Significant correlation between endothelial nitric oxide synthase (eNOS) expression and alveolar repair in elastase-induced rat pulmonary emphysema.

BACKGROUND AND PURPOSE: Angiogenic factors, such as endothelial nitric oxide synthase (eNOS), are thought to play an important role in the repair of pulmonary emphysema (PE); yet, the correlation of the factors involved has not been investigated. We conducted this study to clarify the positive correlation between eNOS expression and alveolar repair in PE recovery. METHODS: We used elastase to induce PE in rats, which were divided into Groups A (Control), B (G-CSF), C (PE) and D (PE + G-CSF). G-CSF was injected for 12 days, 4 weeks after which the alveolar walls, arterioles, and angiogenic factors including eNOS were examined histopathologically and by western blotting. RESULTS: In comparing Groups A, B, C, and D, the alveolar density was 2.4 ± 0.2, 2.4 ± 0.1, 1.8 ± 0.1, 2.5 ± 0.1 per 100 µm(2), respectively (C vs. others; p < 0.00001) and the number of arterioles was 4.5 ± 1.0, 5.6 ± 0.6, 3.2 ± 0.5, 5.5 ± 0.7/mm(2), respectively (C vs. others; p < 0.05). Immunohistochemical staining (IHC) revealed different eNOS expression in Group D versus Group C (p < 0.0001) and western blotting revealed different eNOS, VEGF, and FLT-1 expression in Group D versus Group C (p < 0.01, p < 0.05, p < 0.001), reflecting the contribution of angiogenesis to PE repair. eNOS showed a significantly positive correlation to alveolar density and arteriole repair. CONCLUSION: Alveolar repair was correlated positively with eNOS expression by vascular regeneration in elastase-induced rat PE.

Expression of a splicing variant of the CADM1 specific to small cell lung cancer.

CADM1, a member of the immunoglobulin superfamily cell adhesion molecule, acts as a tumor suppressor in a variety of human cancers. CADM1 is also ectopically expressed in adult T-cell leukemia (ATL), conferring an invasive phenotype characteristic to ATL. Therefore, CADM1 plays dual roles in human oncogenesis. Here, we investigate the roles of CADM1 in small cell lung cancer (SCLC). Immunohistochemistry demonstrates that 10 of 35 (29%) primary SCLC tumors express CADM1 protein. Western blotting and RT-PCR analyses reveal that CADM1 is significantly expressed in 11 of 14 SCLC cells growing in suspension cultures but in neither of 2 SCLC cells showing attached growth to plastic dishes, suggesting that CADM1 is involved in anchorage-independent growth in SCLC. In the present study, we demonstrate that SCLC expresses a unique splicing variant of CADM1 (variant 8/9) containing additional extracellular fragments corresponding to exon 9 in addition to variant 8, a common isoform in epithelia. Variant 8/9 of CADM1 is almost exclusively observed in SCLC and testis, although this variant protein localizes along the membrane and shows similar cell aggregation activity to variant 8. Interestingly, both variant 8/9 and variant 8 of CADM1 show enhanced tumorigenicity in nude mice when transfected into SBC5, a SCLC cell lacking CADM1. Inversely, suppression of CADM1 expression by shRNA reduced spheroid-like cell aggregation of NCI-H69, an SCLC cell expressing a high amount of CADM1. These findings suggest that CADM1 enhances the malignant features of SCLC, as is observed in ATL, and could provide a molecular marker specific to SCLC.

Postoperative follow-up for patients with non-small cell lung cancer.

BACKGROUND: It is unclear whether postoperative follow-up by thoracic surgeons or chest physicians for non-small cell lung cancer (NSCLC) alters survival. PATIENTS AND METHODS: The charts of 1,398 NSCLC patients, diagnosed between 1980 and 2008, were reviewed. Prognostic factors contained therein were evaluated using univariate and multivariate analyses. Patients were divided into 2 groups according to the doctor in charge of their postoperative follow-up: the thoracic surgeon group and the chest physician group. The doctors in charge of following up the patients were also analyzed for prognostic significance. RESULTS: In the univariate and multivariate analyses, age 65 years or younger, female sex, early pathological stage, Charlson Index score of 0-1, absence of adjuvant therapy, and follow-up by a chest physician were significantly favorable prognostic factors. Examined overall, NSCLC patients in the chest physician group had longer survival than those in the thoracic surgeon group. The difference in survival of patients with advanced disease was also statistically significant between these 2 groups. CONCLUSIONS: Our results indicate that early detection of asymptomatic disease by regular follow-up including chest computed tomography scan may improve the chance of treatment with curative intent and thus may increase survival, irrespective of the doctor in charge of follow-up.

