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Shigeaki Ogura

Publications and source records attributed to Shigeaki Ogura.

17 recordsLinked to original sources
PubMed2005

Susceptibility to oxygen desaturation during bronchoscopy in elderly patients with pulmonary fibrosis.

BACKGROUND: Fiber-optic flexible bronchoscopy (FFB) is a frequently performed procedure for the diagnosis and treatment of pulmonary disorders. However, hypoxemia occasionally occurs during FFB. OBJECTIVES: We attempted to examine the causes of arterial oxygen desaturation during FFB. METHODS: We studied 336 patients who underwent FFB without intervention between June 1, 2001 and September 30, 2002. Arterial oxygen saturation (SpO2) was continuously monitored using oximetry with a recording system. We analyzed the relationship between a reduction in SpO2 during FFB and various clinical parameters or background lung diseases. RESULTS: Of the 336 patients, 73 (22%) had an episode of oxygen desaturation (SpO2 <90% over 10 s). Of patients over 80 years old, 55% had an episode of oxygen desaturation, which was significantly higher than 27% observed in the patients of 80 and less than 80 years old (p < 0.05). Patients with pulmonary fibrosis had a higher risk of desaturation (55%) compared to patients with other complications or patients without any complication (p < 0.05). Multivariable analysis revealed that both age and pulmonary fibrosis were independent predictors of oxygen desaturation. However, the majority of the patients (94%) did not require routine oxygen supplementation. CONCLUSION: Although FFB is safe and does not require oxygen supplementation in most cases, age over 80 years and pulmonary fibrosis are high risk factors for significant oxygen desaturation during FFB.

Adult↗
PubMed2005

Insertion and fixation of fiducial markers for setup and tracking of lung tumors in radiotherapy.

PURPOSE: Internal 1.5-mm fiducial markers were used in real-time tumor-tracking radiotherapy (RT) for lung cancer. The fixation rate of the markers using the bronchial insertion technique, reliability of the setup using markers around the target volume, dislocation of the markers after real-time tumor-tracking RT, and long-term toxicity of marker insertion were investigated. METHODS AND MATERIALS: Between July 2000 and April 2004, 154 gold markers were inserted into 57 patients with peripheral lung cancer. The distances between the implanted markers in 198 measurements in 71 set-ups in 11 patients were measured using two sets of orthogonal diagnostic X-ray images of the real-time tumor-tracking RT system. The distance between the markers and the chest wall was also measured in a transaxial CT image on 186 occasions in 48 patients during treatment planning and during follow-up. The median treatment time was 6 days (range, 4-14 days). RESULTS: In 115 (75%) of the 154 inserted markers, the gold marker was detected throughout the treatment period. In 122 markers detected at CT planning, 115 (94%) were detected until the end of treatment. The variation in the distances between the implanted markers was within +/-2 mm in 95% and +/-1 mm in 80% during treatment. The variation in the distances between the implanted markers was >2 mm in at least one direction in 9% of the setups for which reexamination with a CT scan was indicated. The fixation rate in the left upper lobe was lower than in the other lobes. A statistically significant relationship was found between a shorter distance between the markers and the chest wall and the fixation rate, suggesting that the markers in the smaller bronchial lumens fixed better than those in the larger lumens. A learning curve among the endoscopists was suggested in the fixation rate. The distance between the markers and the chest wall changed significantly within a median of 44 days (range, 16-181 days) after treatment. CONCLUSION: The fixation of markers into the bronchial tree was useful for the setup for peripheral lung cancer and had an accuracy of +/-2 mm during the 1-2-week treatment period. The relationship between the markers and tumor can change significantly after 2 weeks, suggesting that adaptive four-dimensional RT is required.

Adult↗
PubMed2005

Cytological characteristics of pulmonary large cell neuroendocrine carcinoma.

