis to antrum gastritis (C/A ratio) (105, 85, 195, and 154 pairs, respectively).ResultsThe Japanese C/A ratio was significantly higher than that in other groups. Corpus-predominant gastritis (C/A ratio > 1.00) was characteristic in aged Japanese and Chinese (Fuzhou), but Chinese (Beijing), Thai, and Vietnamese were antrum predominant (C/A ratio < 1.00) in every age group except for the Vietnamese over-70 group. There was a similarity between degree of H. pylori colonization and neutrophil activity score.ConclusionsCorpus-predominant gastritis was found in aged Japanese and Chinese (Fuzhou) and antrum-predominant gastritis was found in Chinese (Beijing), Thai, and Vietnamese patients. These results correlate with the low incidence of gastric cancer in Thai and Vietnamese populations.

Helicobacter pylori eradication therapy for the remnant stomach after gastrectomy.

Background.The remnant stomach after surgery for gastric cancer is at high risk for the metachronous development of multiple gastric cancers. Here, we report on eradication therapy of Helicobacter pylori in the remnant stomach, comparing the eradication rate with that in unoperated stomachs. We examined gross and histological changes after treatment. Methods. Forty H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based dual and triple therapies. After eradication, histological changes were classified on the basis of the updated Sydney system. Results. The eradication rate in the remnant stomach was 70% (14 of 20) after dual therapy and 90% (18 of 20) after triple therapy, using per-protocol analysis, and these rates were comparable to the rates of 70% (186 of 264) and 88% (58 of 66), respectively, in nonsurgery patients. After eradication, three sites in the remnant stomach showed similar histological changes: significant decreases in inflammation and activity scores (P < 0.001) and no significant changes in glandular atrophy and intestinal metaplasia scores. Conclusion. PPI-based therapy was as effective for H. pylori eradication in the remnant stomach as in the unoperated stomach, and eradication therapy resulted in a significant decrease in inflammatory cell infiltration of the mucosal layer.

Ossifying fibromyxoid tumor of soft parts : Clinicopathologic, immunohistochemical and ultrastructural study of four cases

Four cases of uncommon soft tissue tumors were investigated histopathologically. All of them consisted of fibrous and myxoid components, and mature bone showed shell‐like characteristics. Histological features revealed these tumors were well circumscribed by a thick collagenous fibrous capsule and composed of uniform‐sized fusiform cells with eosinophilic cytoplasm and a round or oval nucleus in the myxoid matrix. An incomplete shell of mature bone with lamellar structure was also observed at the periphery. Immunohistochemical and ultrastructural studies were performed. The major component of the proliferating cells in the tumors had positive staining for vimentin, S‐100 protein, neuron‐specific enolase and synaptophysin. The myxoid matrix was stained by alcian blue and was digested completely by pretreatment with hyaluronidase. Electron microscopy showed the cytoplasm contained dense‐core granules measuring 100–200 nm and abundant filaments of an intermediate size. It is suggested that these uncommon tumors might be diagnosed as the ‘ossifying fibromyxoid tumor of soft parts’ previously described by Enzinger et al., which were derived from peripheral nerve sheath tumors such as neurofibroma and myxoid neurofibroma.

Gastrospirillum hominis and Helicobacter pylori infection in Thai individuals: Comparison of histopathological changes of gastric mucosa

