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Biomedical subjects

Ken Haruma

Publications and source records attributed to Ken Haruma.

89 records · Page 5Linked to original sources
PubMed2002

Clinical characteristics and natural history of patients with low-grade reflux esophagitis.

BACKGROUND AND AIM: Although the incidence of reflux esophagitis (RE) has recently increased in Japan, the majority of these cases are mild (Los Angeles classification grades A and B). In order to consider therapy for these patients, it is important to understand the natural history of mild RE. There is little information concerning the natural course of RE, particularly low-grade disease. The goal of this study is to elucidate the natural course of patients with mild RE and to identify specific prognostic indicators associated with a poor outcome. METHODS: One hundred and five patients with mild RE were followed, without medical treatment, by endoscopy in addition to a questionnaire regarding symptomatology, for a mean of 5.5 years (range, 2.0-8.8 years) after initial diagnosis. Factors associated with the development of severe esophagitis were analyzed. RESULTS: Endoscopically, 11 patients (10.5%) progressed to more severe forms of RE (recurrent progressive (RP) group), 60.0% of patients relapsed without disease progression (recurrent non-progression group), and the remaining 29.5% of patients had no further episodes of RE (isolated episode group). Risk factors for progressive disease were increased age, female sex, the presence of symptoms at initial diagnosis by endoscopy, presence of a hiatal hernia, absence of atrophic gastritis, and absence of Helicobacter pylori infection. Despite having all risk factors, there were six patients who did not progress to more severe forms of RE. The primary esophageal peristaltic amplitude in these patients was significantly higher than in the RP group. CONCLUSIONS: Among patients with mild RE, only 10.5% progressed to more severe forms of RE. The patients with risk factors are candidates for aggressive therapy in order to prevent the progression of the RE disease process.

Aged↗
PubMed2002

Helicobacter pylori infection increases serum nitrate and nitrite more prominently than serum pepsinogens.

BACKGROUND: Helicobacter pylori infection causes chronic gastritis and results in increased serum concentrations of pepsinogens I and II as well as gastrin, while the ratio of pepsinogen I to II (I : II) is decreased. Inducible nitric oxide synthase (iNOS) is induced in H. pylori-associated gastritis and may modulate inflammation. However serum nitrate and nitrite (NOx) concentrations in patients with H. pylori-induced chronic gastritis have not been reported. We examined differences in serum NOx between H. pylori-negative and positive volunteers relative to differences in pepsinogens and gastrin. MATERIALS AND METHODS: Sera from 80 healthy asymptomatic volunteers younger than 36 years were analyzed for anti-H. pylori antibody, NOx, gastrin and pepsinogens. RESULTS: In H. pylori antibody-positive subjects serum NOx concentrations were higher than in negative subjects (p < .005). In H. pylori-negative subjects, NOx correlated with pepsinogen II (r = .405, p < .05). In subjects with low pepsinogen I or II, NOx was higher in H. pylori-positive than negative subjects (p < .001). In subjects with high pepsinogen I : II (6 or higher), serum NOx was higher in H. pylori-positive than in negative subjects. CONCLUSIONS: H. pylori-induced gastritis increases serum NOx concentrations more prominently than those of pepsinogen. In H. pylori-negative subjects, serum correlates with serum pepsinogen II.

Adult↗
PubMed2002

Serological comparison of serum pepsinogen and anti-parietal cell antibody levels between Japanese and German patients.

BACKGROUND: Atrophic gastritis is more common in Japan than in Germany. The expression of anti-parietal cell antibody has been implicated in the genesis of atrophic gastritis associated with Helicobacter pylori infection. OBJECTIVE: We investigated the difference in serum levels of pepsinogens and in anti-parietal cell antibody expression between Japanese and German patients. METHODS: We recruited 102 Japanese and 46 German patients with dyspepsia. Endoscopic examination detected no localized lesions in the upper gastrointestinal tract of any patients. Anti-parietal cell antibody was investigated by enzyme-linked immunosorbent assay with the purified porcine H+,K+-ATPase fraction and immunohistochemistry. H. pylori infection was diagnosed by the presence of anti-H. pylori antibody, by using the urease test and by histological examination. Serum levels of pepsinogen I and II and of gastrin were measured by a modified radioimmunoassay. RESULTS: Seventy-one Japanese (70%) and 17 Germans (37%) were positive for H. pylori. Serum levels of anti-parietal cell antibody were not significantly different between Japanese and Germans in both H. pylori negative and positive groups. The serum pepsinogen I/II ratio and gastrin levels were altered by H. pylori infection in both populations. Moreover, anti-parietal cell antibody levels were higher in H. pylori-positive patients with low pepsinogen levels than in those with high pepsinogen levels in both populations. CONCLUSIONS: The levels of anti-parietal cell antibody do not differ statistically between Japanese and Germans. Anti-parietal cell antibody might play a role in the progression of atrophic gastritis in both Japanese and German patients.

