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Biomedical subjects

Mitsunori Ohta

Publications and source records attributed to Mitsunori Ohta.

At least 19 recordsLinked to original sources
PubMed2007

Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to world health organization histologic classification system.

BACKGROUND AND OBJECTIVES: The aim of this study was to clarify the significance of surgical treatment for recurrent thymic epithelial tumors with reference to the World Health Organization (WHO) histological classification system. PATIENTS: Among 67 patients with tumor recurrence, 22 underwent a re-resection. There were 1 patient with a type AB tumor, 5 with type B1 tumors, 10 with type B2 tumors, 5 with type B3 tumors, and 1 with a carcinoma. RESULTS: The 10-year survival rate following the initial resection was 70% in patients who underwent a re-resection and 35% in those who did not. The average intervals from the initial resection to re-resection were 10.3, 7.8, 6.0, 2.4, and 2.6 years for patients with type AB, B1, B2, B3 tumors, and carcinoma, respectively. The patient with a type AB tumor was alive at 2.4 years after re-resection, 12.7 years after the initial resection. The 5-year survival rates following re-resection in the patients with type B1, B2, and B3 tumors were 100, 56, and 60, respectively. The patient with a carcinoma died as a result of the tumor 2 years after re-resection. CONCLUSION: WHO histological classification indicates the outcome of surgical treatment for recurrent thymic epithelial tumors.

Adult↗
PubMed2006

Results of pulmonary resection following neoadjuvant therapy for locally advanced (IIIA-IIIB) lung cancer.

OBJECTIVE: We performed this study to determine the role and prognostic factors of neoadjuvant therapy followed by surgery for locally advanced non-small cell cancer. METHODS: One hundred patients with clinical stage III non-small cell lung cancer (79 IIIA, 21 IIIB; 78 males, 22 females; average age 60.5 years) received neoadjuvant therapy, of whom 84 received two cycles of platinum chemotherapy combined with an average radiation dose of 41.5Gy, and 16 patients underwent chemotherapy alone. The mean follow-up duration was 80.9 months. Survival rate was estimated by the Kaplan-Meier method, and a Cox proportional hazards model was applied to determine the prognostic factors. RESULTS: The operative procedures included 74 lobectomies, 7 bi-lobectomies, and 19 pneumonectomies. Two patients died within 30 days due to adult respiratory distress syndrome and acute pulmonary embolism, respectively. The overall 5-year survival rate was 39.7% with a median survival time (MST) of 39.6 months. The 5-year survival rate for downstaged (pN1,2) patients was 53.5% while it was 16.3% for patients with residual N2. There was no difference in survival between lobectomy and pneumonectomy (MST 38 months vs 42 months). Univariate and multivariate analyses revealed that nodal status and tumor size after neoadjuvant therapy were independent prognostic factors. CONCLUSIONS: Neoadjuvant therapy was shown to deliver the optimal effect for surgery for cIIIA/IIIB NSCLC with acceptable mortality. Re-staging to exclude the residual multiple nodal metastasis can lead to the proper patient selection. A pneumonectomy, as a last option, following neoadjuvant therapy did not affect the mortality.

Aged↗
PubMed2006

Detection of occult tumor cells in lymph nodes from non-small cell lung cancer patients using reverse transcription-polymerase chain reaction for carcinoembryonic antigen mRNA with the evaluation of its sensitivity.

We evaluated the usefulness of a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for detecting occult tumor cells in histologically malignant-negative lymph nodes resected from patients with non-small cell lung cancer. First, we examined the relationship between tumor cell number and carcinoembryonic antigen (CEA) mRNA copy number using a PCR method with a cancer cell line (A549) in a serial dilution study. Next, we evaluated the relationship between nodal metastatic area size and CEA mRNA copy number using lymph nodes with histologically proven metastasis in a serial slice study. On the basis of those results, we performed RT-PCR analyses with 28 primary tumors and 211 lymph nodes from 28 patients who underwent a lobectomy with systematic node dissection. Our results in the serial dilution study showed that the detectable limitation by quantitative RT-PCR was 25-100 neoplastic cells and 20-100 CEA mRNA copy numbers. In the serial slice study, we found a correlation between CEA mRNA copy number and nodal metastatic area. In the clinical samples, amplification of CEA mRNA was obtained with all 28 primary tumors and 13 of the lymph nodes with metastasis shown by hematoxylin-eosin staining. Furthermore, 52 (25%) of 211 histologically negative lymph nodes and the specimens from 14 (64%) of the 22 pN0 patients revealed a significant level of CEA mRNA. These results indicate that micrometastases, which are not detectable with conventional examinations, can be detected by the present method of RT-PCR for CEA mRNA in a proportion of patients with resected pN0 non-small cell lung cancer.

