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T Mitsudomi

Publications and source records attributed to T Mitsudomi.

At least 73 records · Page 4Linked to original sources
PubMed1995

Video-assisted thoracoscopic surgery of bullous and bleb disorders of the lung using endoscopic stapling device.

The video-assisted thoracic surgical (VATS) approach appears to be a viable alternative to thoracotomy when surgical management of bullous and bleb disorders of the lung is required. Fifty patients with giant bullae (n = 6) and spontaneous pneumothoraces (n = 44) were recently treated by our group using the VATS approach and endoscopic stapling devices. Of the 50 patients, 47 were managed completely by the VATS approach, including six giant bullae that were asymptomatic in five and infectious in one and 41 pneumothoraces, of which 16 were first episode and 25 with recurrent pneumothorax. Median operating times for the bullous and bleb excisions were 147.8 and 45.9 min, respectively (p < 0.01), and median chest tube durations were 5.2 and 1.2 days, respectively (p < 0.05). There was no mortality, and significant morbidity was limited to prolonged air leak in more than 5 days in three patients and postoperative atelectasis in two patients. Median hospital stays of patients with bullous excision was 11.3 days compared with 4.7 days of those with bleb excision. We conclude that the VATS treatment is a safe, effective procedure in patients with bullous and bleb disorders of the lung even in asymptomatic giant bullae or spontaneous pneumothoraces with the first episode. The advantages of the VATS approach for these diseases are ease of operation, less pain, early mobility, and superior cosmetic results.

Adolescent↗
PubMed1994

Genetic analysis of the catalytic domain of the GAP gene in human lung cancer cell lines.

Cell lines of non-small cell lung cancer (non-SCLC) have been shown to contain activating mutation of the K-ras oncogene in about 30% of cases, whereas no small cell lung cancer (SCLC) cell lines displayed these mutations. Biochemically, these mutations result in the ras gene product (p21) being constitutively activated in its GTP-bound form and insensitive to the hydrolytic action of the ras-specific GTPase-activating protein (ras GAP). We hypothesized that, if tumor development is related to the p21 ras being in the active GTP-bound state, then a similar malignant phenotype may result from an inactivating mutation in the ras GAP gene in the region that interacts with ras p21 (so-called catalytic domain). To test this hypothesis, we screened a panel of SCLC and non-SCLC cell lines for major genetic alterations in the catalytic domain of the GAP gene with the Southern blot technique, and for minor genetic abnormalities (e.g., point mutations) with denaturing gradient gel electrophoresis and single-strand conformation polymorphism. Mutations in the catalytic domain of the GAP gene could not be demonstrated by any technique in any cell line examined. We conclude that mutational inactivation of the catalytic domain of the GAP gene probably does not contribute to the development of lung cancer.

Blotting, Southern↗
PubMed1994

Efficiency of serum copper/zinc ratio for differential diagnosis of patients with and without lung cancer.

We examined serum copper (Cu), serum zinc (Zn), and the serum copper/zinc ratio (Cu/Zn) in 162 patients. All of them were seen to have an abnormal shadow in the chest X-ray films, that is, 109 patients with lung cancer (LC) and 53 patients with no lung cancer (NLC). The mean Cu and Cu/Zn in LC patients were significantly higher than those in NLC patients (p < 0.05). In LC patients, Cu and Cu/Zn were higher and Zn was lower in advanced tumors than early ones. There was a significantly clear relation between Cu or Cu/Zn and the tumor (T) stages. When the relative risk (RR) of LC was estimated, it was seen that the higher Cu and Cu/Zn became, the higher RR became. Furthermore, we showed the sensitivity of the receiver operator characteristic of the test (ROC) curve for Cu, Cu/Zn, and carcinoembryonic antigen (CEA) to diagnose LC, as explained in a paragraph of methods. The determinations of Cu, Zn, and Cu/Zn are simple and inexpensive. They also appear to have a great diagnostic value in determining the local invasion of LC and as a screening test in the high-risk patients for LC.

Adult↗
PubMed1994

Surgical treatment of lung cancer in the octogenarian.

