Biomedical subjects

Manabu Muto

Publications and source records attributed to Manabu Muto.

At least 19 recordsLinked to original sources

PubMed2007

Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice.

In this study, we evaluated the inhalation toxicity of acetaldehyde in Aldh2 KO (Aldh -/-) mice, using pathological method. Male C57BL/6 (Aldh2 +/+) mice and Aldh -/- mice were exposed to atmospheres containing acetaldehyde at levels of 0, 125, and 500 ppm for 24 h/day during 14 days. Although the average blood acetaldehyde concentration of Aldh -/- mice was higher than that of Aldh2 +/+ mice in the acetaldehyde exposure group, observable effects by the acetaldehyde exposure on the lung and liver were not different between wild type and ALDH2 null mice. In Aldh2 -/- mice, the levels of 1) erosion of respiratory epithelium and the subepithelial hemorrhage in nose, 2) hemorrhage in nasal cavity, 3) degeneration of respiratory epithelium in larynx, pharynx and trachea, and 4) degeneration of dorsal skin were higher compared with Aldh2 +/+ mice, indicating that Aldh2 -/- mice are more acetaldehyde-sensitive than Aldh2 +/+ mice. This is the first example for studying pathological effects of Aldh2 deficiency using Aldh -/- mice exposed to a low level of acetaldehyde.

Acetaldehyde↗

PubMed2006

Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma.

The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-1B (ADH1B, previously called ADH2), and ADH1C (previously called ADH3) affect the metabolism of alcohol. The inactive ALDH2 encoded by ALDH2*1/*2 and the less-active ADH1B encoded by ADH1B*1/*1 increase the risk of esophageal squamous cell carcinoma in East Asian drinkers. This case-control study involved 96 Japanese men with oral and pharyngeal squamous cell carcinoma (hypopharyngeal cancer in 43 patients and oral/oropharyngeal cancer in 53) and 642 cancer-free Japanese men. The risk of the cancers overall and of hypopharyngeal cancer was increased 3.61- and 10.08-fold, respectively, by ALDH2*1/*2 among moderate-to-heavy drinkers (9+ units/week; one unit = 22 g of ethanol), but the risk of oral/oropharyngeal cancer was not significantly affected by the ALDH2 genotype. The results obtained with a simple alcohol flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping. Among moderate-to-heavy drinkers, men with the less-active ADH1B*1/*1 had a significantly higher risk of the cancers overall, of hypopharyngeal cancer, and of oral/oropharyngeal cancer (OR = 5.56, 7.21 and 4.24, respectively). In view of the linkage disequilibrium between ADH1B and ADH1C, the ADH1C genotype does not significantly affect cancer risk. The significant independent risk factors for oral and pharyngeal cancer overall among moderate-to-heavy drinkers were inactive ALDH2*1/*2, less-active ADH1B*1/*1, frequent drinking of strong alcohol beverages straight, smoking, and lower intake of green-yellow vegetables. Educating these risks for cancer of the upper aerodigestive tract could be a useful new strategic approach to the prevention of these cancers in Japanese.

Adult↗

PubMed2006

Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) as first-line therapy for patients with colorectal cancer.

BACKGROUND: Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD. METHODS: The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). RESULTS: A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61% in the 18 patients studied and 64% at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied. CONCLUSIONS: Oxaliplatin (85 mg/m2) with weekly bolus 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.

Adult↗

PubMed2006

Esophageal squamous cell carcinoma and aldehyde dehydrogenase-2 genotypes in Japanese females.

BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) is the key enzyme for elimination of acetaldehyde, an established animal carcinogen produced after drinking. In persons with inactive ALDH2, the body fails to metabolize acetaldehyde rapidly, leading to excessive accumulation of acetaldehyde. Inactive heterozygous ALDH2 enhances the risk of esophageal squamous cell carcinoma (SCC) in Japanese male drinkers. METHODS: We studied whether this is the case for women. The risk factors of esophageal SCC were examined in 52 Japanese women with esophageal SCC and 412 cancer-free Japanese women. RESULTS: The increasing trend in cancer risk according to the quantity of alcohol consumption was significantly steeper in women with inactive heterozygous ALDH2 than in those with active ALDH2 [adjusted odds ratios (ORs) (95% confidence intervals (CIs)) per +7 U/wk increment of alcohol drinking were 3.91 (2.09-7.31) and 1.39 (0.92-2.09), respectively; p = 0.006 for difference in OR; 1 Ut = 22 g of ethanol]. The results obtained using an alcohol-flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping [adjusted ORs (95% CIs) per +7 U/wk increment of alcohol drinking were 3.94 (1.87-8.31) and 1.46 (0.96-2.23) in those with and without flushing, respectively; p = 0.021 for difference in OR]. The risk of esophageal cancer was markedly higher in heavy drinkers with ALDH2*1/*2 than in never/rare drinkers with ALDH2*1/*1 [adjusted OR (95% CI) = 59.1 (4.65-750)]. Other independent significant risk factors of esophageal SCC were smoking, a preference for hot food or drinks, and lower intake of green and yellow vegetables. CONCLUSIONS: Japanese men and women shared several common risk factors of esophageal SCC, including drinking with inactive heterozygous ALDH2.