Adult↗
PubMed2006

Comparison of surgical results after pneumonectomy and sleeve lobectomy for non-small cell lung cancer: trends over time and 20-year institutional experience.

OBJECTIVE: Sleeve lobectomy is a lung-saving procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study was to report the clinical characteristics, operative results, survival, and late outcomes over 20 years in patients who underwent sleeve lobectomy and pneumonectomy at our institution. METHODS: There were 62 patients who underwent sleeve lobectomy (SL group) and 110 who underwent pneumonectomy (PN group). Comparisons of the demographics, morbidity, and survivals between the groups were performed by unpaired t-test, chi(2)-test, and log-rank test. RESULTS: Patients who underwent a pneumonectomy showed a significantly advanced pathological stage, and a larger tumor size than those who received a sleeve lobectomy, whereas there were no significant differences in histology, ratio of combined resection and induction therapy, or total morbidity. There were three in-hospital deaths (4.8%) in the SL group and four (3.6%) in the PN group. Local relapse and distant recurrence incidence were similar between the two groups. The 5-year-survival rates of the SL and PN groups were 54% and 33%, respectively (p<0.0001). However, there were no differences in 5-year survivals in patients with pathological stage I/II (SL, 59% vs PN, 63%) and those who received induction therapy (SL, 22% vs PN, 52%) between the groups. CONCLUSIONS: Both pneumonectomy and sleeve lobectomy were performed with an acceptable risk of operative mortality and satisfactory 5-year survival rate. The indication of pneumonectomy is aimed to perform a curative resection for locally advanced lung cancer, particularly after induction therapy that is otherwise unresectable, and the selected patients will likely benefit from a complete resection.

Aged↗
PubMed2006

Pulmonary artery dissection complicating lung transplantation for primary pulmonary hypertension.

We report a case of pulmonary artery (PA) dissection complicating lung transplantation. A 30-year-old man with primary pulmonary hypertension underwent bilateral single lung transplantation. Thirty hours postoperatively he had signs of obstruction of the right main pulmonary artery develop due to dissection demonstrated on transesophageal echocardiography and pulmonary arteriography. Surgical repair of the dissection with reanastomosis of the pulmonary artery was successfully carried out, and the patient subsequently improved to a favorable condition. Pulmonary hypertension is a risk factor of pulmonary artery dissection; our case suggested that underlying chronic pulmonary hypertension might have led to this rare and life-threatening anastomotic problem after lung transplantation.

Adult↗
PubMed2005

Role of positive selection of thymoma-associated T cells in the pathogenesis of myasthenia gravis.

BACKGROUND: A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alphabeta or gammadelta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. MATERIALS AND METHODS: Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. RESULTS: The average proportion of TCRalphabeta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCRalphabeta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCRalphabeta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas. CONCLUSIONS: The possible role of development of TCRalphabeta(+) T cells, especially the role of positive selection of TCRalphabeta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.

Adult↗
PubMed2005

Amelioration of pulmonary emphysema by in vivo gene transfection with hepatocyte growth factor in rats.

BACKGROUND: Hepatocyte growth factor (HGF) is an important mitogen and morphogen that contributes to the repair process after lung injury. The goal of the present study was to characterize its role in pulmonary emphysema, which may lead to the development of new treatment strategies with HGF. METHODS AND RESULTS: HGF mRNA and protein levels in lung tissue and plasma from elastase-induced emphysema rats transiently increased, then declined significantly to below the basal level in a time-dependent manner (P<0.01). Furthermore, changes in HGF were correlated with histologically progressive emphysematous changes and deterioration in pulmonary physiology. Use of the HVJ (hemagglutinating virus of Japan) envelope method resulted in successful transfection of cDNA encoding human HGF, as demonstrated by an efficient expression of HGF in alveolar endothelial and epithelial cells. Transfection of HGF resulted in a more extensive pulmonary vasculature and inhibition of alveolar wall cell apoptosis, and those effects led to improved exercise tolerance and gas exchange (P<0.05), which persisted for more than 1 month. CONCLUSIONS: Decreased HGF expression due to a failure in sustained endogenous production after injury was associated with emphysema-related histopathologic and physiological changes in the present rat model. In addition, induction of HGF expression by a gene-transfection method resulted in improved pulmonary function via inhibition of alveolar cell apoptosis, enhancement of alveolar regeneration, and promotion of angiogenesis.