The purpose of this study was to investigate the value of surgical treatment for lung cancer in the octogenarian. Thirty-three patients 80 years of age or older (mean age, 82.4; range, 80 to 92 years; 25 men, 8 women) underwent surgical resection in our units between 1974 and 1991. The operative mortality rate was 3%, and the 5-year survival rate was 32%. The relative 5-year survival rate (survival rate of our subjects/that of matched population) was 61%. The mortality and long-term survival rates were similar to those in younger patients. In this study, long-term survival had no significant dependence on stage of disease, histologic tumor type, or complete versus incomplete resection. It was dependent mainly on postoperative complications, in particular, cardiorespiratory complications (cardiac complications, p = 0.0005; respiratory complications, p < 0.05). These data suggest that the octogenarian who suffers from lung cancer deserves the opportunity for a cure and the long-term benefits of surgical treatment, on the condition that no postoperative major cardiorespiratory complications set in.

Aged↗
PubMed1994

Integrated clinical and basic studies related to circumventing non-small cell lung cancer drug resistance.

Consideration of a range of clinical and basic studies conducted at the National Cancer Institute which explore the nature of the tumor biology of lung identify the limitations of using chemotherapy for the treatment of advanced lung cancer. No single mechanistic explanation for lung cancer's chemoresistance is apparent, although considerable information about the biology of lung cancer and some of its clinical consequences have been elucidated. In contrast to previous works from our group, this presentation will focus principally on studies of the nature of drug resistance with non-small cell cancer. An alternative combined modality strategy for lung cancer control is to focus on epithelial progression of lung cancer using local modalities while it is still confined to the bronchial epithelium. Particular high risk populations may be appropriate to determine if local tools such as photodynamic laser therapy can be effective in this application. To deal with the underlying biochemical perturbations resulting from critical exposure of the bronchial epithelium to carcinogens, rational biochemical intervention with 13 cis retinoic acid are being evaluated in several clinical trials. An evolution towards more effective lung cancer control may involve the combined modalities of laser ablation of accessible dysplastic epithelium and chronic administration of intervention agents, such as retinoids, to neutralize cancer promotion dynamics in the more remote areas of the lung epithelium.

Antineoplastic Agents↗
PubMed1994

Combined thoracoscopy and mediastinoscopy for the evaluation of mediastinal lymph node metastasis in left upper lobe lung cancer.

Cervical mediastinoscopy has an important but limited role in the evaluation of mediastinal adenopathy of the aorticopulmonary window in patients with left lung cancer. Thoracoscopy is another valuable diagnostic procedure in the assessment of mediastinal adenopathy. Combined thoracoscopic and mediastinoscopic evaluation may be more accurate for assessing mediastinal lymph node metastasis in left lung cancer than either procedure alone.

Adenocarcinoma↗
PubMed1994

p53 immunostaining positivity is associated with reduced survival and is imperfectly correlated with gene mutations in resected non-small cell lung cancer. A preliminary report of LCSG 871.

We investigated the correlation of p53 abnormalities with survival in 85 patients with non-small cell lung cancer (NSCLC) who had undergone resection with curative intent as part of Lung Cancer Study Group (LCSG) 871. Our previous studies showed that only a subset of p53 mutations in lung cancers result in overexpression. In addition, protein overexpression has been described in the absence of mutation. Therefore, we determined both p53 protein overexpression (by immunostaining) and p53 and ras gene mutations (by single-strand conformation polymorphism and DNA sequencing) in this set of resected tumor specimens. Clinical follow-up data were available for 75 cases. Of the studied patients, 64% showed p53 overexpression and 51% had mutant p53 sequences; however, the concordance rate was only 67%. There was a negative survival correlation with positive p53 immunostaining (p = 0.05), but not with the presence of gene mutations (p = 0.62) in this group of patients. Overexpression of p53 protein determined by immunostaining may contribute to adverse outcome due to the ability of p53 to act as a dominant oncogene, or alternatively, overexpression may reflect ongoing DNA damage in the tumor as a marker for a more aggressive behavior. When adjusted for stage, age, and gender by multivariate analysis, however, there was no independent impact of p53 overexpression on survival.

Adult↗
PubMed1994

Polymorphism at codon 36 of the p53 gene.

A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

Base Sequence↗
PubMed1993

Mutations of the p53 gene as a predictor of poor prognosis in patients with non-small-cell lung cancer.