Adult↗

PubMed2006

Fourteen novel genetic variations and haplotype structures of the TYMS gene encoding human thymidylate synthase (TS).

Forty genetic variations including 14 novel ones were found in the human TYMS gene, which encodes thymidylate synthase, in 263 Japanese cancer patients who received 5-fluorouracil (FU)-based chemotherapy. Three novel variations were located within the 28-bp tandem repeat sequence in the 5'-untranslated region (UTR) and were designated 5Rc, 3Rc-ins and 4Rc. Allele frequencies were 0.021 for 5Rc, 0.006 for 3Rc-ins and 0.002 for 4Rc. Other novel variations included -133G>C and -125G>C in the 5'-UTR; IVS1-278G>A, IVS2-68C>T, IVS2-23T>C, IVS4+122_+123insATTG, IVS4-141G>A, IVS5-100A>T and IVS6-111G>A in the introns; and 1244(*302)A>G and 1264(*322)G>A in the 3'-UTR. The allele frequencies were 0.34 for IVS4+122_+123insATTG, 0.042 for -133G>C, 0.011 for IVS4-141G>A, 0.006 for -125G>C, 0.004 for IVS1-278G>A, IVS2-68C>T, 1244(*302)A>G and 1264(*322)G>A, and 0.002 for IVS2-23T>C, IVS5-100A>T and IVS6-111G>A. Using the detected polymorphisms, linkage disequilibrium (LD) analysis was performed, which divided the TYMS gene into three LD blocks. The 28-bp tandem repeat sequence in the 5'-UTR was assigned as Block 2 with a total of 7 alleles. In Blocks 1 and 3, 7 and 19 haplotypes were determined/inferred, respectively. Our findings provide fundamental and useful information for genotyping TYMS in the Japanese and probably other Asian populations.

3' Untranslated Regions↗

PubMed2006

Expression profiling of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy: clinical implications.

In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy (CRT) has a curative potential even in cases of locally advanced carcinoma. However, only about half of the patients benefit from CRT, and an accurate prediction of sensitivity to CRT is eagerly awaited. Using microarrays, we analyzed gene-expression patterns of pretreatment biopsy specimens from 33 patients with CRT alone including long-term survivors, more than 3 years (14 cases) and short-term survivors, less than 1 year (11 cases). The expression patterns of about 12,600 genes were used to identify genes correlated with survival terms. Fifty-seven genes correlating with short-term survival and 120 genes with long-term survival were identified. The genes involved in the immune response were characteristically upregulated in the long-term survivors, and an immunohistochemical staining confirmed an increased CD8-positive T cell number in the long-term survivors over that in the short-term survivors. In the short-term survivors, on the other hand, increased expression of the genes involved in drug resistance was observed. Our gene list should contribute to the elucidation of the mechanisms of CRT response and contains useful markers for predicting the prognosis of individual ESCC patients treated with CRT alone.

Adult↗

PubMed2006

Array-based comparative genomic hybridization of circulating esophageal tumor cells.

