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M Yoshihara

Publications and source records attributed to M Yoshihara.

At least 19 recordsLinked to original sources
PubMed2006

Novel heteroduplex method using small cytology specimens with a remarkably high success rate for analysing EGFR gene mutations with a significant correlation to gefitinib efficacy in non-small-cell lung cancer.

We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.

Adult↗
PubMed2006

Endoscopic submucosal dissection for residual/local recurrence of early gastric cancer after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) is a widely accepted treatment for early gastric cancer; however, incomplete resection with residual local disease and recurrences continues to be a difficult problem. The aim of this study was to evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for residual/local recurrent early gastric cancer lesions after EMR. PATIENTS AND METHODS: The en bloc resection rate, histologically complete resection rate, complications, and local recurrence were assessed in 15 patients who underwent ESD for residual/local recurrent early gastric cancer lesions after EMR. RESULTS: The nonlifting sign after injection of a glycerin solution was positive due to scar formation in all cases. En bloc resection was attempted in all cases, with a complete resection rate of 93.3 % (14 of 15). The lesion was completely resected with histologically adequate margins in the 14 patients who received complete en bloc resection. The average operation time was 85.4 +/- 52.9 min, and the mean follow-up period for all patients was 18.1 +/- 7.4 months. Major bleeding during the procedure in one case was the only complication (one of 15, 6.7 %). None of the patients experienced recurrence of early gastric cancer after ESD. CONCLUSIONS: ESD appears to be a safe and effective treatment for residual/local recurrent early gastric cancer lesions after EMR, and it is useful for histological confirmation of successful treatment.

Aged↗
PubMed2006

Nuclear and mitochondrial DNA microsatellite instability in gastrointestinal stromal tumors.

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Nuclear (nMSI) and mitochondrial microsatellite instability (mtMSI) play important roles in tumorigenesis in various organs. The aim of this study was to evaluate the role of nMSI and mtMSI in GISTs. METHODS: Samples from 74 mesenchymal tumors were collected. nMSI and mtMSI were examined by microsatellite assay at BAT26 and D310 mononucleotide repeats in mtDNA, respectively. We compared nMSI, mtMSI and clinicopathologic features, including patient age and sex, tumor location, tumor size, presence of tumor ulceration and presence of distant metastasis, for 51 GISTs for which these data were available. RESULTS: nMSI and mtMSI were detected in 3 (5%) and 10 (16%) of the 62 GISTs, respectively. There was no significant relationship between nMSI, mtMSI and clinicopathologic features. CONCLUSION: These results suggest that mtMSI may play a role, but that nMSI may play little role in the development of GISTs.

Adult↗
PubMed2005

Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up.

BACKGROUND: It is controversial as to whether the development of gastric cancer is influenced by Helicobacter pylori eradication. If eradication itself influences the tumour morphology, this may affect the tumour discovery rate. AIM: To investigate the morphological changes in the gastric neoplasm after H. pylori eradication. METHODS: We studied 37 patients with eradication therapy. After a 1-month follow-up, endoscopic re-evaluation was performed and the appearance was compared with first image. All lesions were resected endoscopically, and were subjected to histological assessment and to immunohistochemistry. Serum gastrin levels were determined before and after eradication. RESULTS: Twenty-nine of 37 patients underwent successful eradication. The appearance of 11 lesions (33% of 33 lesions) became indistinct after successful eradication. All lesions were of the superficial-elevated type and the height of the lesions decreased. We detected normal columnar epithelium over the neoplasm in eight of the lesions. Higher expression of single-stranded deoxyribonucleic acid in the deep area was characteristic in tumours with an indistinct appearance. These changes did not correlate with the serum gastrin levels. CONCLUSIONS: The morphology of the gastric neoplasm change after eradication in the short-term. This may contribute to the decreased tumour discovery rate.

Adenocarcinoma↗
PubMed2005

Loss of heterozygosity on chromosome 10p14-p15 in colorectal carcinoma.

High frequencies of loss of heterozygosity (LOH) on chromosome 10p14-p15 have been reported in various tumors, including gliomas, pulmonary carcinoid tumors and cervical, hepatic, prostatic and esophageal carcinomas. However, LOH on chromosome 10p14-p15 in colorectal tumors has not been reported. Therefore, we examined LOH on chromosome 10p14-p15 in 60 colorectal carcinomas (21 superficial and 39 advanced types) by microsatellite assay. Three microsatellite loci, D10S191 (10p14), D10S558 and D10S249 (10p15) were examined by polymerase chain reaction [early colorectal carcinomas, LOH of markers D10S191 (36%), D10S558 (7%) and D10S249 (11%), and in advanced colorectal carcinomas, LOH of markers D10S191 (20%), D10S558 (13%) and D10S249 (33%)]. There were no significant associations between LOH on chromosome 10p14-p15 and clinicopathologic features, including patient age, sex, tumor location, depth of invasion, histologic type, lymph node metastasis and prognosis. These data suggest that a putative tumor suppressor gene associated with colorectal carcinogenesis may be located on chromosome 10p14-p15 and that alteration of this gene may be involved in the development but not progression of colorectal tumors.