Adolescent↗
PubMed2002

Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma.

AIM: Vascular endothelial growth factor C (VEGF-C) is known to be associated with the development of the lymphatic vascular system. The aim of this study was to elucidate the clinical significance of VEGF-C expression and microvessel density (MVD) at the deepest invasive site in advanced colorectal carcinoma (CRC). METHODS: 152 patients who had undergone surgical resection for advanced CRC entered this study. VEGF-C expression was examined immunohistochemically with anti-VEGF-C polyclonal antibody C-20. Tumor MVD was determined immunohistochemically with anti-CD34 antibody. VEGF-C expression was defined as positive if distinct staining of the cytoplasm was observed in at least 10% of tumor cells at the deepest invasive site, central portion and superficial part of the tumor. MVD was estimated by averaging the count of three x400 fields in the most vascular area at the deepest invasive site. RESULTS: VEGF-C expression was detected in 71 of 152 lesions (46.7%) at the deepest invasive site. VEGF-C expression correlated significantly with poorer histologic grade, depth of invasion, lymphatic invasion, lymph node metastasis, venous invasion, liver metastasis and Duke's stage. At the central portion and superficial part, there were no significant differences between VEGF-C expression and clinicopathological findings. VEGF-C expression at the deepest invasive site also correlated significantly with MVD. In cases with curative surgery, patients with VEGF-C expression at the deepest invasive site had a significantly poorer prognosis than those without VEGF-C expression. Furthermore, prognosis for patients with both VEGF-C expression and high MVD at the deepest invasive site was significantly poorer than that of patients without VEGF-C expression and with low MVD. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF-C expression were significant risk factors. CONCLUSION: VEGF-C expression at the deepest site of tumor invasion can be a useful predictor of poor prognosis in advanced CRC and show a close relation to angiogenesis.

Aged↗
PubMedDate not supplied

Clinicopathologic features and endoscopic resection of early primary nonampullary duodenal carcinoma.

Early primary nonampullary duodenal carcinoma is an extremely rare disease with poorly defined clinicopathologic features; early detection of this carcinoma is not common. To clarify the clinicopathologic characteristics of early primary nonampullary duodenal carcinoma and retrospectively analyze methods of treatment. Seventeen early duodenal carcinomas identified between 1994 and 2001 in 15 patients were studied. Lesions were divided into 2 groups: sporadic carcinoma (10 cases in 10 patients) and familial adenomatous polyposis associated carcinoma (7 cases in 5 patients). Clinicopathologic features and methods of treatment were compared between groups. The mean age of patients with sporadic carcinoma (63.8 years) was significantly higher than that of patients with FAP-associated carcinoma (34.9 years). The incidence of sporadic carcinoma was significantly higher in men that in women (M:F ratio 9:1); the difference between sexes in the incidence of FAP-associated carcinoma (1:4) was not significant. There was no significant difference between both groups in relation to tumor size, location, gross appearance, or histopathology. Thirteen of the duodenal tumors were treated by endoscopic mucosal resection (EMR), two by polypectomy, and two by open surgery. Complications were encountered in 1 of 15 cases (6%); local bleeding occurred after one EMR, but hemostasis was achieved endoscopically. The mean follow-up period for all patients was 51.7 months. No patients experienced recurrence after resection. The significant differences between patients with sporadic and those with early FAP-associated duodenal carcinoma were in age and sex. Endoscopic resection appears to be a safe and efficient treatment of carefully selected patients with early primary nonampullary duodenal carcinoma.

Adenomatous Polyposis Coli↗
PubMedDate not supplied

Angiogenesis in advanced colorectal adenocarcinoma with special reference to tumoral invasion.