BACKGROUND: Inactivation of the p53 tumor suppressor gene (also known as TP53) through a point mutation and/or loss of heterozygosity is one of the most common genetic changes found in various types of human tumors. PURPOSE: Our purpose was to investigate the relationship between the presence of p53 gene mutations and survival of patients with non-small-cell lung cancer (NSCLC) of all stages who underwent surgery with preoperative curative intent as a routine therapeutic intervention. The prognostic significance of factors like sex, age, tumor histology, and the stage of the disease was also evaluated. METHODS: We analyzed 120 tumor specimens from patients with histologically confirmed NSCLC for p53 mutations occurring in exons 5 through 8 by polymerase chain reaction-single-strand conformation polymorphism assay of genomic DNA. Univariate and multivariate analyses were performed to assess the association between p53 mutations and the survival of the NSCLC patients. RESULTS: Fifty-one (43%) of 120 tumor specimens showed p53 mutations. Overall, the p53 mutations did not correlate with sex, age, or the clinical stage of the disease but showed frequent association with tumors of squamous cell histology. Univariate analysis revealed that the patients with p53 mutations survived for a significantly shorter period of time after surgery than those without the mutations (P = .0100, logrank test). The presence of p53 mutations was a significant prognostic factor in the patients with advanced disease (stages IIIA through IV) (P = .0091) but not in those with early disease (stages I and II) (P = .2837). Multivariate analysis using the Cox proportional hazards model found independent prognostic significance for p53 mutations (hazards ratio [HR] = 1.84; P = .018) and advanced disease stage (HR = 2.20; P = .003). The model also predicted the lower risk for female patients (HR = 0.51; P = .040). CONCLUSION: The occurrence of p53 mutations in some NSCLC tumors may be independently associated with a shortened overall survival and may be of somewhat more prognostic significance in patients with advanced stage than in those with early stage of the disease. IMPLICATION: Detection of p53 mutations may help in the selection of NSCLC patients suitable for appropriate investigational therapeutic strategies in view of improving their survival and quality of life.

Aged↗
PubMed1993

Correlation of intrinsic chemoresistance of non-small-cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations.

BACKGROUND: At diagnosis, most small-cell lung cancers (SCLCs) are chemosensitive, whereas non-small-cell lung cancers (NSCLCs) are usually chemoresistant. Activation of ras genes and HER-2/neu genes (also known as ERBB2) is encountered in subpopulations of NSCLC but not in SCLC and has been linked to shortened survival. Therefore, activation of these genes may be associated with intrinsic chemoresistance in NSCLC. Studies have also suggested that the multidrug-resistant phenotype expressed by the MDR1 gene (also known as PGY1) does not correlate with the in vitro chemosensitivity of NSCLC cells or with clinical response to therapy and does not explain the spectrum of cross-resistance to drugs. PURPOSE: The purpose of this study was to investigate the relationships between chemoresistance and the presence of ras gene point mutations and overexpression of the HER-2/neu gene in NSCLC cell lines, which indicates gene activation. METHODS: Using a panel of 20 NSCLC cell lines established from untreated patients, we assessed the differences in HER-2/neu messenger RNA (mRNA) expression in the cell lines with or without ras mutations. We performed in vitro drug sensitivity testing by the tetrazolium-based MTT [i.e., 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide] assay with doxorubicin, carmustine, cisplatin, melphalan, mitomycin, and etoposide, and we determined the differences in IC50 values (i.e., the drug concentrations required to inhibit cell growth by 50%) for the cell lines. RESULTS: We found a statistically significant correlation between the IC50 values for all six drugs and the degree of HER-2/neu gene expression in all 20 cell lines (r = .67-.86; P < .005) as well as in the subpopulation of eight cell lines with ras mutations (r = .83-.98; P < .05). The IC50 values for doxorubicin, carmustine, cisplatin, and melphalan were not significantly different in the cell lines with or without ras mutations, but the values for mitomycin and etoposide in lines with ras mutations were slightly lower than in those without ras mutations (borderline significance, P = .031). Levels of HER-2/neu expression in cell lines with ras mutations were lower than those without ras mutations, but the difference was not statistically significant. CONCLUSION: Our findings indicate that overexpression of HER-2/neu is a marker for intrinsic multidrug resistance in NSCLC cell lines. IMPLICATIONS: If the clinical relevance of our findings is confirmed, HER-2/neu gene expression can be used as a predictor of therapeutic failure in NSCLCs. The relationships between HER-2/neu gene expression, cell proliferation, and chemoresistance in NSCLC require further investigation.