Aged↗
PubMed2004

Magnifying gastroendoscopy for diagnosis of histologic gastritis in the gastric antrum.

BACKGROUND: We investigated the potential of magnifying endoscopy for diagnosis of histologic gastritis in the gastric antrum. In addition, we investigated whether magnifying endoscopy can be applied for evaluation of Helicobacter pylori eradication therapy. METHODS: We examined 176 Japanese patients including 53 with H. pylori eradication. We evaluated the antrum by magnifying observation and ordinary endoscopic findings, and compared these results. Biopsy specimens were taken from the sites observed. RESULTS: The magnified views were classified into four types. Histology of the biopsy specimens allowed us to match the four magnified views with normal mucosa with fundic glands, normal mucosa with pyloric glands, mucosa with gastritis and intestinal metaplasia/epithelial hyperplasia. The types of magnifying appearances were specific enough for the diagnosis of histologic gastritis (148 out of the 176 (82.4%) cases; sensitivity, 96.3%; specificity, 73.7%). We could accurately diagnose the histologic gastritis by magnifying endoscopy in 49 out of the 53 (92%) cases with H. pylori eradication, while only in 38% by ordinary endoscopy. The accuracy of diagnosis was statistically higher with the use of magnifying endoscopy than with ordinary endoscope (P < 0.001). CONCLUSION: Magnifying gastroendoscopy is useful to judge the histologic gastritis, especially, in cases with H. pylori eradication.

Adult↗
PubMed2004

Characteristics and trends of clarithromycin-resistant Helicobacter pylori isolates in Japan over a decade.

Clarithromycin has been administered to patients in Japan since 1991. Clarithromycin-resistant Helicobacter pylori strains have been on the rise in Japan. We obtained H. pylori isolates between 1989 and 2000 and examined mutations of the 23S rRNA gene, which are closely associated with clarithromycin resistance. Isolates were obtained from 356 patients with H. pylori infection treated at the Hiroshima University. Sixty-one of the patients received clarithromycin-based H. pylori eradication therapy. Mutations of the 23S rRNA gene were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by sequencing analysis. Mutant strains were found in 42 of the 356 patients (11.8%). The prevalence of mutant strains increased from 0 to 20.4% during the 12-year study period. The prevalence increased to more than 10% by 1995 and then to more 20% after 1999. The H. pylori eradication rate was significantly higher in patients with wild-type strains than in patients with mutant strains (72.0 vs. 36.4%, p = 0.024). Our data indicate that clarithromycin-resistant H. pylori strains have increased rapidly since 1995 and that the effectiveness of clarithromycin-based H. pylori eradication therapies may soon be compromised. Other new therapies may be necessary as first-line treatments in Japan.

Adolescent↗
PubMed2003

The long-term effect of Helicobacter pylori eradication therapy on symptoms in dyspeptic patients with fundic atrophic gastritis.

AIM: To investigate whether curing Helicobacter pylori infection improves symptoms over the long-term in Japanese patients with nonulcer dyspepsia and fundic atrophic gastritis. METHODS: Ninety H. pylori-positive dyspeptic patients with fundic atrophic gastritis were enrolled in this study. We performed a randomized double-blind placebo-controlled trial comparing triple therapy (n=45) with that of placebo alone (n=45). Inflammation and mucosal atrophy were scored according to the Updated Sydney System. Symptoms were scored on a scale of 0 to 3 for six items. Fasting samples of gastric juice were taken before endoscopy, and gastric pH was determined. Serum gastrin and pepsinogen levels were measured, and body mass index was determined. These patients were followed up for 3 years, and all measures were evaluated both before and after therapy. RESULTS: Significant improvement in dyspeptic symptoms and gastritis scores, significant decrease in gastric pH, and significant increase in body mass index were found after 3 years eradication in nonulcer dyspepsia patients treated successfully for H. pylori infection. There were no significant changes in the placebo group. CONCLUSION: Our study shows that eradicating of H. pylori results in significant long-term reduction in symptoms of nonulcer dyspepsia with fundic atrophic gastritis.