To establish cytological features of pulmonary large cell neuroendocrine carcinoma (LCNEC), we evaluated the cytological characteristics of LCNEC. Samples from 25 histologically confirmed LCNECs (14 touch imprint (TI) and 11 curettage) were analyzed. The findings were compared with those for seven small cell lung carcinomas. Cytological findings of TIs were as follows: Tumor cells were medium- to large-sized, round or polygonal, and nuclear polymorphism was observed. Some of the tumor cells had clearly identified cytoplasms, but naked nuclei were frequently observed. Nuclei were round, oval, or polygonal, and possessed thin and smooth nuclear membranes. The nuclear chromatin pattern was finely or coarsely granular. One or two nucleoli were observed in the nuclei, but were inconspicuous in some cases. Tumor cells appeared in clusters, and rosette formation was observed, but single cells were frequently observed also. Necrotic background and nuclear streaking were frequently observed. In brush or curettage specimens, the number of cells observed on a glass was small, but the findings were almost the same as those for the TI samples. TI samples have characteristic features, such as a neuroendocrine morphologic pattern, large cell size, abundant cytoplasm, finely or coarsely granular chromatin of the nucleus, and prominent nucleoli, and the diagnosis of LCNEC is possible. In brush or curettage specimen, the LCNEC diagnosis may be possible if a sufficient number of tumor cells are obtained.

Carcinoma, Neuroendocrine↗
PubMed2003

Bronchoscopic microsampling method for measuring drug concentration in epithelial lining fluid.

Direct measurement of the concentration of antimicrobial agents in bronchial epithelial lining fluid (ELF) would allow for a more informed approach to appropriate dosing of antimicrobial agents for respiratory tract infections. In this study, we determined the time versus concentration profile in ELF after an oral administration of levofloxacin, using recently developed bronchoscopic microsampling probes. These probes could be repeatedly and safely inserted through the fiberoptic bronchoscope in normal healthy volunteers. The concentration of levofloxacin in ELF was 43.4% of the corresponding serum value at 1 hour, reached the same level at 2 hours, decreased in a similar manner as that in serum, and returned to undetectable levels at 24 hours. It exceeded minimal inhibitory concentrations of Staphylococcus aureus (0.25 microg/ml), Klebsiella species (0.5 microg/ml), and Haemophilus influenzae (0.06 microg/ml) after 6 hours. The experimental procedure was well tolerated, and no complications were observed. In conclusion, bronchoscopic microsampling is a feasible and promising method for measuring antimicrobial concentrations in the target sites of respiratory tracts directly and repeatedly.

Adult↗
PubMed2003

Granulocyte-macrophage colony-stimulating factor gene-transduced tumor cells combined with tumor-derived gp96 inhibit tumor growth in mice.

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-based cancer cell vaccines have been shown to be potent inducers of antitumor immunity in several murine models, but the antitumor effects on established tumors have been minimal. Conversely, the major role of the heat shock protein gp96, localized in the endoplasmic reticulum (ER), is to act as a molecular chaperone to assist the folding of nascent polypeptide chains in the ER. gp96 derived from tumor cells elicits specific protective immunity against parental tumors, presumably through the transport of tumor-specific peptides to antigen-presenting cells and the maturation of dendritic cells (DCs). However, the therapeutic effects of tumor-derived gp96 on established tumors have not been promising. The present study analyzes the therapeutic effects of GM-CSF gene-transduced Lewis lung cancer (LLC/GM) cells combined with LLC-derived gp96 on established wild-type LLC tumors in immunocompetent C57BL/6 mice. Therapy with either irradiated LLC/GM cells or LLC-derived gp96 barely affected established LLC tumor growth. The antitumor effect was significantly enhanced when 1 microg of LLC-derived gp96 was administered together with 1 x 10(6) irradiated LLC/GM cells (p < 0.05). The antitumor effects of irradiated LLC/GM cells and LLC-derived gp96 required mainly CD8(+) T cells. Spleen cells obtained from mice vaccinated with irradiated LLC/GM cells and LLC-derived gp96 showed specific CD8 cytotoxic activities against LLC cells (specific lysis rate of approximately 28%). This antibody response was not associated with a synergic effect of the combination therapy. Moreover, draining lymph nodes from mice immunized with irradiated LLC/GM cells and LLC-derived gp96 contained more migrating mature CD11c(+) cells (higher levels of CD86 and major histocompatibility complex [MHC] class II molecules) compared with those from any other immunization protocols. These results suggest that the combination of irradiated LLC/GM cells and tumor-derived gp96 has potential as a new immunogene therapeutic strategy against lung cancer.