Esophageal squamous cell carcinoma (ESCC) shows a high frequency of lymphatic and/or systemic metastasis, even when the tumor invades only the submucosa. To investigate the genetic alterations in circulating esophageal tumor cells, we performed array-based comparative genomic hybridization (CGH) analysis of 8 DNA samples of xenografts, which were previously established from the thoracic duct lymph of 13 ESCC patients. A total of 5 loci (or genes), 10q21.3 (EGR2), 11q13.3 (CCND1/CyclinD1, FGF4, and EMS1), 11q14 (PAK1), and 22qtel (ARSA) were found to be candidate amplified loci in the xenograft. In contrast, a total of 24 loci including 9p21 (p16 and MTAP) were found to be homozygously deleted candidates in the xenograft. Both p16 homozygous deletion and CCND1 amplification were detected in 6 (75%) and 5 (62.5%) of the 8 xenografts. Furthermore, by quantitative Southern blot analysis, we found p16 homozygous deletion in 30.8% (8/26) of the primary tumors and in 50% (4/8) of the metastasized lymph nodes. The frequency of CCND1 amplification and p16 homozygous deletion is suggested to be associated with ESCC progression. Matrigel invasion assays of p16-deleted ESCC cells showed that restoring wild-type p16 activity into the cells significantly inhibits tumor-cell invasion, suggesting that p16 inactivation could be involved in ESCC invasion. This is the first report showing the genetic alteration of concealed tumor cells in the thoracic duct lymph. The present gene list should be helpful for identifying new amplified and deleted genes in primary ESCCs as well as in metastasized lymph nodes.

Adenoviridae↗

PubMed2005

Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region.

While multiple squamous cell carcinomas are often observed in the esophagus and the head and neck region and confound us about the favorable treatments, the reason why some patients are more likely to develop multiple cancers remains obscure. We statistically analyzed clinical factors in 203 patients with newly diagnosed squamous cell carcinoma, to assess the risk of multiple cancers for the establishment of an effective prevention and screening programs. Widespread epithelial oncogenic alterations were assessed as multiple lugol-voiding lesions (multiple LVL) using lugol chromoendoscopy. Genetic polymorphisms of alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2) were identified by PCR-restriction fragment length polymorphism analysis. Forty patients had synchronous multiple cancers and the remaining 163 had solitary cancer. Presence of multiple LVL was the only independent risk factor for multiple cancers [relative risk (RR) = 67; 95%CI, 15-310]. Multiple LVL was observed in only smoking drinkers. Among them, a multivariate analysis demonstrated that the ALDH2 deficiency allele (RR = 5.7; 95%CI, 2.8-11.6) and the slow metabolizing ADH3 allele (RR = 1.9; 95%CI, 1.1-7.9) were the independent risk factors for multiple LVL. Combination of these alleles lead to increase the risk of multiple LVL. In conclusion, an episode of multiple LVL is a remarkable high risk for multiple cancers both at the esophagus and the head and neck region. The interaction between drinking and the ALDH2 deficiency allele increases the risk. In addition, the slow metabolizing ADH3 allele enhances the risk. Prohibiting the use of alcohol and early detection of cancer are strongly recommended for such individuals.

Alcohol Dehydrogenase↗

PubMed2005

Local recurrence of squamous-cell carcinoma of the esophagus after EMR.

BACKGROUND: Multicentric squamous dysplasia is frequent in the esophagus and can be visualized by chromoendoscopy (Lugol's solution) as multiple Lugol-voiding lesions (LVLs). Although EMR commonly is used to treat superficial esophageal cancer, new lesions can arise and incomplete resection can result in residual disease. Little is known about the risk factors for local recurrence or the appropriate treatment for recurrent lesions. METHODS: A total of 116 consecutive patients with a total of 165 esophageal squamous-cell carcinomas were studied retrospectively. Follow-up examination by means of chromoendoscopy (Lugol's solution) and biopsies was performed every 3 months during the first year after EMR and every 6 months thereafter. Lesions were defined as a local recurrence when cancer was detected at the site of the EMR scar. Risk factors associated with local recurrence were investigated by using logistic analysis. RESULTS: At a median follow-up of 35 months (range 12-110 months), local recurrence was detected for 33 (20%) of 165 lesions. Of the patient-related factors, multivariate logistic analysis showed that multiple LVLs (OR 3.1: 95% CI[1.1, 8.5]; p = 0.03) was an independent risk factor for local recurrence after EMR. The cumulative local recurrence rates at 3 years in patients with multiple LVLs and those without multiple LVLs were 39% and 14% (p < 0.01), respectively. All of the recurrent lesions except two could be removed by EMR, which was not associated with any serious complication. The remaining two patients had chemoradiotherapy. Overall cause-specific survival at 3 years was 100%. CONCLUSIONS: Patients with multiple LVLs are at risk of local recurrence after EMR. Although careful long-term endoscopic follow-up is needed for such patients, EMR is potentially curative for recurrent lesions.

Adult↗

PubMed2005

Photodynamic therapy as salvage treatment for local failures after definitive chemoradiotherapy for esophageal cancer.