Blood flow velocity is reduced in a tumor micro-dissemination in the visceral pleura in anesthetized open-chest rat lung.

BACKGROUND: Recently we developed a method to observe pulmonary micrometastasis by labeling cancer cells with green fluorescent protein (GFP). We applied the method for observation of micro-dissemination on the visceral pleura. MATERIALS AND METHODS: RCN9 rat colon cancer cells labeled with GFP were injected into the pleural cavity of Fischer F344 rats. Six weeks after injection, the chest wall was resected under general anesthesia and the lung surface was observed by real-time confocal laser-scanning microscopy. Blood flow was visualized by intravenous injection of fluorescein isothiocyanate-labeled red blood cells, by which blood flow velocity was measured. RESULTS: Dissemination was created in 4 out of 5 rats. Fifteen sites of micro-dissemination were observed (mean diameter, 35.8+/-13.3 microm). Blood flow velocity was 114.1+/-26.1 microm/s in the tumor tissue and 183.4+/-35.0 microm/s out of the tumor tissue. CONCLUSION: We were able to observe pleural micro-dissemination. Blood flow velocity was significantly lower in the tumor tissue.

Preoperative CYFRA 21-1 levels as a prognostic factor in c-stage I non-small cell lung cancer.

OBJECTIVE: The clinical importance of preoperative CYFRA 21-1 measurement in early-stage non-small cell lung cancer (NSCLC) is still unclear. The aim of this study is to clarify the prognostic value of preoperative CYFRA 21-1 levels in clinical stage (c-stage) I NSCLC. METHODS: The records of 101 c-stage I NSCLC patients who had undergone complete resection were analyzed to correlate preoperative CYFRA 21-1 levels to both the pathologic factors of resected specimens and postoperative outcomes. The cut-off value was set at 3.5 ng/ml. RESULTS: Six cases (5.9%) showed high CYFRA 21-1 (> or =3.5 ng/ml). The 5-year survival of normal and high CYFRA 21-1 groups was 83.3% and 50.0%, respectively. Patients with high CYFRA 21-1 had significantly poor outcomes (P=0.006). In univariate analysis, preoperative serum CYFRA 21-1 level, pT, pN, and p-stage were significantly associated with prognosis. Multivariate analysis showed that only CYFRA 21-1 level was retained as an independent prognostic factor (relative risk=9.79, P=0.002). CONCLUSIONS: CYFRA 21-1 is an independent predictor of poor outcome for c-stage I NSCLC. Elevated preoperative CYFRA 21-1 levels in early-stage NSCLC may indicate a subgroup at high risk of early death, which has the potential for better survival with additional systemic chemotherapy.

Promoter methylation of DAL-1/4.1B predicts poor prognosis in non-small cell lung cancer.

PURPOSE: DAL-1/4.1B is an actin-binding protein originally identified as a molecule whose expression is down-regulated in lung adenocarcinoma. We have previously shown that a lung tumor suppressor, TSLC1, associates with DAL-1, suggesting that both proteins act in the same cascade. The purpose of this study is to understand the molecular mechanisms and clinical significance of DAL-1 inactivation in lung cancer. EXPERIMENTAL DESIGN: We studied aberration of the DAL-1 in 103 primary non-small cell lung cancers (NSCLC) and 18 lung cancer cells. Expression and allelic and methylation status of DAL-1 was examined by reverse transcription-PCR, microsatellite analysis, and bisulfite sequencing or bisulfite single-strand conformational polymorphism, respectively. RESULTS: Loss of DAL-1 expression was strongly correlated with promoter methylation in lung cancer cells, whereas DAL-1 expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine. The DAL-1 promoter was methylated in 59 (57%) primary NSCLC tumors, 37% of which were associated with loss of heterozygosity around the DAL-1 on chromosomal region 18p11.3. In squamous cell carcinomas, DAL-1 methylation was observed in 9 of 10 tumors at stage I, whereas the incidence of methylation gradually increased in adenocarcinomas as they progressed [13 of 36 (36%), 4 of 12 (33%), 14 of 17 (82%), and 3 of 3 (100%) tumors at stages I, II, III, and IV, respectively; P = 0.0026]. Furthermore, in adenocarcinomas, disease-free survival and overall survival were significantly shorter in patients with tumors harboring the methylated DAL-1 (P = 0.0011 and P = 0.045, respectively). CONCLUSIONS: DAL-1 methylation is involved in the development and progression of NSCLC and provides an indicator for poor prognosis.