Animals↗
PubMed2003

CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers.

We investigated intratumoral tumor-infiltrating lymphocytes (TILs), including CD4(+) and CD8(+) T cells, in non-small cell lung cancers (NSCLCs) and their relationships with clinicopathological variables and post-operative survival. Tumor specimens from 178 NSCLCs were consecutively obtained by surgery at the Hokkaido University Medical Hospital between 1976 and 1994. CD8(+) T cells, CD4(+) T cells and Ki-67/CD8(+) T cells were visualized immunohistochemically, and counted within cancer cell nests and in cancer stroma. CD8(+) T cells and CD4(+) T cells were observed at higher frequencies within cancer cell nests in moderately and poorly differentiated tumors compared with well differentiated tumors (P < 0.01), and in tumors with high Ki-67 expression compared with low Ki-67 expression (P < 0.01), that showed severe cellular atypia and a higher growth rate. Patients with higher numbers of CD8(+) T cells within cancer cell nests showed significantly shorter survival times compared to those with lower numbers of CD8(+) T cells within cancer cell nests (5-year survival rates, 47% and 60%, respectively; P = 0.03). Moreover, patients with higher labeling index of Ki-67/CD8(+) T cells showed significantly shorter survival than those with lower labeling index of Ki-67/CD8(+) T cells within cancer cell nests (5-year survival rates, 41% and 69%, respectively; P = 0.02), and the labeling index of Ki-67/CD8(+) T cells within cancer cell nests was found to be a significant and independent unfavorable prognostic factor by multivariate analysis (P = 0.01). On the other hand, higher numbers of CD4(+) T cells in cancer stroma, but not within cancer cell nests, were correlated with longer survival times in patients with NSCLC (5-year survival rates, 64% and 43%, respectively; P = 0.04). CD4(+) T cells in cancer stroma might reflect immune responses against cancer cells, while CD8(+) T cells do not appear to work as effectors in tumor tissues of NSCLC. Moreover, the higher labeling index of Ki-67/CD8(+) T cells within cancer cell nests is a strong indicator of unfavorable clinical outcome.

Adenocarcinoma↗
PubMed2003

Predictive value of expression of P53, Bcl-2 and lung resistance-related protein for response to chemotherapy in non-small cell lung cancers.

Chemoresistance is a major problem in the chemotherapy of non-small cell lung cancers (NSCLCs). Several mechanisms are thought to be involved in drug resistance, including those associated with apoptosis, drug transport and detoxification. Here, we investigated the predictive value of P53, Bcl-2 and lung resistance-related protein (LRP) expression for response to platinum-based chemotherapy, using transbronchial biopsy (TBB) specimens from patients with NSCLC. We evaluated TBB specimens from 57 patients with NSCLC who had not previously been treated with either chemotherapy or radiotherapy before TBB, and who were treated with systemic platinum-based chemotherapy. The specimens included 33 adenocarcinomas, 22 squamous cell carcinomas and two large cell carcinomas. One to 6 courses of chemotherapy were administered. Expression of P53, Bcl-2 and LRP was analyzed by immunohistochemistry using TBB specimens. Positive expression of P53, Bcl-2 and LRP was observed in 28 (49%), 41 (71%) and 42 (73%) of the 57 NSCLCs, respectively. P53 expression correlated significantly with response to chemotherapy in nonsquamous cell carcinomas, including adenocarcinomas and large cell carcinomas (response rates, 38% and 6% for patients with P53-positive and P53-negative tumors, respectively, P = 0.03). LRP expression significantly correlated inversely with response to chemotherapy in squamous cell carcinomas (response rates, 33% and 100% for patients with LRP-positive and LRP-negative tumors, respectively, P = 0.02). Bcl-2 expression did not correlate with response to chemotherapy. These findings indicate that immunostaining for P53 and LRP using TBB specimens may be useful for dividing patients with NSCLC into chemoresponsive and chemoresistant groups.

Adenocarcinoma↗
PubMed2002

Real-time tumor-tracking radiation therapy for lung carcinoma by the aid of insertion of a gold marker using bronchofiberscopy.

