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Biomedical subjects

Manabu Muto

Publications and source records attributed to Manabu Muto.

28 records · Page 2Linked to original sources
PubMed2003

Esophageal stenosis after endoscopic mucosal resection of superficial esophageal lesions.

BACKGROUND: Although bleeding and perforation are generally recognized major complications of endoscopic mucosal resection, esophageal stricture after endoscopic mucosal resection has not been well studied. Factors associated with the occurrence and severity of esophageal stenosis after endoscopic mucosal resection were investigated. METHODS: Two hundred sixteen superficial esophageal lesions in 137 consecutive patients who underwent endoscopic mucosal resection from February 1993 through March 2001 were retrospectively studied. The circumferential extent of the mucosal defect after endoscopic mucosal resection was classified into 4 groups: under one fourth, one fourth to one half, one half to three fourths, and over three fourths. The longitudinal length of the mucosal defect was also evaluated. Stenosis was diagnosed when a standard endoscope (11-mm diameter) could not be passed through the stricture. RESULTS: Esophageal stenosis developed after endoscopic mucosal resection of 13 lesions (6.0%). In all these cases endoscopic mucosal resection resulted in a mucosal defect that involved over three fourths of the luminal circumference. In the subgroup of patients with mucosal defects involving over three fourths of the circumference, those with a mucosal defect over 30 mm long required more frequent balloon dilatation (mean 8 [4.3] times) and the stenosis was of longer duration (mean 16 [17.7] months) than those with defects 30 mm or less in length (respectively, 1 [0.6] times and 2 [1.9] months). CONCLUSIONS: A circumferential mucosal defect involving over three fourths the circumference of the esophagus after endoscopic mucosal resection was significantly associated with the subsequent development of esophageal stenosis. In addition, mucosal defects longer than 30 mm were associated with greater severity of stenosis. When endoscopic mucosal resection is performed for superficial esophageal lesions, removal of excess mucosa should be avoided.

Age Distribution↗
PubMed2003

[Controversies in the treatment of esophageal cancer from the viewpoint of medical oncology].

Recent advances in non-surgical treatments such as endoscopic mucosal resection (EMR) and chemoradiotherapy (CRT) have provided various advantages with clinically meaningful impacts in the treatment of esophageal cancer. EMR is a standard treatment for mucosal cancer and is being investigated for use in combination with CRT for submucosal cancer. Definitive CRT has also reported to results in survival mostly comparable with surgery in the loco-regional stage. A randomized trial comparing surgery alone with definitive CRT in stage I disease is also planned. In patients with T4 disease, it appears that CRT is becoming a standard. However, various issues and limitations remain with non-surgical treatments. To improve treatment results, closer collaboration between surgeons and radiation oncologists is necessary.

Chemotherapy, Adjuvant↗
PubMed2003

Alcohol flushing, alcohol and aldehyde dehydrogenase genotypes, and risk for esophageal squamous cell carcinoma in Japanese men.

Alcohol flushing after light drinking is triggered mainly by severe acetaldehydemia in individuals possessing inactive aldehyde dehydrogenase (ALDH)-2. Inactive ALDH2 encoded by ALDH2*1/2*2 and the low-activity form of alcohol dehydrogenase (ADH)-2 encoded by ADH2*1/2*1 enhance the risk for esophageal cancer in Japanese light to heavy drinkers, a significant association that emphasizes the importance of screening tests for inactive ALDH2 based on alcohol flushing. The objectives of the present report were (a). to evaluate the reliability of a simple questionnaire that asks about both current and past flushing for detecting inactive ALDH2 and (b). to predict cancer risk based on flushing in a case-control manner. The study subjects consisted of 233 Japanese men with esophageal squamous cell carcinoma and 610 cancer-free Japanese men. When current or former flushing individuals were considered to have inactive ALDH2, the sensitivity and specificity of the test were 84.8% and 82.3%, respectively, for the cases and 90.1% and 88.0%, respectively, for the controls. To clarify the characteristics of men who had genetically inactive ALDH2 but did not report alcohol flushing, we analyzed individuals possessing the ALDH2*1/2*2 genotype and found that those who also had ADH2*1/2*1 (both cases and controls) tended not to report current flushing, and those who did not report current flushing (controls only) tended to be heavier drinkers. As compared with overall never or rare drinking, the cancer risks for light (1-8.9 units/week; 1 unit = 22 g of ethanol), moderate (9-17.9 units/week), and heavy (18+ units/week) drinkers with current or former flushing (odds ratio = 6.69, 42.66, and 72.86, respectively) significantly exceeded the risks for those who had never flushed (odds ratio = 1.27, 10.12, and 15.61, respectively), even after adjustment for age, smoking, and diet. The flushing questionnaire may be used in large-scale epidemiological studies as a surrogate marker of ALDH2 genotype to predict individual cancer risk.

