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T Iizasa

Publications and source records attributed to T Iizasa.

At least 19 recordsLinked to original sources

Transbronchial fine needle aspiration cytological examination: a useful tool for diagnosing primary lung cancer.

BACKGROUND: Obtaining a definitive preoperative diagnosis plays a critical role in deciding upon the treatment approach for lung carcinoma. However, success in making definitive diagnoses of small primary lung cancers will require new approaches because these cancers are difficult to detect using standard biopsy procedures. METHODS: We evaluated the results of morphologic definitive diagnosis together with various clinical factors in 1003 primary lung cancers resected surgically. Patients underwent transbronchial brushing, fine needle aspiration cytology, forceps biopsy, and/or forceps biopsy-stamp cytology for preoperative diagnoses, in conjunction with the use of Diff-Quik to confirm that hits had been made on the radiographic shadows before terminating the examinations. RESULTS: Sensitivities of the diagnostic procedures for primary lung cancers were as follows: 64.8% for brushing, 56.1% for transbronchial forceps biopsy, 72.0% for transbronchial forceps biopsy-stamp cytology, and 86.4% for transbronchial fine needle aspiration. The four transbronchial biopsy procedures had a combined overall sensitivity of 92.7%. In patients with peripheral lung cancers of 2 cm or less in diameter, transbronchial fine needle aspiration had a sensitivity of 75.9%, which was the highest sensitivity for all transbronchial examinations. In the subset of 296 patients who underwent all four transbronchial biopsy examinations, transbronchial fine needle aspiration had the highest sensitivity of preoperative diagnosis of all the transbronchial examination methods. CONCLUSIONS: The sensitivity of preoperative cytological diagnosis for primary lung cancers, especially transbronchial aspiration cytology, is high. Transbronchial fine needle aspiration cytology is useful for the preoperative diagnosis of primary lung cancer.

Adolescent↗

DNA methylation-associated inactivation of TGFbeta-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers.

The transforming growth factor beta (TGFbeta)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFbeta signalling, and RUNX3, which facilitates TGFbeta-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n=13). Methylation percentages of the three genes ranged from 0-83% in adult tumours and 0-50% in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFbeta-related genes are frequently deregulated through aberrant methylation in many human malignancies.

Aged↗

Aberrant methylation of SPARC in human lung cancers.

SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca2+-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinicopathological features. We observed loss of SPARC expression in 12 of 20 (60%) lung cancer cell lines. Treatment of expression-negative cell lines with a demethylating agent restored expression in all cases. Methylation frequencies of SPARC gene were 55% in 20 lung cancer cell lines. Primary tumours had methylation at a rate of 69% (119 of 173), while nonmalignant lung tissues (n=60) had very low rates (3%). In lung adenocarcinomas, SPARC methylation correlated with a negative prognosis (P=0.0021; relative risk 4.65, 95% confidence interval 1.75-12.35, multivariate Cox's proportional-hazard model). Immunostaining revealed protein expression in bronchial epithelium (weak intensity) and in juxtatumoral stromal tissues (strong intensity) accompanied by frequent loss in cancer cells that correlated with the presence of methylation (P<0.001). Our findings are of biological interest and potentially of clinical importance in human lung cancers.

Adenocarcinoma↗

Frequency of loss of heterozygosity at 3 p, 9 p, 13 q, and 17 p is related to proliferative activity in smokers with stage I non-small cell lung cancer.

BACKGROUND: Tumor cells of lung cancer exhibit genetic abnormalities as well as high proliferative activity. The purpose of this study was to evaluate the relationship of genetic abnormalities and smoking status, histological type, and tumor proliferative activity in resected samples of stage I non-small cell lung cancer (NSCLC). METHODS: We evaluated 126 samples of stage I NSCLC from patients who underwent complete resection between 1988 and 1993. Loss of heterozygosity (LOH) was assessed using primers that amplified polymorphic microsatellite markers at D3S1300, D3S643, D3S1317, D9S171, IFNA, D13S153, and TP53. Expression of Ki-67 nuclear antigen was examined using immunohistochemical methods to assess tumor proliferative activity. RESULTS: The Fractional Regional Loss index (FRL) was significantly higher in squamous cell carcinoma samples than in adenocarcinoma samples (p < 0.0001). In smokers, Ki-67 labeling index (LI) in high-FRL cases was significantly higher than in low-FRL cases (p < 0.0001). CONCLUSION: The frequency of LOH at 3 p, 9 p, 13 q, and 17 p was related to proliferative activity in smokers with stage I non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

The relationship between aberrant methylation and survival in non-small-cell lung cancers.