BACKGROUND: Angiogenesis is a crucial step in tumor growth and progression. Its quantification by microvessel counting has a prognostic value in several types of malignancies and recently has been appraised in gastrointestinal tumors. AIM: To assess the prognostic significance of microvessel quantification in colorectal carcinomas, studying its association with hematogenous metastases, survival and clinicopathological variables such as size, histologic differentiation and depth of tumoral invasion. PATIENTS/METHODS: Forty eight patients with colorectal adenocarcinoma were included in this study. Histologic sections of invasion tumoral margin (4 microns) were analyzed and endothelined microvessels were immunostained with monoclonal mouse Von Willebrand Factor (anti-FVIII). The microvessel count was performed from the identification of the area with increased microvessel density--hot spots--and results of the mean in five of these fields. RESULTS: The cut-off microvessel count was 14 microvessels/0.785 mm2, which divided the sample into hypovascular and hypervascular groups. While 2/8 (25%) tumors with muscularis propria invasion were classified as hypervascular, 11/15 (73%) tumors with serosa or perivisceral fat were classified as hypervascular. However, a non-significant statistical association was found between the angiogenesis quantification, hematogenous metastases, survival and clinicopathological variables such as size and histologic differentiation of the tumor. CONCLUSIONS: The findings of significantly increase of microvessel count in conformity with tumoral invasion depth supports the hypothesis that tumor progression might be related to angiogenesis. Although angiogenesis is an important step in the tumoral growth and during the metastatization process, other factors can be implicated.

Adenocarcinoma↗
PubMedDate not supplied

Clinical significance of angiogenesis in rectal carcinoid tumors.

This study was designed to examine angiogenesis in rectal carcinoid tumors in relation to the clinicopathologic features. Seventy-seven rectal carcinoid tumors were studied clinicopathologically and experimentally. Cellular proliferation and microvessel density (MVD) were examined immunohistochemically. We used the antibodies MIB-1 for Ki-67, DO7 for p53, and NU-4A1 for CD34 expression in this study. Ki-67 labeling index (LI) of all lesions was below 3%, and the median Ki-67 LI of all lesions was 0.68+/-0.70% (mean +/- SD). A correlation was recognized between tumor size, metastasis and Ki-67 LI (p<0.05). Median MVD of all lesions was 25.9+/-13.1 (mean +/- SD). MVD was correlated with the tumor size (p<0.01), presence of depression (p<0.01), lymphatic (p<0.01) or venous (p<0.05) invasion, and existence of metastasis (p<0.01). But there was no significant relationship between MVD and Ki-67 LI. p53 protein was detected sporadically in only 1 case (1.3%) demonstrating both liver and lymph node metastases. Rectal carcinoid tumors are slow-growing tumors with a lower proliferative activity. Angiogenesis plays an important role in progression of rectal carcinoid tumors independent of the cellular proliferative activity.

Antigens, CD34↗
PubMedDate not supplied

Determining depth of invasion by VN pit pattern analysis in submucosal colorectal carcinoma.

The aim of this study was to clarify whether the pit pattern on the surface of submucosal colorectal carcinoma is associated with level of invasion. We examined the VN pit-pattern (loss or decrease of pits with an amorphous structure) area of the tumor surface in 18 submucosal carcinomas that were classified based on gross appearance as either superficial or broad based sessile polypoid tumors. Pit pattern determination was made according to a previously reported system. We then evaluated the relation between the VN pit-pattern area, the maximum diameter of the VN pit-pattern area obtained stereoscopically after resection, and the depth of submucosal invasion. There was a significant correlation between the area and maximum diameter of the VN pit-pattern segment. There was also significant correlation between the maximum diameter of the VN pit-pattern area and the depth of submucosal invasion. Lesions with a maximum VN pit-pattern area diameter <5 mm showed a depth of submucosal invasion of <1500 microm. In submucosal colorectal carcinoma of the superficial or broad based sessile polypoid type in gross appearance, measurement of the maximum VN pit-pattern area diameter allows estimation of the depth of submucosal invasion.

Carcinoma↗
PubMedDate not supplied

Hypoxia-inducible factor-1alpha expression and angiogenesis in gastrointestinal stromal tumor of the stomach.