Animals↗
PubMed2005

Glucocorticoids induce G1 cell cycle arrest in human neoplastic thymic epithelial cells.

PURPOSE: Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells. PATIENTS AND METHODS: Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis. RESULTS: GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n = 6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression. CONCLUSIONS: Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.

Adult↗
PubMed2005

False positive accumulation in 18F fluorodeoxyglucose positron emission tomography scan due to sarcoid reaction following induction chemotherapy for lung cancer.

We present a case of lung cancer that showed false positive accumulation in an 18F fluorodeoxyglucose positron emission tomography (FDG-PET) scan following induction chemotherapy for suspected metastasis and progression of malignancy. A 66-year-old man was diagnosed with squamous cell carcinoma in the lung, classified as clinical stage IIIA (T2N2M0), and underwent induction chemotherapy. An FDG-PET scan prior to chemotherapy demonstrated accumulation only in the tumor, whereas following treatment it revealed a strong accumulation not only in the tumor, but also in the supraclavicular lymph nodes, which indicated lymph node metastasis. The patient underwent a biopsy of the right supraclavicular lymph node and mediastinoscopy, after which all dissected lymph nodes showed sarcoid reactions and no tumor cells were found pathologically. We concluded that when evaluating the effect of induction chemotherapy for malignancy, a sarcoid reaction might lead to the false positive accumulation of FDG.

Aged↗
PubMed2005

Attenuation of lung injury in allograft rejection using NF-kappaB decoy transfection-novel strategy for use in lung transplantation.

OBJECTIVE: Increased production of nitric oxide (NO) is known to be a marker of lung allograft rejection and lung injury. NO production is up-regulated directly or indirectly by nuclear factor-kappa B (NF-kappaB), a transcriptional factor of inflammatory cytokines and iNOS. We attempted to determine whether transfection of an NF-kappaB decoy into allografts could reduce NO production and ameliorate acute lung injury during allograft rejection. METHODS: Left lung transplantation was performed in pairs of Brown Norway (RT1n) and Lewis (RT1) rats. In Group NF (n=6), the allografts were flushed with 20 ml of PBS solution containing a hemagglutinating virus of Japan (HVJ) liposome-ODN complex as an NF-kappaB decoy and preserved for 60 min at 4 degrees C. A scramble decoy was used in the positive control (Group S, n=5) and simple PBS solution in the negative control (Group C, n=5). Five days after transplantation without use of immuno-suppressants, exhaled NO, gas exchange, and graft histological rejection score were determined. RESULTS: The exhaled NO level was significantly reduced in Group NF as compared with Group S (445+/-162 vs 1305+/-123 ppb, P<0.02), while improvements in PaO2 (197+/-28 vs. 60+/-18 mmHg, P<0.02) and rejection score (1.8+/-0.3 vs. 2.5+/-0.4) were also observed. There were no differences in these parameters between Groups S and C. CONCLUSIONS: Inhibition of NF-kappaB activation in the allograft by ODN decoy transfection into the donor lung ameliorated lung injury during acute allograft rejection. Our results imply a possible therapeutic target for the inflammation process in lung transplantation clinical settings.

Acute Disease↗
PubMed2005

Application of HVJ-liposome mediated gene transfer in lung transplantation-distribution and transfection efficiency in the lung.