BACKGROUND: The authors developed fluoroscopic real-time tumor-tracking radiation therapy (RTRT) by insertion of a gold marker using bronchofiberscopy to reduce uncertainties in organ motion and set-up error in external radiotherapy for moving tumors. The purpose of the current study was to evaluate RTRT's feasibility in lung carcinoma treatment. METHODS: The three-dimensional position of a 1.0-2.0 mm gold marker in or near the tumor was detected by two sets of fluoroscopies every 0.03 seconds. The treatment beam was gated to irradiate the tumor only when the position of the marker coincided with its planned position using the RTRT system. Bronchofiberscopic equipment for insertion of the marker into the lung tumor was developed and used for 20 lung tumors in 18 patients. Patients were given high dose hypofractionated focal irradiation (35-48 Gy in 4-8 fractions in 4-10 days) with a planning target volume margin of 5 mm for the tumor. RESULTS: The markers were successfully inserted and maintained at the inserted position during and after the radiotherapy in 14 (88%) of 16 peripheral-type lung tumors and in none of four central-type lung tumors, indicating that this method of RTRT was not feasible for central-type lung tumors. Tracking of the marker was successfully performed in 1 of 2 tumors with a 1.0 mm marker and in all of 12 tumors with a 1.5-2.0 mm marker. On the whole, 13 (65%) of the 20 tumors were successfully treated with RTRT. Local tumor control was achieved and maintained for all 12 patients (13 tumors), who were treated with RTRT, with a median followup of 9 months (range, 5-15). Localized radiation pneumonitis was found radiographically at the lung volume that was irradiated with about 20 Gy, without symptoms in all but one patient. CONCLUSIONS: The insertion of a gold marker into or near peripheral-type lung tumors using bronchofiberscopy is a feasible and safe technique. Excellent initial response and low incidence of clinical complications suggest that the high dose hypofractionated focal irradiation using the RTRT system can be a good local treatment for peripheral-type lung tumors.

Adult↗
PubMed2002

Small-volume image-guided radiotherapy using hypofractionated, coplanar, and noncoplanar multiple fields for patients with inoperable Stage I nonsmall cell lung carcinomas.

BACKGROUND: Occasionally, medically compromised and/or elderly patients with nonsmall cell lung carcinomas (NSCLCs) cannot be treated surgically. We investigated small-volume hypofractionated image-guided radiotherapy (IGRT) without the need for breath control in patients with inoperable Stage I NSCLCs. METHODS: Between September 1996 and September 1999, 22 patients with Stage I NSCLCs, including 19 males and 3 females, were treated with IGRT. Among these patients, there were 13 Stage IA and 9 Stage IB tumors. The tumors ranged in size from 14.2 to 58.5 mm, with a median size of 26.7 mm. Of the 22 patients, 19 were unfit for surgical treatment due to poor pulmonary function, complications, and/or advanced age and 3 refused surgery. Computed tomographic scans (CT) of the primary tumor were taken during three respiratory phases and they were analyzed to determine the planning target volume, which included only the primary tumor with allowances for respiratory movement. The radiation doses administered at the edge of the moving tumor during normal breathing were 80% of the prescribed dose, either 48 or 60 Gy given in eight fractions over 2 weeks. Clinical evaluation, chest CT scan, and pulmonary function tests were performed before irradiation and at regular intervals for the post-IGRT follow-up. The median follow-up period was 24 months (range, 2-44 months; mean, 21.8 months) (at least 24 months for survivors). RESULTS: Of 17 tumors assessed at the initial follow-up 2-6 months after treatment (5 complete responses, 11 partial responses, and 1 progressive disease), 16 (94%) were controlled locally. One local recurrence was observed during the follow-up. The lung carcinoma-specific survival rate at 1 year was 94% and the 1-year actuarial recurrence-free survival rate was 71%. The lung carcinoma-specific survival rate at 2 years was 73% and the 2-year actuarial recurrence-free survival rate was 67%. The treatment was well tolerated and no major side effects were observed. Localized radiation pneumonitis was observed in all patients who were examined by CT scan, but the patients were asymptomatic. Parameters of pulmonary function, including vital capacity, total lung capacity, and diffusion capacity for carbon monoxide, decreased very little or not at all, indicating that IGRT rarely deteriorated pulmonary functions. CONCLUSIONS: Small-volume hypofractionated IGRT without breath control is a feasible and beneficial method for the curative treatment of patients with Stage I NSCLCs. It has the potential of a high local tumor control rate and low morbidity.