Prognostication of small-sized primary pulmonary adenocarcinomas by histopathological and karyometric analysis.

To reveal useful prognostic factors in cases of small-sized pulmonary adenocarcinoma, we conducted a histological and karyometric analysis of 116 small-sized pulmonary adenocarcinomas measuring less than 2 cm in maximum diameter and four specimens of atypical adenomatous hyperplasia (AAH). The small-sized pulmonary adenocarcinomas were classified by using criteria described previously [Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Lung Cancer 1995:75;2844-52]. There were 99 tumors of replacement-type adenocarcinoma, comprising 11 type A, localized bronchioloalveolar adenocarcinoma (LBAC); 6 type B, LBAC with alveolar collapse; and 82 type C, LBAC with foci of fibroblastic proliferation. The 17 remaining tumors were non-replacement-type adenocarcinomas. Among the potential prognostic factors examined, histological subtype was the most closely correlated with 5-year relapse-free survival rate. Furthermore, in patients with type C adenocarcinomas, a small fibroblastic proliferation (F) to fibrosis area (f) ratio (F-f ratio) (<10%) of the tumor and a small maximum nuclear diameter (Max ND; <13.50 microm) of tumor cells were closely associated with an excellent prognosis. Histological subtypes of type A and B adenocarcinomas, a small F-f ratio, and a small Max ND of type C adenocarcinomas were closely correlated with an excellent prognosis in small-sized adenocarcinoma.

Diffuse pulmonary hamartoma: a case report.

Pulmonary hamartoma usually occurs as a benign, well-circumscribed single nodule in the lung parenchyma. We report on a unique case of hamartoma that extended along the bronchial tree, formed endobronchial polypoid lesions, and expanded into the lung parenchyma. The patient, a 48-year-old man, was admitted with dyspnea and chest pain. A transbronchial biopsy was performed on a tumorous lesion that was diagnosed histologically as a hamartoma. As this lesion was found to be growing diffusely along the bronchial tree, a left pneumonectomy was performed. Gross examination showed that yellowish soft tissue had surrounded the bronchial tree and extended into the lung parenchyma. Histologically, the lesion contained mainly mature adipose tissue, cartilage, and muscle tissue with a minor component of short spindle cells in a myxomatous matrix. The patient was diagnosed as having diffuse pulmonary hamartoma.

Primary chondrosarcoma of the lung recognized as a long-standing solitary nodule prior to resection.

As the use of computed tomography (CT) increases, incidental lung nodules have become a clinical issue that is being addressed more than before. We detected a solitary lung nodule which was smooth-margined, round-shaped, 11 mm in size. Follow-up for 18 months after initial detection by chest CT did not show any interval change. To make a definitive diagnosis, video-assisted thoracic surgery was performed and the lesion was diagnosed as myxoid chondrosarcoma. In the 6-year postoperative follow-up, annual chest CT and bone scintigram did not reveal any abnormality, which excludes the possibility of a latent primary site other than the lung. Therefore, we considered the present case being of pulmonary origin. Accordingly, even though the lesion appeared unremarkable, surgical resection of solitary lung nodule should not be discouraged.

Phosphodiesterase type 4 inhibition of activated polymorphonuclear leukocytes in a simulated extracorporeal circulation model.

OBJECTIVES: Cardiopulmonary bypass is associated with a systemic inflammatory response syndrome and the risk of multiorgan injuries mediated by activated polymorphonuclear leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in polymorphonuclear leukocytes and plays a key role in the regulation of polymorphonuclear leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on the functional changes of polymorphonuclear leukocytes by using simulated extracorporeal circulation. METHODS: Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with and without 10 micro mol/L rolipram. F-actin content and L-selectin and CD11b expression of polymorphonuclear leukocytes were measured by means of flow cytometry. Polymorphonuclear leukocyte deformability was evaluated with a microchannel array flow analyzer that had a similar diameter as the capillaries. Polymorphonuclear leukocyte elastase was measured with an enzyme immunoassay. RESULTS: Rolipram reduced the increase of F-actin content of polymorphonuclear leukocytes and the increase of transit time of 100 micro L of blood sample through a microchannel. Rolipram reduced the increase of CD11b expression and the decrease of L-selectin expression of polymorphonuclear leukocytes. Rolipram reduced the release of elastase from polymorphonuclear leukocytes. CONCLUSION: Rolipram inhibited the deformability change mediated by F-actin assembly, the changes in adhesion molecules, and the release of elastase from activated polymorphonuclear leukocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be a feasible therapeutic strategy to prevent the exaggerated inflammatory response related to cardiopulmonary bypass.