Adult↗
PubMed2002

A new technique for endoscopic mucosal resection with an insulated-tip electrosurgical knife improves the completeness of resection of intramucosal gastric neoplasms.

BACKGROUND: En bloc resection is optimal for the cure of gastric neoplasms by endoscopic mucosal resection (EMR). A new technique was developed for EMR by using an insulated-tip electrosurgical knife (IT-EMR). This is a report on the clinical application of IT-EMR. METHODS: IT-EMR of 123 gastric tumors was performed in 120 patients. The en bloc resection rate, completeness of resection, and associated complications were evaluated. The local recurrence rate was studied for 90 intramucosal lesions followed for more than 6 months without further treatment. RESULTS: The en bloc resection rate for all lesions was 54% (67/123 lesions). The en bloc resection rates were 82% (27/33) for lesions 10 mm or less in size, 54% (29/54) for those between 11 mm and 20 mm, and 31% (11/36) for those of over 20 mm. Complete resection rates in the cases with en bloc resection were 78% (21/27) for lesions 10 mm or less in size, 76% (22/29) for those between 11 mm and 20 mm, and 73% (8/11) for those over 20 mm. There were no episodes of major bleeding that required blood transfusion or surgical intervention; minor bleeding including oozing occurred in 38% (47/123). Perforation occurred in 1 case (1/123; 0.8%). The local recurrence rate for lesions resected en bloc was significantly lower than that for lesions resected as multiple fragments (respectively, 2/49; 4.1% vs. 7/41; 17%: p = 0.041). CONCLUSIONS: IT-EMR is feasible in clinical practice and has a high en bloc resection rate. En bloc resection may reduce the rate of local recurrence.

Adenoma↗
PubMed2002

Association of multiple Lugol-voiding lesions with synchronous and metachronous esophageal squamous cell carcinoma in patients with head and neck cancer.

BACKGROUND: Patients with squamous cell carcinoma of the head and neck have a high prevalence of second primary esophageal squamous cell carcinomas. This study assessed the risk of developing second primary esophageal squamous cell carcinomas in patients with squamous cell carcinoma of the head and neck based on multiplicity of Lugol-voiding lesions observed by chromoendoscopy and patient characteristics. METHODS: Three hundred eighty-nine patients with newly diagnosed squamous cell carcinoma of the head and neck were divided into 4 groups: no Lugol-voiding lesions; several (</=10) small Lugol-voiding lesions; many (>10) small Lugol-voiding lesions; and many irregularly shaped, multiform Lugol-voiding lesions. Relative risk for the development of synchronous second primary esophageal squamous cell carcinomas was investigated by using univariate and multivariate analysis. Metachronous second primary esophageal squamous cell carcinomas was also studied among 227 patients followed more than 1 year after initial examination. RESULTS: Fifty-four (14%) of the 389 patients were found to have synchronous second primary esophageal squamous cell carcinomas. In particular, 55% of the patients with many irregular-shaped multiform Lugol-voiding lesions had synchronous second primary esophageal squamous cell carcinomas. Univariate analysis showed that the presence of many irregular-shaped multiform Lugol-voiding lesions, drinking habit, male gender, and smoking were significant risk factors for the development of synchronous second primary esophageal squamous cell carcinomas. Multivariate analysis also revealed that many irregular-shaped multiform Lugol-voiding lesions (odds ratio: 21.4; p < 0.001) and drinking habit (odds ratio: 3.3; p < 0.02) were independent risk factors. During follow-up, 7 patients (3%) had metachronous second primary esophageal squamous cell carcinomas; 6 had many irregular-shaped multiform Lugol-voiding lesions and the seventh had many small Lugol-voiding lesions in the background mucosa. CONCLUSIONS: The presence of numerous irregular-shaped multiform Lugol-voiding lesions was closely associated with second primary esophageal squamous cell carcinomas in patients with squamous cell carcinoma of the head and neck. This might be explained by the concept of "field cancerization." Ingestion of alcohol may play an important role in the occurrence of this phenomenon.