The present study examined the relationship between methylation of five genes (p16(INK4a), RASSF1A, APC, RARbeta and CDH13) and patient survival in 351 cases of surgically resected lung cancers. While there was no relationship between the other genes and survival, p16(INK4a) methylation was significantly related to unfavourable prognosis in lung adenocarcinomas.

Adenocarcinoma↗

Clinicopathological analysis of clinical N0 peripheral lung cancers with a diameter of 1 cm or less.

BACKGROUND: The appropriateness of limited resection for small-sized lung cancer continues to be debated. It is not yet clear whether tumor size alone is a reliable indicator for limited resection. METHODS: From 1980 to 2002, 27 patients with clinical N0 peripheral lung cancers having diameters of 1 cm or less underwent pulmonary resection. Clinicopathological features of these cases were reviewed retrospectively. RESULTS: Histological analysis showed that there were 23 cases of adenocarcinoma (81.5 %), two large cell carcinomas (7.4 %), and two carcinoid tumors. Twenty-two cases were classified as pathological stage 1, one was stage II, and four were stage III. Four patients (14.8 %) had lymphatic vessel invasion, three (11.1 %) had lymph node metastasis, and two (7.4 %) had intrapulmonary metastasis. The 5-year disease-free survival rate was 76.6 %. CONCLUSIONS: It is impossible to predict the effectiveness of an intentional limited resection for lung cancer using only tumor size.

Adenocarcinoma↗

High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer.

BACKGROUND: We investigated the use of high magnification bronchovideoscopy combined with narrow band imaging (NBI) for the detailed examination of angiogenic squamous dysplasia (ASD). This was carried out in relation to bronchial vascular patterns with abnormal mucosal fluorescence in heavy smokers at high risk for lung cancer. METHODS: Forty eight patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light and fluorescence bronchoscopic examination was first performed. Observations by high magnification bronchovideoscopy with conventional white light were made primarily at sites of abnormal fluorescence, and then repeated with NBI light to examine microvascular networks in the bronchial mucosa. Spectral features on the RGB (Red/Green/Blue) sequential videoscope system were changed from the conventional RGB broadband filter to the new NBI filter. The wavelength ranges of the new NBI filter were B1: 400-430 nm, B2: 420-470 nm, and G: 560-590 nm. ASD tissues were also examined using a confocal laser scanning microscope equipped with argon-krypton (488 nm) and argon (514 nm) laser sources. RESULTS: The microvessels, vascular networks of various grades, and dotted vessels in ASD tissues were clearly observed in NBI-B1 images. Diameters of the dotted vessels visible on NBI-B1 images agreed with the diameters of ASD capillary blood vessels diagnosed by pathological examination. Capillary blood vessels were also clearly visualised by green fluorescence by confocal laser scanning microscopy. There was a significant association between the frequency of dotted vessels by NBI-B1 imaging and tissues confirmed as ASD pathologically (p=0.002). CONCLUSIONS: High magnification bronchovideoscopy combined with NBI was useful in the detection of capillary blood vessels in ASD lesions at sites of abnormal fluorescence. This may enable the discrimination between ASD and another pre-invasive bronchial lesion.

Adult↗

Subepithelial vascular patterns in bronchial dysplasias using a high magnification bronchovideoscope.

BACKGROUND: We have developed a method of high magnification bronchovideoscopy that enables improved observation of subepithelial vascular patterns of the bronchial mucosa. A study was undertaken to investigate the value of high magnification bronchovideoscopy in the detailed examination of dysplasia in the bronchial mucosa of patients with abnormal mucosal fluorescence. METHODS: Thirty one patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light examination was first performed under local anaesthesia and fluorescence bronchoscopy was also carried out using a light induced fluorescence endoscopy (LIFE) lung system. A high magnification bronchovideoscope (XBF 200HM2) was then used to examine the microvascular network in the bronchial mucosa at sites of normal and abnormal fluorescence and the images obtained were compared with pathological diagnoses from bronchial biopsy specimens. Vascular area ratios were calculated using image analysing apparatus. RESULTS: Vascular networks with regular patterns were observed at 20 of 22 abnormal fluorescence sites in biopsy specimens from patients with bronchitis. However, vascular networks with increased vessel growth and complex networks of tortuous vessels of various sizes were observed in 15 of 21 abnormal fluorescence sites in dysplasia specimens. There was a significant difference between bronchitis and dysplasia specimens (OR=25, 95% CI 5.5 to 113, p<0.0001). Mean vascular area ratios from 16 normal bronchial epithelium specimens with normal fluorescence, and 22 bronchitis and 21 dysplasia specimens with abnormal fluorescence were 0.054 (95% CI 0.039 to 0.07), 0.095 (95% CI 0.072 to 0.118), and 0.173 (95% CI 0.143 to 0.203), respectively. The results indicate a statistically significant increase in vascular area in the three groups (p<0.0001). CONCLUSION: Areas of increased vessel growth and complex networks of tortuous vessels in the bronchial mucosa detected using a high magnification bronchovideoscope at sites of abnormal fluorescence may enable discrimination between bronchitis and dysplasia.