Hypoxia inducible factor (HIF)-1 is reported to transactivate expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor. The aim of this study was to elucidate the clinical significance of HIF-1alpha expression in gastrointestinal stromal tumors (GIST). Specimens obtained from 53 patients who underwent surgical resection for GIST of the stomach were used in this study. Specimens were examined immunohistochemically for HIF-1alpha, VEGF, and Ki-67 expression. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD31 antibody and was estimated by averaging the counts from three high-power fields in the area showing the greatest neovascularization. HIF-1alpha expression was detected in 17 (32.1%) of 53 lesions and was correlated significantly with tumor size, liver metastasis, VEGF expression, and MVD. Prognosis was significantly poorer in patients with tumors expressing HIF-1alpha than in patients with tumors lacking HIF-1alpha expression. HIF-1alpha may play a role in angiogenesis and tumor progression of GIST through regulation of VEGF.

Adult↗
PubMedDate not supplied

Frequent loss of heterozygosity on chromosome 10p15, a putative telomerase repressor/senescence gene locus, in gastric cancer.

Previous studies suggest that a telomerase repressor/senescence gene, which acts as a tumor suppressor gene, may be located on chromosome 10p15. However, there are no studies on alterations on chromosome 10p15 in gastric cancers. We, therefore, examined loss of heterozygosity (LOH) on the 10p15 in gastric cancers by microsatellite assay. Two microsatellite loci, D10S501 and D10S602, were used. Fifty-seven gastric cancers, including 36 intestinal type and 21 diffuse type, were selected. LOH at D10S602 and D10S501 was detected in 6 of 18 (33%) and 5 of 27 (19%) gastric cancers, respectively. There was no significant correlation between LOH at these loci and clinicopathologic features, including patient age, sex, tumor location, histologic subtype, depth of invasion, and lymph node metastasis. These data suggest that a putative telomerase repressor/senescence gene may be located on chromosome 10p15, especially at the D10S602, in gastric carcinogenesis, and that the putative gene malfunction may be involved in the early stages of gastric carcinogenesis.

Adult↗
PubMedDate not supplied

Somatic mutation in mitochondrial DNA and nuclear microsatellite instability in gastric cancer.

It was reported that somatic mutations in the mitochondrial DNA (mtDNA) are associated with high-frequency microsatellite instability (MSI-H) of the nuclear in gastric cancers. However, no correlation between mtDNA mutations and nuclear MSI-H was found in colorectal, breast, and renal cancers. Therefore, the association between mtDNA mutations and nuclear MSI-H in gastric cancers is controversial. We examined mtDNA mutations and nuclear MSI in a large panel of gastric cancers. One-hundred and five gastric cancers were selected. Mutations in the mononucleotide repeat (D310) of mtDNA and nuclear MSI at 5 microsatellite loci were examined by microsatellite assay. Somatic mutations in the mtDNA and nuclear MSI-H were detected in 16 (15%) and 14 (13%) of the gastric cancers, respectively. mtDNA mutations were detected in 2 of the 14 (14%) and 14 of the 91 (15%) tumors with and without nuclear MSI-H, respectively. There was no significant difference between them. These results suggest that somatic mutations in the mtDNA and nuclear MSI-H play important roles in gastric carcinogenesis, and that mtDNA mutations may not be associated with nuclear MSI-H in gastric cancers.

Adult↗
PubMedDate not supplied

Evaluation of an ELISA for detection of anti-parietal cell antibody.

BACKGROUND/AIMS: Anti-parietal cell antibody (APCA) is used for diagnosis of pernicious anemia and type A gastritis. APCA is present in patients with Helicobacter pylori (H. pylori)-positive gastritis and is related to atrophic gastritis and gastric carcinoma. The aim of the study was to determine whether an enzyme-linked immunosorbent assay (ELISA) can be used to detect APCA. METHODOLOGY: Study subjects were 134 patients (74 men, 60 women; mean age, 63 years; range, 18-88 years) with gastric carcinoma, gastric ulcer, duodenal ulcer, gastritis, type A gastritis or pernicious anemia and H. pylori-negative normal mucosa subjects in the stomach. APCA was measured in all subjects by our ELISA method. Results of ELISA were compared with results of indirect immunofluorescence (IIF). RESULTS: The percentage of samples that were APCA-positives by IIF at a 1/20 or greater serum dilutions was similar to that by ELISA (86.9%). Agreement between ELISA and IIF for presence of APCA was 78.3% in patients with gastric carcinoma, 80.1% (gastric ulcer), 59.1% (duodenal ulcer), 51.7% (gastritis), 75.0% (type A gastritis), 100% (pernicious anemia) and 80.0% (normal). CONCLUSIONS: ELISA is a useful method for detection of APCA for diagnosis of PA and type A gastritis.

Adolescent↗