Adult↗
PubMed2002

Association between aldehyde dehydrogenase gene polymorphisms and the phenomenon of field cancerization in patients with head and neck cancer.

Patients with squamous-cell carcinoma in the head and neck (HNSCC) often develop second primary esophageal squamous-cell carcinomas (ESCC). In addition, widespread epithelial oncogenic alterations are also frequently observed in the esophagus and can be made visible as multiple Lugol-voiding lesions (multiple LVL) by Lugol chromoendoscopy. Multiple occurrences of neoplastic change in the upper aerodigestive tract have been explained by the concept of 'field cancerization', usually associated with repeated exposure to carcinogens such as alcohol and cigarette smoke. However, the etiology of second ESCC in HNSCC patients remains unclear and acetaldehyde, the first metabolite of ethanol, has been implicated as the ultimate carcinogen in alcohol-related carcinogenesis. We first investigated the relation between second ESCC and multiple LVL in 78 HNSCC patients. Multiple LVL and second ESCC were observed in 29 (37%) and 21 (27%) patients, respectively. All of the second ESCC were accompanied by multiple LVL. This may indicate that episodes of multiple LVL are precursors for second ESCC. We then examined the association of multiple LVL with the patients' characteristics, including genetic polymorphisms of the alcohol metabolizing enzymes, alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2). We also investigated acetaldehyde concentrations in the breath of 52 of the 78 patients. All the patients with multiple LVL were both drinkers and smokers. Multivariable logistic analysis showed that the inactive ALDH2 allele (ALDH2-2) was the strongest contributing factor for the development of multiple LVL (odds ratio 17.6; 95% confidence intervals 4.7-65.3). After alcohol ingestion, acetaldehyde in the breath was elevated to a significantly higher level in all patients with the ALDH2-2 allele than in those without it. The high levels of breath acetaldehyde were significantly modified by the slow-metabolizing ADH3-2 allele. These results reveal strong evidence for a gene-environmental interaction between the ALDH2-2 allele and alcohol consumption, for the risk of developing multiple LVL, resulting in the development of second ESCC in patients with HNSCC. Ultimately, increased local acetaldehyde exposure thus appears to be a critical determinant of the phenomenon of 'field cancerization'.

Alcohol Drinking↗
PubMed2002

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione S-transferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma.