Adult↗
PubMed2003

Long-term observation of reflux oesophagitis developing after Helicobacter pylori eradication therapy.

BACKGROUND: Development of reflux oesophagitis after Helicobacter pylori eradication therapy has been reported, but the prognosis is not well known. AIM: To evaluate the prognosis of patients with reflux oesophagitis that developed after eradication therapy by long-term observation. METHODS: Forty-five patients who developed reflux oesophagitis after successful H. pylori eradication therapy were followed up prospectively. All 45 patients were followed up by endoscopy more than 3 years after onset of reflux oesophagitis (3-year follow-up group) and nine were followed up more than 5 years after onset (5-year follow-up group). Endoscopic observations were performed yearly or when upper gastrointestinal symptoms recurred. Reflux oesophagitis was graded according to the Los Angeles Classification System. Presence of gastro-oesophageal reflux symptoms and medication of proton pump inhibitors, H2-blockers or prokinetics were investigated at final endoscopy. RESULTS: All patients were classified as grade A or B at initial endoscopy. At final observation, the grade of reflux oesophagitis improved in 35/45 (78.8%) patients from the 3-year follow-up group and 7/9 (78.8%) patients from the 5-year follow-up group. Reflux oesophagitis progressed from grade A to B in only four (8.9%) patients from the 3-year follow-up group and in no patients in the 5-year follow-up group. No patient progressed to grade C or D. Gastro-oesophageal reflux symptoms were seen in 12 patients (26.7%) from the 3-year follow-up group and four patients (44.4%) from the 5-year follow-up group. Among them, medication was needed continuously in only six (13.3%) and two (22.2%) patients, respectively. CONCLUSIONS: Reflux oesophagitis, which develops after H. pylori eradication therapy, rarely becomes a long-term clinical problem among patients who complete therapy successfully.

Amoxicillin↗
PubMed2003

The specific expression of hypoxia inducible factor-1alpha in human gastric mucosa induced by nonsteroidal anti-inflammatory drugs.

BACKGROUND: Hypoxia is a cause of gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The expression of hypoxia inducible factor-1alpha (HIF-1alpha) reflects the status of tissue ischaemia. AIM: To investigate the effect of NSAID administration on the expression of HIF-1alpha in human gastric mucosa. METHODS: We employed 71 patients including 14 with NSAID administration. The HIF-1alpha expression was estimated by immunohistochemistry using monoclonal antibody (H1alpha67) and raised antiserum (HI-3). Vascular endothelial growth factor expression was also examined by immunohistochemistry. HI-3 recognized hypoxia-induced protein in HeLa cells. RESULTS: In human gastric mucosa, HIF-1alpha was mainly expressed in the nuclei of the surface epithelial cells and in the neck zone both by use of HI-3 and of H1alpha67. The expression of vascular endothelial growth factor correlated well with that of HIF-1alpha. The level of HIF-1alpha in the surface epithelium was significantly higher in patients with administration of NSAIDs than those without NSAID use (P < 0.001) both in the gastric corpus and antrum. Helicobacter pylori infection did not affected the levels of HIF-1alpha. Long-term administration of rebamipide reduced the level of HIF-1alpha. CONCLUSION: HIF-1alpha expression is a new biological marker of ischaemia especially in NSAID-related gastric lesions.

Adolescent↗
PubMed2003

Helicobacter pylori infection influences tumor growth of human gastric carcinomas.

BACKGROUND: Helicobacter pylori infection is considered a risk factor for gastric carcinoma. However, the effect of eradication therapy in gastric carcinoma patients is not well known. The aim of this study was to investigate the relationship between H. pylori infection and tumor growth of gastric carcinoma. METHODS: Fifty-one patients with gastric carcinoma participated in the study. Thirty-three were H. pylori-positive, 6 were H. pylori-negative, and 12 were diagnosed with gastric carcinoma after eradication of H. pylori. To investigate tumor growth of gastric carcinoma, cell proliferation and angiogenesis of the tumors were evaluated by immunohistochemical techniques using Ki-67 and CD34. RESULTS: The Ki-67 labeling index was 47.9 +/- 2.6 (mean +/- s) in the H. pylori-positive group, 38.1 +/- 3.6 in the H. pylori-eradicated group, and 22.2 +/- 5.5 in the H. pylori-negative group. It was significantly lower in the H. pylori-eradicated and H. pylori-negative groups than in the H. pylori-positive one, and a significant difference was also found between the H. pylori-positive and H. pylori-eradicated groups. The microvessel counts were 62.5 +/- 3.0, 50.2 +/- 4.0, and 66.0 +/- 9.8 in the positive, eradicated, and negative groups, respectively. A significant difference was found between the H. pylori-positive and H. pylori-eradicated groups. CONCLUSION: Our results suggest that H. pylori infection is associated with cell proliferation, and its eradication may influence tumor vascularity of gastric carcinoma. Therefore, H. pylori eradication therapy may contribute to the suppression of tumor growth.