OBJECTIVE: A novel hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer system has been shown to have benefits of a high efficiency of transfection and low immunogenicity. The aims of this study were to determine the effect of re-transfection of the HVJ-liposome system via the airway, and to quantify the distribution of gene expression between transtracheal and transplantation approaches. METHODS: Beta-galactosidase (beta-gal) plasmid DNA was introduced into lung tissues using the HVJ-liposome method. Two groups of Sprague-Dawley (SD) rats received intratracheal instillation of 10 microg of the beta-gal gene, once on Day 0 in 1 group (Group Tb-1, n=4) and 3 times on Days 0-2 in another (Group Tb-3, n=4). In a third group of SD rats (Group Tx, n=5), an orthotopic left lung transplantation was performed after the donor lung was flushed with an HVJ-liposome complex solution and preserved for 1h. Gene expression and distribution in lung tissue was then quantified by counting the X-gal stained cells. RESULTS: Both the transtracheal and transplantation approaches resulted in low levels of transfection in the vascular endothelial cells (0.2+/-0.1 and 4.0+/-1.8%), respectively, but a moderate degree of transfection to the airway (11.0+/-7.1 and 28.0+/-20.7%) and alveolar cells (3.0+/-1.8 and 6.0+/-3.6%). Three repetitive injections via the airway increased gene expression in airway epithelial cells of 41.0+/-12.0% compared with the single administration of 11.0+/-4.3%. CONCLUSIONS: Our results suggest that the repeated transtracheal gene transfection using HVJ-liposome may have benefits for treatment of problems after lung transplantation. In addition, gene transfer using a flushing solution during harvest may provide an opportunity for gene manipulation in the setting of lung transplantation.

Animals↗
PubMed2005

Long-term graft patency after replacement of the brachiocephalic veins combined with resection of mediastinal tumors.

OBJECTIVE: We sought to investigate the correlation between type of vascular reconstruction and long-term graft patency after replacement of brachiocephalic veins combined with resection of mediastinal malignancies. METHODS: Eighteen patients underwent surgical resection of tumors and the superior vena cava with concomitant vascular reconstruction using ringed polytetrafluoroethylene grafts. Graft patency was verified by means of venography or contrast-enhanced computed tomography at time points ranging from 3 to 77 months (median, 33 months) postoperatively. RESULTS: Seven patients underwent sole reconstruction of the right brachiocephalic vein, with occlusion observed in only 1 patient. In 6 patients who underwent reconstruction of the bilateral brachiocephalic veins with 2 separate grafts, the grafts remained patent in 2, whereas 4 patients experienced occlusion of one of the two grafts yet remained asymptomatic. Both patients who underwent reconstruction with a Y graft experienced left brachiocephalic vein graft occlusion. In the 3 patients who underwent reconstruction of a left brachiocephalic vein, the graft became occluded, and superior vena cava syndrome developed in 2 of these patients. CONCLUSION: When replacing the superior vena cava, reconstruction of a left brachiocephalic vein alone results in a significant rate of occlusion and development of superior vena cava syndrome. Thus we advocate sole right brachiocephalic vein reconstruction or bilateral brachiocephalic vein reconstruction in this setting, and separate reconstruction of the veins is preferable to use of a Y graft.

Adolescent↗
PubMed2005

Surgical resection for lung cancer with infiltration of the thoracic aorta.

OBJECTIVE: The purpose of this study was to evaluate the results of a combined resection of the thoracic aorta and primary lung cancer. METHODS: Sixteen patients underwent thoracic aorta resection along with a left pneumonectomy (n = 6), left upper lobectomy (n = 9), or partial lung resection (n = 1), of whom 10 also received preoperative induction therapy. Cardiopulmonary bypass was used in 10 patients, and a passive shunt between the ascending aorta and the descending aorta was used in 4 patients. RESULTS: Six postoperative major complications occurred in 5 patients, including postoperative bleeding (n = 3), intraoperative bleeding (n = 1), chylothorax (n = 1), and respiratory failure (n = 1). The postoperative morbidity rate was 31%, and the mortality rate was 12.5% (2/16). Furthermore, 4 patients died of systemic tumor relapse, and 1 patient died of intrapleural recurrence. Nine patients were alive after a median follow-up of 54 months (range, 12-199 months). The median survival time of patients with postoperative pathologic N0 disease was 31 months, whereas it was 10 months for those with pathologic N2 or N3 disease. Five-year survivals were 70% for patients with N0 disease and 16.7% for patients with N2 or N3 disease ( P = .0070). CONCLUSIONS: Although pulmonary resection with the involved aorta might cause high surgical morbidity and mortality rates, encouraging long-term survivals were obtained in patients without mediastinal nodal involvement.

Adenocarcinoma↗
PubMed2004

Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis.