BACKGROUND: Although definitive chemoradiotherapy for esophageal cancer shows a high response rate, persistent or recurrent locoregional disease remains a major problem. Salvage esophagectomy is the only curative intent treatment option; however, it carries higher morbidity and mortality rates than primary esophagectomy. Response to second-line chemotherapy is quite dismal. METHODS: From December 2002 to November 2003, we applied salvage photodynamic therapy to 13 patients with local failures after completion of chemoradiotherapy, 4 patients had local recurrence after achieving a complete response, and 9 had a persistent tumor after chemoradiotherapy. The decision to treat was based on patients' refusal of salvage surgery or chemotherapy. After the intravenous administration of 2 mg/kg of Photofrin, photoradiation treatment with an excimer dye laser was performed for 48 hours and 72 hours after the injection. Written informed consent was obtained from all patients. RESULTS: Eight patients (62%) achieved a complete response. After a median follow-up period of 12 months after photodynamic therapy, 6 patients were still free of disease, and the overall survival rate at 1 year was 68.4%. There were no treatment-related deaths. CONCLUSIONS: Our results show that salvage photodynamic therapy could be a promising curative intent treatment option with low morbidity and mortality rates.

Aged↗

PubMed2005

Narrow band imaging: a new diagnostic approach to visualize angiogenesis in superficial neoplasia.

Although numerous gastrointestinal endoscopes pass through the oropharynx and the hypopharynx, it is extremely difficult to detect an early cancer in these sites during routine endoscopic examination. Most patients with cancer in these sites are usually diagnosed in advanced stages. If effective screening methods can detect an earlier stage, such as carcinoma in situ, it would obviously be of great benefit. Narrow band imaging is an innovative optical technology that can clearly visualize the microvascular structure of the organ surface. Herein, we demonstrate that narrow band imaging combined with magnifying endoscopy can identify a carcinoma in situ in oropharyngeal and hypopharyngeal mucosal lesions. Scattered irregular foci of microvascular proliferation projecting to the dysplastic squamous epithelium are the typical features. These results indicate that an approach to visualize angiogenesis or morphologic changes of microvessels in the superficial neoplasm can be a new diagnostic method not only for the head and neck region but also for other sites in the gastrointestinal tract.

Capillaries↗

PubMed2005

Mean corpuscular volume, alcohol flushing, and the predicted risk of squamous cell carcinoma of the esophagus in cancer-free Japanese men.

BACKGROUND: Because some of the causes of increased mean corpuscular volume (MCV) and esophageal squamous cell carcinoma (ESCC), including alcoholism, acetaldehyde exposure, smoking, and poor nutrition are common to both, macrocytosis has been used as a predictor of early ESCC in Japanese alcoholics. We examined whether this was also true in the Japanese general population. METHODS: This study compared the MCV of 522 cancer-free Japanese men with his risk of ESCC as defined using drinking, smoking, dietary habits and aldehyde dehydrogenase-2 (ALDH2) genotype in a previous case-control study of ESCC involving them as control subjects. RESULTS: MCV was significantly correlated with ESCC risk predicted by drinking combined with ALDH2 genotype, smoking, or fruit intake. Men at higher risk of ESCC were more frequent in the groups with higher MCV (p < 0.0001 for trend). The replies to a questionnaire about facial flushing in response to alcohol showed that the trend was more prominent in men with current/former flushing, a surrogate marker for inactive ALDH2, than in men with no flushing (p < 0.0001). In comparison with the mean risk of men with MCV < or = 93 fl (lowest quartile), that of current/former flushing men with MCV > or = 99 fl (highest quartile) was 6.35-fold higher, whereas that of never-flushing men with MCV > or = 99 fl was 2.50-fold higher. The sensitivity and specificity of the combination of moderate-to-heavy drinking and either MCV > or = 99 fl or current/former flushing, either 30+ pack-years or MCV > or = 99 fl or either 30+ pack-years or current/former flushing for detection of high-risk persons ranking in the top 10%, was 85% and 84%, 94% and 76%, or 98% and 77%, respectively. CONCLUSIONS: MCV and alcohol flushing might be used to better select candidates to screen this high-mortality-rate cancer not only in alcoholics but also in nonalcoholic Japanese men.

Adult↗

PubMed2004

Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites.