Pulmonary adenocarcinoma with massive lymphocyte infiltration: report of three cases.

We report on three cases of pulmonary adenocarcinoma with lymphoid stroma. In these cases the lesions were small pulmonary adenocarcinomas, less than 2 cm in diameter, and histologically diagnosed as poorly or moderately differentiated adenocarcinomas. Histologically, the tumors were characterized by a small number of cancer cells and numerous infiltrating lymphoid cells, especially CD8 positive T-cell lymphocytes. No Epstein-Barr virus (EBV) genomes were demonstrated by in situ hybridization in the tumor cells of any of the tumors. Lobectomy and regional lymph node dissection were performed and intrapulmonary and mediastinal lymph node metastases were demonstrated in one of these cases (pT4N0M0, pT1N2M0 and pT1N0M0). Two patients are alive and the other died of pneumonia 26 months after the operation. None of the patients experienced recurrence of carcinoma. This unique type of adenocarcinoma characterized by massive lymphocyte infiltration could be referred to as "pulmonary adenocarcinoma with lymphoid stroma".

Intrabronchial orthotopic propagation of human lung adenocarcinoma--characterizations of tumorigenicity, invasion and metastasis.

Using the intrabronchial orthotopic propagation method, we evaluated the biological characteristics of human adenocarcinoma cell lines in vivo and examined the expressions of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and their related proteins. Nine human lung adenocarcinoma cell lines, including A549, NCI-H23, NCI-H322, NCI-H358, Calu-3, PC-14, LC-2/ad, RERF-LC-KJ and PL16T, were injected into the peripheral bronchi of mice using this method. The mice were sacrificed at 4 and 8 weeks after tumor cell propagation and the lungs and other organs were observed macroscopically and histologically. We classified the adenocarcinoma cell lines, according to their intrapulmonary tumorigenicity, into the following three groups: (A) those that showed a high incidence of intrapulmonary implantation (>50%) (A549 and NCI-H358). A549 showed mediastinal lymph node metastasis and pleural dissemination; (B) those that showed a low incidence of intrapulmonary implantation (PC-14, NCI-H322, NCI-H23, Calu-3, and LC-2/ad); (C) those that showed no tumorigenicity in the lung (RERF-LC-KJ and PL16T). In order to characterize the biological differences between each cell line, we investigated the expressions of MMP-2 and MMP-9 and their related molecules by northern blot analysis. The expressions of MMP-2 and MMP-9 and their activators (membrane-type 1-MMP and urokinase-type plasminogen activator) were thought to be associated with the growth, invasion and metastasis of the human lung adenocarcinoma cell lines examined.

Effect of relocating to areas of reduced atmospheric particulate matter levels on the human circulating leukocyte count.

A high level of atmospheric particulate matter induces an increase in circulating polymorphonuclear leukocyte (PMN) counts and an increase in serum inflammatory cytokine levels. The particulate level in Antarctica is extremely low compared with that in industrial countries. We hypothesized that this low level would reduce circulating leukocyte counts and serum inflammatory cytokine levels in people visiting Antarctica from industrial countries. The number density of particulates with aerodynamic diameters of <10.0 microm was measured in Japan and in Antarctica during the 41st Japanese Antarctic Research Expedition. Circulating leukocyte counts, granulocyte colony-stimulating factor and interleukin-6 levels, and pulmonary function were determined at regular intervals in 39 expedition members. The particulate number density was <1% of that measured in Japan. Total leukocytes, segmented and band-formed PMN, monocyte counts, and serum interleukin-6 levels decreased in Antarctica compared with the initial values measured in Japan. Pulmonary function parameters did not change except for maximal voluntary ventilation. Particulate matter levels had more significant effects on segmented PMN, band-formed PMN, and monocyte counts than cigarette smoking and the type of work. Exposure to reduced atmospheric particulates is considered to be a major factor for decreasing circulating leukocyte counts and serum cytokine levels.