Aged↗

Bronchopleural fistula after lung cancer surgery. Multivariate analysis of risk factors.

BACKGROUND: To elucidate retrospectively the risk factors for bronchopleural fistulae after lung cancer surgery. METHODS: The subjects were 1,177 patients with lung cancer who underwent surgery between 1983 and 1997. Twenty-two clinical factors were examined by logistic analysis. RESULTS: Bronchopleural fistulae were observed in 35 patients (32 males, 3 females) with a mean age of 64 years. Eighteen (51%) of 35 patients died of BPF-related complications. The significant risk factors obtained by univariate analysis were male gender, heavy smoking, current smoking, low level of %FVC, metastases to lymph nodes, squamous cell carcinoma, increased WBC, decreased albumin, advanced postsurgical stage, sleeve lobectomy, and resection of the right lower lobe or middle and lower lobe. The significant risk factors noted by multivariate analysis were heavy smoking (30 or more pack/years), current rather than past smoking, metastases to lymph nodes, decreased albumin (3.5 mg/dl or less), and resection of the right lower lobe or middle and lower lobe. CONCLUSIONS: The above risk factors must be taken into account before surgical techniques followed by adequate perioperative management are selected.

Adolescent↗

Increased telomerase activity and elevated hTERT mRNA expression during multistage carcinogenesis of squamous cell carcinoma of the lung.

BACKGROUND: Telomerase activation is believed to play a critical role in the immortalization of cells and carcinogenesis. Telomerase activity is undetectable in normal somatic cells (except for those cells undergoing proliferation) but is expressed in the majority of human tumors including lung carcinoma. The expression of hTERT mRNA has been found to be correlated with telomerase activity. In the current study, the authors analyzed telomerase activity and hTERT mRNA expression in preinvasive bronchial lesions using biopsy specimens obtained by fluorescence bronchoscopy. METHODS: The authors studied 150 bronchial biopsy specimens obtained by fluorescence bronchoscopy. The intensity of telomerase activity was determined by the fluorescence-based telomeric repeat amplification protocol method in 74 bronchial biopsy specimens (22 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 23 dysplasia cases, and 14 squamous cell carcinoma cases), and the level of hTERT mRNA was analyzed in another 76 specimens (24 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 20 dysplasia cases, and 17 squamous cell carcinoma cases) by real-time polymerase chain reaction. RESULTS: The mean values (+/- the standard deviation [SD]) of telomerase activity in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 6.2 +/- 7.5, 13.9 +/- 14.8, 18.5 +/- 20.8, and 54.5 +/- 22.3 U/microg protein, respectively. The upper limit of telomerase activity in normal bronchial epithelium or bronchitis was 21 U/microg protein (mean + 2SD). It is interesting to note that, 5 of 15 squamous metaplasia biopsies (33%), 8 of 23 dysplasia biopsies (35%), and all squamous cell carcinoma biopsies (100%) exhibited levels of telomerase activity that were > 21 U/microg protein. The mean levels of hTERT mRNA in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 891 +/- 840, 1936 +/- 1704, 3019 +/- 2607, and 12965 +/- 18008 copies/microg total RNA, respectively. Telomerase activity and hTERT mRNA expression were found to increase in proportion to the severity of histologic change from normal bronchial epithelium or bronchitis to squamous cell carcinoma. CONCLUSIONS: These results suggest that an increase in telomerase activity and hTERT mRNA expression are features of the early stages of the development of squamous cell carcinoma of the lung, with strong telomerase activity and hTERT mRNA expression being prominent during the latter stages.