Aged↗
PubMed2002

Increased expression of beta-catenin predicts better prognosis in nonsmall cell lung carcinomas.

BACKGROUND: beta-Catenin has been shown to function as a Wnt signaling molecule to stimulate cyclin D1 expression and cell growth in several kinds of tumors. METHODS: The authors immunohistochemically examined specimens of 217 surgically resected primary nonsmall cell lung carcinomas (NSCLCs) for beta-catenin expression and classified them semiquantitatively into three categories, including those with high, moderate, and low scores of expression. RESULTS: High, moderate, and low scores of expression were found in 37 (17.1%), 145 (66.8%), and 35 (16.1%) tumors, respectively. beta-Catenin expression was not correlated with cyclin D1 expression, but was positively correlated with the Ki-67 cell growth fraction (P = 0.04). The direct sequencing analysis for the beta-catenin gene mutation of 13 specimens of 217 tumors for the current study revealed no mutations. The relation between survival and beta-catenin expression was evaluated in 148 potentially curatively resected tumors with pathologic Stages I-IIIA. A trend toward better survival was found in patients with tumors having higher scores. In multivariate analysis, high beta-catenin expression was a significant and independent favorable prognostic factor (hazards ratio, 0.31; P = 0.007) as was pathologic stage. Analyzed by cell type, in nonsquamous cell carcinomas, patients with tumors having high scores survived a significantly longer time than those with tumors having moderate or low scores (5-year survival rates, 84%, 55%, and 32%, respectively; P = 0.02), and high beta-catenin expression tended to be a favorable prognostic factor (hazards ratio, 0.32; P = 0.052). CONCLUSIONS: These results indicate that, in NSCLCs, increased expression of beta-catenin can predict favorable prognosis of patients with resected tumors, suggesting that accumulation of beta-catenin has no or little oncogenic effect via activation of the Wnt pathway, unlike in colon carcinomas or hepatomas.

Aged↗
PubMed2002

RCAS1 expression: a potential prognostic marker for adenocarcinomas of the lung.

OBJECTIVE: RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a new tumor-associated antigen recognized by 22-1-1 monoclonal antibody. RCAS1 expressed on human cancer cells acts as a ligand for a putative receptor present on peripheral lymphocytes. RCAS1 has been shown to inhibit the in vitro growth of receptor-expressing cells and to induce apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we evaluated the prognostic significance of RCAS1 expression in primary lung adenocarcinomas. METHODS: Immunohistochemical analysis was performed on tissue specimens surgically obtained from 102 patients with primary lung adenocarcinomas. Then, the association of RCAS1 expression with clinicopathological variables and prognosis of patients were analyzed. RESULTS: Of 102 lung adenocarcinomas, positive RCAS1 expression was observed in 82 cases (80%). There was no correlation between RCAS1 expression and clinicopathological variables. In 70 potentially curatively resected lung adenocarcinomas, patients with RCAS1-positive tumors had a significantly shorter survival than those with RCAS1-negative tumors (p = 0.02), and RCAS1 expression was a significant and independent prognostic factor by multivariate analysis (p = 0.03). CONCLUSIONS: These results indicate that RCAS1 expression predicts prognosis in patients with lung adenocarcinomas, and this new antigen could be a novel tumor marker which reflects the clinical outcome of lung cancers.

Adenocarcinoma↗
PubMedDate not supplied

Inverted papilloma of the nasal cavity presenting with massive amounts of squamous metaplastic cells in sputum. A case report.