The "a disintegrin and metalloprotease" (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9, -10, -12, -15, and -17 in sublines of an EBC-1 lung cancer cell line that were highly metastatic to either brain or bone. ADAM9 mRNA levels were significantly higher in highly brain-metastatic sublines than in the parent or highly bone-metastatic sublines. To elucidate the role of ADAM9 in brain metastasis, we stably transfected A549 and EBC-1 cells with a full-length ADAM9 expression vector. Compared with mock-transfectants, ADAM9 overexpression resulted in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha 3 and beta 1 subunits. Administration of the anti-beta 1 monoclonal antibody attenuated this increase in invasive and adhesive activity. Intravenous administration of ADAM9-overexpressing A549 cells to mice resulted in micrometastatic foci in the brain and multiple metastatic colonies in the lungs. In contrast, administration of parent and mock-transfected A549 cells to mice resulted in lung tumors without brain metastasis. These results suggest that ADAM9 overexpression enhances cell adhesion and invasion of non-small cell lung cancer cells via modulation of other adhesion molecules and changes in sensitivity to growth factors, thereby promoting metastatic capacity to the brain.

ADAM Proteins↗
PubMed2004

Living-related lobar transplantation and simultaneous atrial septal defect closure in a young patient with irreversible pulmonary hypertension: a case report.

A 6-year-old boy was diagnosed as having atrial septal defect with oversystemic pulmonary hypertension, and gradually developed hypoxia and heart failure. At the age of 11, living-related bilateral lobar lung transplantation from his parents was indicated, because of his critical condition. The estimated forced vital capacity calculated by the donors' lower lobes was 104% of his age. The operation was carried out with simultaneous closure of the atrial septal defect under full cardiopulmonary bypass. The postoperative course was complicated with pulmonary edema and phrenic nerve palsy, which were eventually resolved. Six months after surgery he was free from heart failure and rehabilitating at home without oxygen. The final diagnosis was primary pulmonary hypertension with atrial septal defect. Living-related bilateral lobar lung transplantation with simultaneous intracardiac repair may be an optional strategy for children with Eisenmenger syndrome or primary pulmonary hypertension with intracardiac defect when cadaveric transplantation is not possible.

Cardiopulmonary Bypass↗
PubMed2004

Benefits of home parenteral nutrition before lung transplantation: report of a case.

A 54-year-old woman, who was severely malnourished and awaiting lung transplantation for chronic respiratory failure, was given nutritional support by home parenteral nutrition (HPN). The patient's emaciated state was further compromised by the fact that she had undergone a distal gastrectomy 4 years earlier. We decided that HPN was indicated because her oral intake was so poor and drinking enteral formula reduced her appetite. After 1 year of HPN, her body weight increased and her nutritional, anthropometric, and biochemical values were well maintained by the time of transplantation. Moreover, her progress after lung transplantation was remarkably good, indicating the effectiveness of nutritional support by HPN during the protracted waiting period.

Chronic Disease↗
PubMed2004

Induction concurrent chemoradiation therapy for invading apical non-small cell lung cancer.

OBJECTIVE: Although non-small cell lung cancer (NSCLC) involving the superior sulcus has been generally treated with radiation therapy (RT) followed by surgery, local recurrence is still a big problem to be solved. We investigated a role of induction therapy, especially induction concurrent chemoradiation therapy (CRT), on the surgical results of this type of NSCLC. METHOD: We retrospectively reviewed 30 patients with NSCLC invading the apex of the chest wall who underwent surgery from 1987 to 1996. Ten patients (57 +/- 8 years) received surgery alone, 9 (55 +/- 13 years) received RT (42 +/- 7 Gy) followed by surgery and 11 (51 +/- 9 years) received cisplatin based chemotherapy and RT (47 +/- 5 Gy) as an induction therapy. RESULTS: Two and 4-year survival rates were 30% and 20% in patients with surgery alone, 22% and 11% in patients with induction RT, and 73% and 53% in patients with induction CRT, respectively. The survival was significantly better in patients with induction CRT than those with induction RT or surgery alone. Univariate analysis demonstrated that curability (yes versus no: p = 0.027) and induction therapy (surgery alone and RT versus CRT: p = 0.0173) were significant prognostic factors. Multivariate analysis revealed that only induction therapy (p = 0.0238) was a significant prognostic factor. CONCLUSIONS: Induction CRT seems to improve the survival in patients with NSCLC invading the apex of the chest wall compared with induction RT or surgery alone.

Antineoplastic Combined Chemotherapy Protocols↗