Aged↗
PubMed2003

Necessity of multiple gastric biopsies from different sites for detection of clarithromycin-resistant Helicobacter pylori strains.

BACKGROUND: It has been reported that approximately 10% of patients infected with Helicobacter pylori have both clarithromycin-susceptible and clathromycin-resistant strains. However, there have been no reports indicating whether only one gastric biopsy is sufficient to detect clarithromycin-resistant strains. METHODS: Sixty-five H. pylori-infected patients were selected for this study, and 40 of them were given clarithromycin-based eradication therapy. Four gastric biopsies, 2 from the antrum and 2 from the corpus, were obtained from each of the 65 patients. Susceptibility of H. pylori strains to clarithromycin was examined by detecting mutations of the 23S ribosomal RNA (rRNA) gene of H. pylori. RESULTS: The clarithromycin-resistant strains were detected in 16 of the 65 (25%) patients. Only 5 of the 16 (31%) patients had the resistant strains in both the antrum and corpus. When only 1 or the other biopsy from the antrum was used, the resistant strains were detected in 8 (50%) or 9 (56%) of the 16 patients. CONCLUSIONS: These data indicate that multiple gastric biopsies from both the antrum and the corpus should be used to detect clarithromycin-resistant H. pylori strains.

Adult↗
PubMed2002

Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa.

We examined the relationship between vascular endothelial growth factor (VEGF)-C expression and lymph node metastases in gastric carcinomas invading the submucosa. Of the six human gastric carcinoma cell lines, two constitutively expressed VEGF-C mRNA. In three of 12 gastric biopsy specimens (25%), VEGF-C mRNA was detected in tumour tissues, but not in corresponding normal mucosa by reverse transcriptase-polymerase chain reaction (RT-PCR). Of the 139 resected gastric carcinomas, 44 (32%) showed intense cytoplasmic VEGF-C immunoreactivity in many cancer cells at the invading edge. VEGF-C immunoreactivity was associated with greater depth of tumour invasion, lymphatic invasion and lymph node metastases. In addition, vessel count was also significantly higher in the VEGF-C immunoreactive tumours than in other tumours. These results suggest that VEGF-C may be involved in the progression of human gastric carcinoma, particularly via lymphangiogenesis. VEGF-C expression at the invading edge of a gastric carcinoma may be a sensitive marker for metastasis to the lymph nodes.

Blotting, Northern↗
PubMed2002

Long-term rebamipide therapy improves Helicobacter pylori-associated chronic gastritis.

We investigated an antiinflammatory effect of rebamipide [2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid], a gastroprotective agent, in H. pylori-associated gastritis. Eighty-six patients with H. pylori-positive chronic gastritis were enrolled: 53 were treated with rebamipide (300 mg daily for 12 months) and 33 served as controls. Significant decreases in mononuclear cell infiltration into the antrum and corpus were noted in the rebamipide treatment group (before vs after, 1.42 +/- 0.15 vs 1.02 +/- 0.15; P < 0.01 and 1.60 +/- 0.15 vs 1.21 +/- 0.14; P < 0.05, respectively). Levels of infiltrating neutrophil were also decreased in the antrum (before vs after, 0.98 +/- 0.14 vs 0.70 +/- 0.13; P < 0.05) and were associated with a decrease in iNOS production. Sera from patients treated with rebamipide showed a significant decrease in gastrin (276.3 +/- 58.3 pg/ml vs 173.0 +/- 34.2 pg/ml; P < 0.05), whereas no change was observed in the control group. These suggest that long-term rebamipide treatment improved histologic gastritis and decreased serum gastrin levels in H. pylori-associated gastritis.

Alanine↗
PubMed2002

Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis.