The presence of Helicobacter pylori (H. pylori) in the stomach is closely associated with histological signs of chronic active gastritis and peptic ulcer. Another spiral organism named Gastrospirillum hominis (G. hominis) has led to further interest in the bacterial pathogenesis of gastritis. Due to the low prevalence of G. hominis, it is difficult to evaluate its biological behavior. Recently 16 cases of G. hominis‐associated gastritis were found in 257 Thai individuals, which made it possible to study the biological characteristics of G. hominis and its relationship with gastric mucosal inflammation. The results showed that H. pylori and G. hominis could be easily observed in the lower third of the mucous layer and in the mucosa of the gastric pits by means of toluidlne blue staining. Both bacteria immunostained positive. Helicobacter pylori were usually in the shape of curved bacillary while G. hominis often appeared in spiral configuration. In 257 cases of Thai subjects, 169 cases were found to be H. pylori positive, the detection rate was 65.7%, and 16 cases were G. hominis positive, with a 6.2% detection rate. In G. hominis infection, 43.6% of cases had normal gastric mucosa. Superficial, erosive and atrophlc gastritis cases were 13.2, 10.9 and 12.5%, respectively. Mucosal inflammation was usually severe in H. pylori, but neutrophil polymorph infiltration was often mild and focal in G. hominis Infection. Although no G. hominis infection with carcinoma was shown in our cases, the occurrence of mucosal atrophy, metaplasia and dysplasia was higher in both bacterial infections compared with H. pylori‐ and G. hominis‐negative cases. It is suggested that G. hominis may be partly responsible for the mucosal inflammation and some malignant‐associated lesions.

Inflammation of the gastric remnant after gastrectomy: mucosal erythema is associated with bile reflux and inflammatory cellular infiltration is associated with Helicobacter pylori infection

BackgroundControversy exists concerning the role of bile reflux and Helicobacter pylori (H. pylori) infection in the development of inflammation of the gastric remnant after gastrectomy. This study was designed to investigate association of bile reflux and H. pylori infection or both with inflammatory changes in the gastric remnant.MethodsA questionnaire on GI symptoms was returned by 200 gastrectomy patients, and 24-h bilirubin monitoring in the gastric remnant was performed on 55 patients with Bilitec 2000. Upper GI endoscopy evaluated reflux gastritis in the gastric remnant, and the presence of H. pylori infection and chronic, active inflammatory cellular infiltration in the biopsy specimens were examined microscopically with the updated Sydney system.ResultsNo difference in the incidence of GI symptoms was observed among individual gastrectomy patients. Bile reflux was lower in patients who had undergone a gastrectomy with jejunal interposition, a pylorus-preserving gastrectomy, and a gastrectomy with Roux–Y anastomosis than those who had undergone a Billroth-II (B-II) anastomosis (P < 0.05). Endoscopy showed positive correlation between mucosal erythema and bile reflux (P < 0.001). No correlation was observed between the mucosal erythema and chronic and active inflammatory cellular infiltration. Infection of H. pylori correlated with chronic and active inflammatory cellular infiltration (P < 0.001). Bile reflux did not correlate with the severity of chronic and active inflammatory cellular infiltration or H. pylori infection.ConclusionsBile reflux into the gastric remnant was observed by Bilitec 2000. Mucosal erythema and chronic, active inflammatory cell infiltration in the gastric remnant after gastrectomy may be caused by bile reflux or H. pylori infection, respectively.

Gastrointestinal autonomic nerve tumors: Immunohistochemical and ultrastructural studies in cases of gastrointestinal stromal tumor

The gastrolntestlnal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor with a morphological feature resembling the cell processes of the enteric plexus, and was originally teimed a plexoma or plexosarcoma. Light microscoplc studies show the GAN tumor most often consists of spindle‐shaped cells indistinguishable from a smooth muscle tumor or Schwann cell tumor. Immunohistochemical and ultrastructural examinations of 18 cases of gastrointestinal stromal tumor (GIST) were performed. During ultrastructural examination, all of the 12 cases which were immunohisto‐chemically positive for S‐100 protein or neuron‐specific eno‐lase (NSE) showed synapse‐like structures containing dense core neurosecretory granules measuring 100–200 nm, and 40–60 nm endocytoplasmic vesicles. These results suggest that most GIST of neurogenlc origln are tumors derived from the myenteric nerve plexus.

Sex differences in mucosal response to Helicobacter pylori infection in the stomach and variations in interleukin‐8, COX‐2 and trefoil factor family 1 gene expression

Background : Gastric cancer incidence in men is almost double that in women. We investigated mucosal responses in the stomach against Helicobacter pylori (H. pylori) infections to elucidate the interindividual or sex‐related differences, which may in turn be associated with gastric cancer incidence, mucosal changes of stomach as measured by the Sydney System, and interleukin‐8, cyclooxygenase‐2 and trefoil factor family 1 (TFF1) gene expression.