Adult↗

Fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

BACKGROUND: A new strategy in the treatment of squamous cell carcinoma of the tracheobronchial tree is the detection and eradication of preinvasive bronchial lesions before they become invasive cancers. It is, however, difficult to detect preinvasive lesions by conventional white-light bronchoscopy alone. PURPOSE: we conducted a detailed investigation on the use of fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. METHODS: 64 participants with sputum cytology suspicious or positive for malignancy were examined with both white light and fluorescence bronchoscopy (LIFE group). Earlier to this study, before fluorescence bronchoscopy became available in our institute, 48 participants having sputum cytology suspicious or positive for malignancy were examined with white light bronchoscopy alone (control group). Biopsy specimens for pathological examinations were taken of all abnormal areas discovered by white light or fluorescence bronchoscopy examination. RESULTS: In sputum cytology suspicious or positive for malignancy, the diagnosis of preinvasive bronchial lesions was greatly enhanced in the LIFE group as compared with the control group (45 vs. 7 lesions). The percentage of participants with preinvasive bronchial lesions was also significantly higher in the LIFE group than in the control group (40.6 vs. 12.5%, P = 0.00087, respectively). CONCLUSIONS: Our study suggests that the use of fluorescence bronchoscopy in addition to conventional white-light examination could greatly enhance the detection and localization of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

Aged↗

Colonization with Schizophyllum commune of localized honeycomb lung with mucus.

We report a surgical case involving localized honeycomb lung with mucus, caused by colonization of a Schizophyllum commune, which displayed a tumorous shadow in the right upper mediastinum. A 74-year-old male with a history of tuberculosis in the 1970s was referred to Chiba University Hospital (Chiba, Japan) with an abnormal shadow evident in the chest roentgenogram. A transbronchial biopsy failed to yield a definite diagnosis. We resected the right upper lobe, which was found to contain a consolidative lesion filled with viscous mucus in the right upper lobe adjacent to the right upper mediastinum. Microscopic examination revealed a honeycomb lung formation with mucus in the destroyed space. Culture of the mucus yielded a whitish filamentous fungus, positively identified as S. commune. This is the first report of S. commune leading to a deposit of mucus and the formation of a consolidative lesion in the destroyed lung.

Aged↗

[Surgery for non-small cell lung cancer based on the T factor].

We review the indications of surgery in patients with non-small cell lung cancer (NSCLC) based on the T factor, focusing on peripheral small tumors, invasion to other organs, and the presence of malignant pleural effusion or intrapulmonary metastasis. While limited surgery in patients with peripheral, small-sized NSCLC preserves postoperative pulmonary function, the prospects for long-term survival are reduced due to the likelihood of recurrence, Novel prospective studies are being conducted to determine the indications for limited surgery in such patients which focus on histology, tumor size, and pulmonary function. In some patients with locally advanced disease, especially with invasion of the chest wall (T3), pericardium (T3), left atrium (T4), great vessel (T4), and carina (T4) and with malignant pleural effusion found intraoperatively and ipsilateral intrapulmonary metastasis, complete resection results in long-term survival. Thus surgery should be considered in patients without N2 disease.

Carcinoma, Non-Small-Cell Lung↗

Ki-67 immunostaining and other prognostic factors including tobacco smoking in patients with resected nonsmall cell lung carcinoma.

BACKGROUND: To estimate the effectiveness of expression of the tumor proliferative marker Ki-67 antigen (Ki-67) as a postoperative prognostic marker, the authors analyzed Ki-67 expression and its correlation with postoperative survival and other clinicopathologic factors, including preoperative smoking habits, in patients with resected nonsmall cell lung carcinoma (NSCLC). METHODS: A total of 156 patients with resected NSCLC at the study institution were investigated. Postoperative survival rates were estimated based on demographic and clinicopathologic factors, including Ki-67 expression and preoperative tobacco smoking habits. RESULTS: The overall postoperative 5-year survival rate in patients with high Ki-67 labeling indices (>/= 20%) was 39.6% compared with 67.7% in patients with low Ki-67 labeling indices. This finding was significant for all resected cases and for each pathologic disease stage (P < 0.05). The postoperative 5-year survival rate in patients with a history of heavy smoking (>/= 30 pack-years) was 47.6% compared with 62.5% for other patients (P = 0.027). This result was especially significant in patients with International Union Against Cancer Stage I disease and in patients with nonsquamous cell carcinoma (P < 0.03). The authors also observed a positive correlation between the Ki-67 labeling index and preoperative smoking habits (P = 0.0002). Multivariate analysis demonstrated that lymph node involvement, tumor differentiation, and Ki-67 labeling index were significant prognostic factors in NSCLC (P < 0.01). CONCLUSIONS: Tumor Ki-67 expression is a strong prognostic factor in NSCLC, especially adenocarcinoma. It may be hypothesized that tobacco mutagenicity may play a role in the growth and extension of NSCLC, which is one of the major impediments to postoperative survival in patients with a history of heavy smoking.