AIM: : To investigate the effect of the eradication of Helicobacter pylori on histological gastritis. METHODS: : Twenty-six patients with moderate to severe atrophy received successful eradication therapy of H.pylori. Four patients dropped out and 22 were followed up prospectively for 5 years. The grades of gastritis were estimated from gastric biopsy specimens. The grade of intestinal metaplasia was also evaluated by dye-endoscopy using methylene blue (methylthioninium chloride). The serum levels of pepsinogen, gastrin and anti-parietal cell antibody were also determined. RESULTS: : The grades of atrophy decreased in patients with successful eradication therapy in the gastric corpus (before vs. 5 years after eradication, 2.09 +/- 0.15 vs. 0.91 +/- 0.17; P < 0.01) and in the antrum (2.14 +/- 0.17 vs. 1.36 +/- 0.17; P < 0.01). The levels of intestinal metaplasia were also decreased in the corpus (0.91 +/- 0.24 vs. 0.50 +/- 0.16; P < 0.05) and in the antrum (1.41 +/- 0.20 vs. 1.00 +/- 0.16; P < 0.05), which was also demonstrated by the methylene blue (methylthioninium chloride) staining method (33.4 +/- 8.2% vs. 23.0 +/- 6.5%; P < 0.05). The improvement of corpus atrophy correlated well with the high serum level of pepsinogen I (P = 0.005), but showed no correlation with the levels of anti-parietal cell antibody. CONCLUSIONS: : These results suggest that gastric atrophy and intestinal metaplasia are reversible events in some patients.

Adult↗
PubMed2002

Role of anti-parietal cell antibody in Helicobacter pylori-associated atrophic gastritis: evaluation in a country of high prevalence of atrophic gastritis.

BACKGROUND: Helicobacter pylori plays an important part in the progression of atrophic gastritis; however, markers for predicting the progression of atrophic gastritis remain unidentified. We investigated the relation between the degree of atrophic gastritis and the amount of anti-parietal cell antibodies (APCAs) present. METHODS: In 219 Japanese patients, APCA was investigated by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. The grade of corpus atrophy was estimated by histology and serum pepsinogen levels. Serum levels of pepsinogen were evaluated by radioimmunoassay. RESULTS: Helicobacter pylori infection did not affect the APCA levels determined by ELISA. Long-term administration of proton-pump inhibitors and H. pylori eradication did not influence the levels of APCAs. However, in H. pylori-positive patients, the levels of APCA determined by ELISA were statistically higher in patients with severe atrophy than in those with mild atrophy as determined histologically (0.67+/-0.48 versus 0.45+/-0.40; A492, mean+/-s, P=0.01) and serologically by pepsinogen levels (0.66+/-0.51 versus 0.44+/-0.40. P=0.002). The levels of pepsinogen I/II ratio were correlated with APCA levels only in the H. pylori-positive group. Western blotting showed that major antigen was identical with the beta-subunit of H+,K+-ATPase. CONCLUSION: APCA plays an important part in the progression of corpus atrophy after H. pylori infection.

Adolescent↗
PubMed2002

Human telomerase reverse transcriptase, p53 and Ki-67 expression and apoptosis in colorectal serrated adenoma.

BACKGROUND: Serrated adenoma (SA) has recently been proposed as a distinct histological lesion of the colorectum. However, no definite histopathologic criteria for SA have been established, and its histogenesis and natural history remain unclear. METHODS: We analysed 25 hyperplastic polyps (HPs), 26 low-grade SAs (LG-SAs), 32 high-grade SAs (HG-SAs), 18 low-grade tubular adenomas (LG-TAs), 16 high-grade TAs (HG-TAs) and 20 carcinoma in situ (CIS). To clarify molecular features of SA, we used in situ hybridization to examine the expression of human telomerase reverse transcriptase (hTERT), immunohistochemistry to examine the expressions of p53 and Ki-67, and in situ DNA nick end labeling to detect apoptotic cells. RESULTS: The incidence of hTERT expression was 1 (4.0%) of 25 for HP, 12 (46.2%) of 26 for LG-SA, 18 (56.3%) of 32 for HG-SA, 6 (33.3%) of 18 for LG-TA, 7 (43.8%) of 16 for HG-TA, 12 (80.0%) of 15 for CIS, respectively. The incidence of hTERT expression in SA was significantly higher than that in HP. Seventeen (29%) of the 58 SAs were regarded as positive for p53 protein, but none of the HPs showed p53 immunoreactivity. Ki-67 labeling index in SA, TA and CIS was significantly higher than that in HP. The apoptototic index was not significantly different between HP, SA, TA and CIS. In HG-SA, the incidence of hTERT expression in p53-positive lesions was significantly higher than that in p53-negative lesions. CONCLUSIONS: These results suggest that hTERT and p53 expression increase in the early stages of carcinogenesis in SA and that SA has a malignant transformation similar to that of TA. It may be useful to investigate hTERT and p53 expression for differential diagnosis of SA from HP.

Adenoma↗