High-dose concurrent chemo-proton therapy for Stage III NSCLC: preliminary results of a Phase II study.

The aim of this report is to present the preliminary results of a Phase II study of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted planning was made during the treatment. A total of 15 patients with Stage III NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up period was 21.7 months. None of the patients experienced Grade 4 or 5 non-hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1 in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non-proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and two patients, respectively. Severe ( ≥ Grade 3) leukocytopenia, neutropenia and thrombocytopenia were observed in 10 patients, seven patients and one patient, respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one patient each. Six patients (40%) experienced local recurrence at the primary site and were treated with 74 Gy RBE. Disease progression was observed in 11 patients. The mean survival time was 26.7 months. We concluded that high-dose PBT with concurrent chemotherapy is safe to use in the treatment of unresectable Stage III NSCLC.

Early-stage thymic carcinoma: is adjuvant therapy required?

Although the prognosis of advanced thymic carconoma remains poor, previous reports have shown survival rates of 70% to 100% in patients with Masaoka stage I or stage II of the disease who were treated with surgery followed by adjuvant therapy. However, the role of adjuvant therapy in these stages is controversial. We retrospectively evaluated the outcome of 4 patients with Masaoka stage II thymic carcinoma who were treated with surgery alone between 1992 and 2008. No patient had stage I of the disease. Primary tumors were preoperatively evaluated by chest X-ray and computed tomography. Needle biopsy was not performed because the tumors were clinically diagnosed as noninvasive thymomas. The largest diameter of the primary tumor was 65 mm. Mediastinal lymphadenopathy was not detected by computed tomography. All patients underwent transsternal thymectomy. Mediastinal lymph node dissection was not performed. None of the patients received adjuvant chemotherapy and/or irradiation. Histopathologic examination revealed squamous cell carcinoma in 3 patients and undifferentiated carcinoma in one. Pathologic invasion to the adjacent organs or lymph node metastasis was not detected. All patients were alive and free from relapse at a follow-up of 72 months (range, 12-167 months). Radical resection without adjuvant therapy could be a treatment option for early Masaoka stage thymic carcinoma with low-grade histology.

Preoperative lymphocyte count is an independent prognostic factor in node-negative non-small cell lung cancer.

A number of prognostic factors have been reported in non-small cell lung cancer (NSCLC). Although lymph node metastasis is the most poorly predictive value in completely resected NSCLC, a significant number of patients have a fatal recurrence even in node-negative curative NSCLC. Recently inflammatory response has been shown as a predictive value in NSCLC. Neutrophils and lymphocytes play an important role in cancer immune response. In this study, we retrospectively examined the impact of preoperative peripheral neutrophil and lymphocyte counts on survival, and investigated the relationships of these factors to clinicopathological factors in node-negative NSCLC. A total 237 patients were evaluated. When the cut-off value of neutrophil count was 4500 mm(-3) with a maximum log-rank statistical value, overall 5-year survival rates were 79.7% for the low-neutrophil-count group and 69.5% for the high-neutrophil-count group (P=0.04). When the cut-off value of lymphocyte count was 1900 mm(-3) with a maximum log-rank statistical value, overall survival rates were 67.9% for the low-lymphocyte group and 87.7% for the high-lymphocyte group (P<0.001). High-neutrophil-counts were associated with tumor size (P=0.002) and pleural invasion (P<0.001). Low-lymphocyte-counts were correlated with vascular invasion (P=0.018) and recurrence of NSCLC (P=0.01). Multivariate analysis showed that the lymphocyte count was an independent prognostic factor (hazard ratio: 3.842; 95% confidence interval: 1.827-8.078; P<0.001), but the neutrophil count was not (P=0.185). We conclude that a peripheral lymphocyte count, which is associated with vascular invasion, is an independent prognostic factor in node-negative NCSLC.

Limited thymectomy for stage I or II thymomas.