The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-2 (ADH2), ADH3, and glutathione S-transferase M1 (GSTM1) influence the metabolism of alcohol and other carcinogens. The ALDH2*1/2*2 genotype, which encodes inactive ALDH2, and ADH2*1/2*1, which encodes the low-activity form of ADH2, enhance the risk for esophageal cancer in East Asian alcoholics. This case-control study of whether the enzyme-related vulnerability for esophageal cancer can be extended to a general population involved 234 Japanese men with esophageal squamous cell carcinoma and 634 cancer-free Japanese men who received annual health checkups. The GSTM1 genotype was not associated with the risk for this cancer. Light drinkers (1-8.9 units/week) with ALDH2*1/2*2 had an esophageal cancer risk 5.82 times that of light drinkers with ALDH2*1/2*1 (reference category), and their risk was similar to that of moderate drinkers (9-17.9 units/week) with ALDH2*1/2*1 (odds ratio = 5.58). The risk for moderate drinkers with ALDH2*1/2*2 (OR = 55.84) exceeded that for heavy drinkers (18+ units/week) with ALDH2*1/2*1 (OR = 10.38). Similar increased risks were observed for those with ADH2*1/2*1. A multiple logistic model including ALDH2, ADH2, and ADH3 genotypes showed that the ADH3 genotype does not significantly affect the risk for esophageal cancer. For individuals with both ALDH2*1/2*2 and ADH2*1/2*1, the risk of esophageal cancer was enhanced in a multiplicative fashion (OR = 30.12), whereas for those with either ALDH2*1/2*2 or ADH2*1/2*1 alone the ORs were 7.36 and 4.11. In comparison with the estimated population-attributable risks for preference for strong alcoholic beverages (30.7%), smoking (53.6%) and for lower intake of green and yellow vegetables (25.7%) and fruit (37.6%), an extraordinarily high proportion of the excessive risk for esophageal cancer in the Japanese males can be attributed to drinking (90.9%), particularly drinking by persons with inactive heterozygous ALDH2 (68.5%). Education regarding these risky conditions in connection with ALDH2 and ADH2 is vitally important in a new strategic approach aimed at preventing esophageal cancer in East Asians.

Adult↗
PubMed2002

Three novel single nucleotide polymorphisms in UGT1A10.

Three novel single nucleotide polymorphisms (SNPs) were found in the UDP-glucuronosyltransferase (UGT) 1A10 gene from 24 Japanese patients with various cancers who were administered the anti-tumor drug, irinotecan (CPT-11). The detected SNPs were as follows: 1) SNP, MPJ6_U1A003; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CAGATGCCATGAC/TTTTCAAGGAGAG-3'. 2) SNP, MPJ6_U1A004; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CCTAGAAATAGCC/TTCTGAAATTCTC-3'. 3) SNP, MPJ6_U1A030; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-GGTTGTAGTCATG/ACCAGAGGTGAGT-3' All the three SNPs were located in exon 1 and their frequencies were all 0.021. Among these SNPs, MPJ6_U1A003 and U1A030 resulted in amino acid alterations, T202I and M59I, respectively. The third SNP, MPJ6_U1A004, introduced a synonymous amino acid change (A231A).

Journal Article↗
PubMed2000

Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with bone metastasis.

BACKGROUND: Patients with bone metastasis of gastric cancer occasionally experience disseminated intravascular coagulation (DIC), with a very poor prognosis.METHODS: We treated 18 gastric cancer patients with bone metastasis with sequential methotrexate and 5-fluorouracil (sequential MTX/5-FU therapy). The treatment schedule comprised weekly administration of methotrexate (MTX; 100 mg/m(2), i.v. bolus) followed by 5-fluorouracil (5-FU; 600 mg/m(2), i.v. bolus) after an interval of 3 h. Calcium leucovorin (10 mg/m(2), p.o. or i.v.) was administered six times, every 6 h starting 24 h after the administration of MTX.RESULTS: In 11 patients with measurable metastatic lesions, the response rate was 64% (7/11). Nine patients (50%) had DIC before the initiation of chemotherapy, and 8 of them (89%) recovered from it. Two of these 9 patients (22%) survived for more than 1 year. The median survival times for all patients and for the 9 with DIC were 186 and 113 days, respectively. Grade 4 leukopenia was observed in 3 patients (17%). No treatment-related deaths occurred.CONCLUSION: Sequential MTX/5-FU therapy may have palliative potential and may be a feasible treatment for gastric cancer patients with bone metastasis with or without DIC.

Journal Article↗