Aged↗

Antitumor cytotoxicity mediated by ligand-activated human V alpha24 NKT cells.

Human V alpha24 NKT cells bearing an invariant V alpha24J alphaQ antigen receptor, the counterpart of the murine V alpha14 NKT cells, are activated by the specific ligand, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner. Here, we demonstrate that the alpha-GalCer-activated V alpha24 NKT cells exert a potent perforin-dependent cytotoxic activity against a wide variety of human tumor cell lines. In addition, we demonstrate that V alpha24 NKT cells and dendritic cells (DCs) from melanoma patients are functionally normal, even in the tumor-bearing status. The potential use of alpha-GalCer-activated V alpha24 NKT cells and/or DCs from patients for cancer immunotherapy is discussed.

Adult↗

Prognostic factors in surgical treatment of solitary brain metastasis after resection of non-small-cell lung cancer.

Patients with brain metastasis after resection of non-small-cell lung cancer usually have poor prognosis. A few such patients, however, survive for long periods after surgical resection of brain metastases. To evaluate the prognostic factors in resection of solitary brain metastasis from non-small-cell lung cancer, we reviewed 24 cases undergoing resection of solitary brain metastasis after resection of the primary site from 1977 to 1993. The patient population consisted of 20 men and four women ranging in age from 40 to 75 years old (average, 57.8 years old). None of the patients had systemic metastasis except in the brain at the time of brain surgery. The overall survival rates were 12.5% at 3 years and 8.3% at 5 years after brain surgery. The longest survival periods were 11.5 years after brain surgery and 15.4 years after lung surgery. The interval between lung and brain surgery (< or =360 days vs. >360 days), differentiation of primary cancer (poor vs. moderate), size of primary site (< or =5.0 cm vs. >5.0 cm), and operation of primary site (lobectomy vs. pneumonectomy) significantly affected survival as shown by univariate analysis (P<0.05). Other clinical factors (age, gender, histology, T- and N-status, 'resectability with curative intent' of the primary site, location of the brain metastasis and postoperative radiation therapy) did not affect survival. Multivariate analysis using Cox's proportional hazards model indicated that an interval of more than 360 days between the two surgical procedures (hazard ratio = 0.2351, P = 0.0136) and lobectomy (hazard ratio = 0.5274, P = 0.0416) were independent prognostic factors. In conclusion, patients with solitary brain metastasis from non-small-cell lung cancer without other organ metastasis, in whom relapse in the brain occurred more than 1 year after resection of the primary site and in whom lobectomy was performed, should be treated surgically to maximize the chance of prolonged survival.

Adenocarcinoma↗

Case report. Localized pulmonary zygomycosis without pre-existing immunocompromised status.

Pulmonary zygomycosis rarely occurs without pre-existing immunocompromised disease. A 72-year-old male was found to have a nodular shadow (3 cm x 4 cm) in the right S8 and S9 on a chest X-ray. Right lower lobectomy was performed and histological examination of the resected material demonstrated pulmonary zygomycosis. Hyphae stained positively not only with Grocott-Gomori methenamine silver staining, but also with an anti-Rhizopus oryzae polyclonal antibody.

Aged↗

Smoking before surgery predicts poor long-term survival in patients with stage I non-small-cell lung carcinomas.

PURPOSE: The majority of lung carcinoma patients requiring resection have smoking habits prior to surgical treatment, and the correlation of smoking with postoperative complications is well known. However, few studies have investigated the correlation between long-term survival and cigarette smoking in patients with primary, resected lung carcinoma. We analyzed the relationship between clinical factors, including cigarette smoking before surgery, and 10-year survival in stage I non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Cigarette smoking habit and other factors influencing either the overall survival or the disease-specific survival rates of patients with stage I primary, resected NSCLC were evaluated according to the Cox proportional hazards model using a total of 369 patients with stage I-NSCLC. RESULTS: Comparison of the cause of death in patients with 30 or more pack-years and patients with less than 30 pack-years showed significant differences in the prevalence of recurrent disease and onset of nonmalignant disease. Multivariate analysis demonstrated significant correlations between overall survival and age and pack-years. Disease-specific survival showed significant correlations with age, tumor classification, and visceral pleural invasion. CONCLUSION: Smoking pack-years is an important clinical prognostic factor in evaluating overall long-term survival in patients with stage I primary, resected NSCLC.

Aged↗