Antineoplastic Agents↗
PubMed1993

Giant hamartoma of the lung with a high production of carbohydrate antigen 19-9.

A rare case of a giant pulmonary hamartoma with a high production of carbohydrate antigen (CA) 19-9 is presented. A 43-year-old woman with complaints of cough, fever, and chest pain was diagnosed as having a posterior mediastinal tumor with pneumonia. The serum CA 19-9 level was high. A thoracotomy revealed an intrapulmonary solid mass with a histologic diagnosis of cartilaginous hamartoma with no evidence of malignancy. The CA 19-9 concentration in the mucus of the tumor was high, and postoperatively the serum CA 19-9 level returned to normal. The CA 19-9 could be immunohistochemically demonstrated on the surface of the tumor.

Adult↗
PubMed1993

Nucleolar organizer regions are independently associated with a shortened survival in patients with non-small cell lung cancer.

We examined nucleolar organizer regions (Ag-NOR) in 102 patients with non-small cell lung cancer (NSCLC). Ag-NOR counts were generally higher in tumours from more advanced stages, or in poorly differentiated adenocarcinomas. Six potential-prognostic indicators included sex, age, year of operation, histology, stage and Ag-NOR count. Stage and Ag-NOR counts had a significant prognostic value in the univariate analysis for 79 patients who died of their lung cancer. In the multivariate analysis, high Ag-NOR counts as well as disease stage were independently associated with a poor prognosis. Furthermore we divided patients into three groups according to their Ag-NOR counts and found that in patients with stage I and II disease higher Ag-NOR counts were associated with shortened survival. This trend did not continue in patients with stage III and IV disease.

Adenocarcinoma↗
PubMed1993

Angiosarcoma of the chest wall with a gastric metastasis.

A rare case of chest-wall angiosarcoma with high tendency of local recurrence and with a solitary gastric metastasis is reported. The patient was an 84-year-old man who had a left lateral thoracic mass with a colic pain. The histological diagnosis of a biopsied specimen suggested an angiosarcoma. The first resection was performed, the resected specimen consisted of the 8th, 9th and 10th ribs including the tumor. However the tumor recurred around the primary site and the second resection was undertaken eight months after the first resection. Only three months after the second resection a second chest-wall recurrence together with a solitary gastric metastasis was found. Progressive emaciation, anemia and thrombocytopenia became evident, and the patient died the 40th day after the gastrectomy. Primarily a wide resection of the chest wall beyond the pathologically negative region around the tumor is thought to be necessary.

Aged↗
PubMed1993

Detection and sequencing of p53 gene mutations in bronchial biopsy samples in patients with lung cancer.

We demonstrated the feasibility of detection of p53 gene mutations in bronchial biopsy samples from patients with lung cancer. Following DNA extraction from two to three pieces of bronchial tissue obtained by fiberoptic bronchoscopy, p53 gene mutations were screened using polymerase chain reaction/single-strand conformation polymorphism technique. We examined four bronchial biopsy specimens from patients with squamous cell carcinoma of the lung and detected one point mutation at codon 130 (C to G, Leu to Val). This technique will be very useful for studies on early detection of lung cancers or for an analysis of a suspected premalignant lesion. Furthermore, this technique enables us to know the status of oncogene or tumor suppressor gene at the time of diagnosis, which may be very useful for a treatment of patients with cancer in the not too distant future.

Aged↗
PubMed1993

Aspergilloma within cavitating pulmonary carcinoma. Case report.

Aspergillosis was diagnosed in a 69-year-old man presenting with blood-stained sputum, and was treated with an antifungal agent. As radiographic lesions persisted after 3 months, left upper lobectomy was performed. The surgical specimen revealed pulmonary carcinoma associated with an intracavitary aspergillar infection.

Aged↗