BACKGROUND: Head and neck squamous cell carcinoma typically is diagnosed at an advanced stage, and the prognosis for patients with this type of malignancy is poor. Detection of these lesions at an earlier stage (e.g., as carcinoma in situ) would be of clear benefit to patients. However, it has been extremely difficult to detect carcinoma in situ at head and neck mucosal sites during routine endoscopy, even after numerous passes of the endoscope through the oral cavity and the pharynx. METHODS: The current clinical investigation was performed during routine endoscopic screening or surveillance procedures. The authors used a novel optical technique, known as narrowband imaging (NBI) that allows noninvasive visualization of the microvascular structure of an organ's surface using reflected light. RESULTS: Between April 2002 and August 2003, 34 consecutive superficial lesions were found in 18 patients. Multifocal carcinoma was found in 5 patients (28%). The median age of the patients examined was 59.5 years (range, 43-71 years), and 83% of all patients were male. All lesions exhibited a microvascular proliferation pattern on magnified NBI. Thirteen patients with a combined total of 29 lesions underwent endoscopic resection under general anesthesia. The pyriform sinus was the most frequent primary site (66%; 19 of 29 lesions). The median tumor diameter was 20 mm (range, 1.3-40 mm). Twenty-one lesions (72%) were histologically confirmed to be carcinoma in situ, and the remaining lesions showed evidence of microinvasion (0.05-1 mm) beneath the epithelium. Vascular invasion was observed in only one lesion. The median hospital stay was 10 days (range, 4-18 days). All patients were discharged without severe complications. After a median follow-up period of 8 months (range, 1-16 months), there were no cases of local disease recurrence. CONCLUSION: The authors stress the importance of endoscopic detection of superficial carcinoma at oropharyngeal and hypopharyngeal mucosal sites. NBI is a promising and potentially powerful tool for identifying carcinomas at an earlier stage during routine endoscopic examination.

Adult↗

PubMed2004

Frequent and preferential infection of Treponema denticola, Streptococcus mitis, and Streptococcus anginosus in esophageal cancers.

Multiple cancers frequently occur in the upper digestive tract. One possible explanation is that specific bacterial infection stimulates the normal epithelium to initiate inflammation and/or promotes carcinogenesis. This study was undertaken to determine which bacterial species is predominantly associated with esophageal cancer. We examined the bacterial diversity in this type of cancer and in the saliva from healthy people by using a culture-independent molecular method. Here we report the preferential and frequent infection of the oral periodontopathic spirochete Treponema denticola (T. denticola), Streptococcus mitis (S. mitis), and Streptococus anginosus (S. anginosus) in esophageal cancer from different regions of the world, and we also describe the induction of inflammatory cytokines by infection of S. anginosus and S. mitis. Our present data suggest that these three bacteria could have significant roles in the carcinogenic process of many cases of esophageal cancer by causing inflammation and by promoting the carcinogenic process, and that eradication of these three bacteria may decrease the risk of recurrence.

Blotting, Northern↗

PubMed2003

Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T(2-3)N(any) M(0) squamous cell carcinoma of the esophagus.

PURPOSE: To compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus and to identify useful clinicopathologic and biologic markers to select better treatment. METHODS AND MATERIALS: Between August 1992 and April 1999, 98 consecutive patients were selected for this study; 53 were treated with chemoradiotherapy and 45 with surgery. The patients in the chemoradiotherapy group received 5-fluorouracil combined with cisplatin plus 60 Gy of radiation, and those in the surgery group received an esophagectomy with radical node dissection. Biologic markers were investigated immunohistochemically using pretreatment biopsy specimens. RESULTS: The baseline clinical TNM stage was more advanced in the chemoradiotherapy group than in the surgery group. With a median follow-up period of 43 months, the 5-year survival rate was 46% in the chemoradiotherapy and 51% in the surgery group, without statistical significance (p = 0.47, log-rank test). Cox regression analysis for prognosis revealed that epidermal growth factor receptor positivity, high microvessel density, and cyclin D1 positivity yielded a low value for relative risk (0.66, 0.54, and 0.62, respectively), which favored chemoradiotherapy over surgery, without statistical significance. CONCLUSION: This nonrandomized study showed a trend for the chemoradiotherapy in the treatment of esophageal carcinoma, but the results need to be confirmed by additional study.

Adult↗

PubMed2003

Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus.