BACKGROUND: Once an anterior mediastinal tumor has been diagnosed as a thymoma, complete excision including the thymic gland and perithymic fat is currently the procedure of choice. However, little is known about the clinical outcome of grossly encapsulated thymomas excised only with the surrounding tissue while leaving a part of the thymic gland. METHODS: A retrospective historical comparative study was conducted on 79 patients who had received surgery for stage I (n=25) or stage II (n=54) thymomas. Total thymectomy was performed in 61 patients (Total Thymectomy Group), whereas resection of tumors with only the surrounding tissue was carried out in 18 (Limited Thymectomy Group). The follow-up interval was longer in the Limited Thymectomy Group because these patients were treated longer ago (104.2+/-58.1 months vs 67.3+/-54.8 months, p<0.05). RESULTS: One case in the Limited Thymectomy Group showed postoperative myasthenia gravis (5.6%). Two patients with multiple thymomas (2.5%) were treated with total thymectomy. One case in the Limited Thymectomy Group, which had been diagnosed as Masaoka stage II and WHO type B3 at initial surgery, recurred. None died of tumor progression in this study. Disease free survival rates at 10 years did not differ between the Limited Thymectomy and Total Thymectomy Groups (85.7% and 82.0%, respectively). There were no statistical differences in the incidence of postoperative myasthenia gravis and disease free survival between the two groups. CONCLUSION: Resection of thymomas with surrounding tissue instead of total thymectomy can be indicated for stage I or II thymomas in light of disease free and overall survival, post-operative onset of MG, and the incidence of multiple lesions.

Prone positioning improves distribution of pulmonary perfusion: noninvasive magnetic resonance imaging study in healthy humans.

The purpose of this study was to evaluate the effects of prone positioning on pulmonary perfusion using flow-sensitive alternating inversion recovery (FAIR), a noninvasive magnetic resonance imaging technique that requires no contrast medium. Seven healthy volunteers were studied in the supine and prone positions under three respiratory conditions: normal breathing of room air, unassisted breathing of 45% O2, and controlled mechanical ventilation (CMV) with positive end-expiratory pressure. Signal intensities (SIs) were obtained from ventral, middle, and dorsal regions on sagittal lung images and dependent/nondependent SI ratios were calculated to evaluate pulmonary perfusion distribution. In the supine position, SIs increased significantly from the ventral to dorsal region under all three respiratory conditions and prone positioning inverted the perfusion distribution under all conditions. Right lung SI ratios were 2.34 +/- 0.29, 2.74 +/- 0.66, and 2.42 +/- 0.73 in the supine position and 1.68 +/- 0.48, 1.78 +/- 0.36, and 1.92 +/- 0.21 in prone for room air, 45% O2, and CMV, respectively. The difference between supine and prone positions was statistically significant. The left lung showed a similar pattern and the difference was significant only under CMV. No difference was observed between the different respiratory conditions in both lungs. This study demonstrated that the distribution of pulmonary perfusion was more uniform in prone than in the supine position.

Pathologic radioresponse of preoperatively irradiated invasive thymomas.

BACKGROUND: We have been applying preoperative radiotherapy (RT) to Masaoka stage III thymomas intending to make surgical resection more complete by reducing mass volume, to prevent possible dissemination caused by surgical manipulation and to get better survival as a result. However, the radioresponses vary from tumor to tumor. We hypothesized that thymoma is a variable radioresponsive tumor depending on pretreatment histology. MATERIALS AND METHODS: Twenty-one of stage III thymomas underwent preoperative RT plus surgery followed by postoperative RT between 1982 and 2004. Reduction ratios, histopathologic changes according to WHO histologic criteria, resectability, long-term survival, and disease control, by preoperative RT were analyzed. RESULTS: Pretreatment WHO subtypes were type AB (n = 1), B1 (5), B2 (6), B3 (4), and unclassified (5). Sixteen tumors (76.2%) decreased in size after preoperative RT with a mean (median) reduction ratio of 30.8% (27.0%). Type B1or B2 group had higher reduction ratio than type B3 group (mean value of 39.7%, 31.8%, and 21.0%, respectively, p < 0.01). Histopathologically, lymphocyte diminished markedly in type B1 thymoma, and both lymphocyte and epithelial cells diminished in type B2, whereas none of the B3 tumors showed any histologic change. The values of all the cases is 90.5% in complete resection, 19.0% in no combined resection of the adjacent organs, and 77.6% and 83.6% in overall and disease-free 10-year survival, respectively, and these value do not differ according to the WHO histologic criteria. CONCLUSIONS: This modality at modest doses was macroscopically and histopathologically effective on tumors particularly in WHO B1 and B2 thymomas than WHO B3 thymoma. The therapeutic benefit of preoperative RT followed by surgery and postoperative RT for stage III thymomas should be defined thoroughly.