BACKGROUND: Squamous metaplasic cells are rarely seen in sputum of female nonsmokers. CASE: A 47-year-old female nonsmoker presented with massive amounts of squamous metaplasic cells in sputum and an elevated level of squamous cell carcinoma (SCC) antigen in serum present for months, while no causative lesion was detected either by lung computed tomography or bronchoscopy. The patient was eventually diagnosed as having inverted papilloma in the right nasal cavity. Resection of the tumor brought about disappearance of squamous metaplastic cells in sputum and return of serum SCC antigen to the normal range. CONCLUSION: This case clearly demonstrates that squamous metaplastic cells in sputum can originate in lesions in the nasal cavity, although they are rare. It should be kept in mind that the nasal cavity is a potential site producing squamous metaplastic cells in sputum.

Antigens, Neoplasm↗
PubMedDate not supplied

Topoisomerase inhibitor-induced apoptosis accompanied by down-regulation of Bcl-2 in human lung cancer cells.

BACKGROUND: Anticancer drug-induced apoptosis is one of the important mechanisms in the effectiveness of chemotherapy. In this study, we investigated apoptosis induced by topoisomerase inhibitors and its relationship with chemosensitivity, the expression of Bcl-2 family proteins and p53 status in human lung cancer cells. MATERIALS AND METHODS: A total of six human lung cancer cell lines, i.e., two small cell lung cancer (SCLC) and four non-small cell lung cancer (NSCLC) cell lines, were used. For induction of apoptosis, these cell lines were treated with SN-38 (DNA topoisomerase I inhibitor) or etoposide (DNA topoisomerase II inhibitor). Drug sensitivity was determined using a microculture tetrazolium assay. The rates of apoptosis and alterations of Bcl-2 and Bax expression were analyzed by flow cytometry. RESULTS: Apoptotic cells increased in a time-dependent manner after exposure to topoisomerase inhibitors. Induction of apoptosis was accompanied by the down-regulation of Bcl-2 expression, but there was little alteration of Bax expression. These events were significantly more extensive in SCLC cell lines, which are more sensitive to topoisomerase inhibitors, than in NSCLC cell lines, which are more resistant to these inhibitors. However, neither induction of apoptosis nor chemosensitivity correlated with p53 status in the lung cancer cell lines studied. CONCLUSION: The more extensive induction of apoptosis with Bcl-2 down-regulation in SCLC than in NSCLC might explain, at least in part, the higher clinical sensitivity to topoisomerase inhibitors in the former disease.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Analysis of the response and toxicity to gefitinib of non-small cell lung cancer.

BACKGROUND: Gefitinib is an oral agent that inhibits the tyrosine kinase of epidermal growth factor receptor (EGFR), which had antitumor activity in patients with previously treated non-small cell lung cancer (NSCLC). We analyzed the efficacy, toxicity and overall survival time of gefitinib treatment in patients with NSCLC. PATIENTS AND METHODS: One hundred and twenty-two patients with NSCLC, who received gefitinib between 2002 and 2004 in our institutes, were evaluated retrospectively. RESULTS: The objective response rate was 24.6%. The variables identified as significant in univariate analysis included gender and smoking habit. The median overall survival time was 14.4 months. Significant variables associated with improved survival included good performance status (PS), female, adenocarcinoma and never smoked status, while never smoked status and good PS were independent prognostic factors in multivariate analysis. Four patients (3.3%) developed interstitial pneumonitis associated with gefitinib. CONCLUSION: Gefitinib showed favorable anti-tumor activity in females, never smokers and adenocarcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Phase II study of carboplatin and weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: The optimal schedule of taxane administration has been an area of active interest in several clinical trials. PATIENTS AND METHODS: To evaluate the efficacy and toxicity of carboplatin and weekly paclitaxel combination chemotherapy, a phase II study was conducted for chemo-naïve, advanced non-small cell lung cancer (NSCLC) patients. Patients received paclitaxel 100 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of area under the curve of 6 on day 1 every 28 days. RESULTS: Forty patients were enrolled. Overall response rate and survival at one year by intent-to-treat analyses was 35% and 57.5%, respectively. The median survival time was 12.2 months. Twenty-two patients (56%) had grade 3 or greater neutropenia. Grade 3 sensory and motor neuropathy were seen in one patient (3%). CONCLUSION: Carboplatin and weekly paclitaxel combination chemotherapy is an active and feasible regimen for patients with advanced NSCLC.

Adult↗