PURPOSE: To assess the long-term toxicity after definitive chemoradiotherapy (CRT) for squamous cell carcinoma (SCC) of the esophagus. PATIENTS AND METHODS: Patients newly diagnosed with SCC of the esophagus and treated with definitive CRT between 1992 and 1999 in our institution were recruited from our database on the basis of the following criteria: age </= 75 years, performance status (PS; based on the Eastern Cooperative Oncology Group scale) 0 to 2, and clinical tumor-node-metastasis system stage I to IVA. The CRT consisted of two cycles of cisplatin 40 mg/m2 on days 1 and 8, and continuous infusion of fluorouracil 400 mg/m2/d on days 1 to 5 and 8 to 12, repeated every 5 weeks with concurrent radiotherapy of 60 Gy in 30 fractions. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme was adopted. RESULTS: A total of 139 patients were recruited, and their characteristics were as follows: median age, 62 years (range, 38 to 75 years); 121 males and 18 females; 96 patients PS 0, 42 patients PS 1, and one patient PS 2; 15 patients T1, 11 patients T2, 60 patients T3, and 53 patients T4; and 101 patients M0, 38 patients M1a. With a median follow-up of 53 months, the median survival time and 5-year survival rate were 21 months and 29%, respectively. Of 78 patients with complete remission, two patients died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in eight patients, seven patients, and one patient, respectively; heart failure in zero, zero, and two patients; pleural effusion in seven, eight, and zero patients; and radiation pneumonitis in one patient, three patients, and zero patients, respectively. CONCLUSION: Definitive CRT for SCC of the esophagus is effective with substantial toxicities. Additional investigation to minimize the normal tissue toxicities is warranted.

Adult↗

PubMed2003

Efficacy and safety profile of S-1 in patients with metastatic gastric cancer in clinical practice: results from a post-marketing survey.

BACKGROUND: S-1(TS-1), a novel oral fluoropyrimidine, has been commercially available for gastric cancer in Japan. A nationwide post-marketing survey for safety was carried out after its approval. The aim of this analysis was to evaluate the efficacy and safety profile of this agent in clinical practice for patients with advanced gastric cancer registered in the postmarketing survey from our institution. METHODS: Between April 1999 and April 2000, a total of 51 chemo-naive patients were registered in the survey from the National Cancer Center Hospital East. S-1 was administered at 80 mg/m2/day for 4 weeks, followed by a 2-week rest, repeated every 6 weeks until disease progression, unacceptable toxicity, or the patient's refusal. RESULTS: Of the 51 patients, 41 (80%) fulfilled the criteria of the guidelines determined by the company as appropriate patients for the drug administration. The median number of treatment courses was five. Toxicities were generally mild: grade 3 or 4 toxicities were seen in 10% or fewer patients, and no treatment-related deaths occurred. In the 47 patients with evaluable lesions, there were 2 complete responses and 18 partial responses, with a response rate of 43%. With a minimum follow-up of 2 years, median survival time and 2-year survival were 11.1 months and 33%, respectively. The majority of the 17 2-year survivors had diffuse-type histology and peritoneal metastasis and achieved an objective response. CONCLUSION: S-1 appears to be safe and highly active, with favorable longterm survival in patients with metastatic gastric cancer, particularly in those with diffuse-type histology and peritoneal metastasis.

Adenocarcinoma↗

PubMed2003

EMR as salvage treatment for patients with locoregional failure of definitive chemoradiotherapy for esophageal cancer.

BACKGROUND: Definitive chemoradiotherapy is recognized as a standard treatment for esophageal cancer. Although most failures of this combined modality are locoregional, without distant metastasis, there are few curative treatment options available in such cases except salvage esophagectomy. METHODS: Experience with 16 patients with squamous cell carcinoma of the esophagus who underwent EMR as a salvage treatment after locoregional failure of definitive chemoradiotherapy was reviewed retrospectively. EMR was performed by using the mucosal strip technique. Eight patients had local recurrence at the primary site after a complete response to chemoradiotherapy, 5 had metachronous multiple cancers, and 3 had residual tumor after completing chemoradiotherapy. RESULTS: In all patients, the EMR-treated tumors were histopathologic stage T1 and were clinical stage N0M0 as defined by EUS and CT. No serious complication was observed in any patient. At a median follow-up of 33 months (range 11-73 months) from the initiation of chemoradiotherapy, 3 patients (38%) with local recurrence at the primary site, 3 (40%) with metachronous multiple cancers, and two (67%) with residual cancer were still alive and disease-free after salvage EMR, for periods of 30 to 63 months. The 3-year survival rate from the initiation of salvage EMR for all patients was 56%. CONCLUSIONS: Long-term survival can be achieved with salvage EMR for locoregional failure after definitive chemoradiotherapy for esophageal cancer without serious complications. EMR may be a salvage treatment option when a recurrent or residual tumor is superficial or local.

Adult↗