Vascular endothelial growth factor mRNA and protein expression in airway epithelial cell lines in vitro.

Vascular endothelial growth factor (VEGF) plays multifunctional roles in vascular permeability, repair and remodelling processes, in addition to the maintenance of vascular structure and function. In the present study, the potential of airway epithelial cell lines, BEAS-2B cells and A549 cells, to release and express VEGF in unstimulated and stimulated conditions was evaluated. The secretion and expression of VEGF were evaluated by enzyme-linked immunosorbant assay and by reverse transcriptase-polymerase chain reaction. The isoforms of released VEGF were determined by high-performance liquid chromatography. BEAS-2B cells and A549 cells released VEGF constitutively. Interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha augmented the release of VEGF in a time- and dose-dependent manner. The released VEGF was 165 amino acid residues in either condition. Pseudomonas aeruginosa lipopolysaccharide (LPS), interferon (IFN)-gamma, smoke extract (SE), neutrophil elastase (NE), and bradykinin stimulated the release of VEGF. Keracinocyte growth factor (KGF), which reduces vascular permeability, also stimulated both cells to release VEGF. VEGF messenger ribonucleic acid (mRNA) was expressed both time- and dose-dependently at 2 h, and declined after 2 h in response to IL-1beta and TNF-alpha. The expression of VEGF mRNA in airway epithelial cells was also augmented by LPS, IFN-gamma, SE, NE, and KGF stimulation. These data suggest that airway epithelial cells may regulate the maintenance of vascular structure and function, as well as vascular permeability, repair and remodelling processes, in a variety of lung conditions by expressing vascular endothelial growth factor.

Recurrence of thymoma: clinicopathological features, re-operation, and outcome.

BACKGROUND: Even after complete resection, recurrence of thymoma is not infrequently observed, and treatment of recurrent thymoma remains controversial. STUDY DESIGN: One hundred and twenty-six patients underwent surgically complete resection for thymoma, and 24 of them had a recurrence. Surgical treatment of recurrent thymoma was attempted in 15 patients for a total of 18 times. In the present study, the relevance of clinicopathological features and the re-operation on the survival rate after the recurrence were determined. RESULTS: The most frequent recurrent type was pleural dissemination (92%), with local recurrence observed in 5%. Overall 5- and 10-year survivals after recurrence were 37 and 16%, respectively. Disease-free interval after initial operation and complication of myasthenia gravis had no significant effect on postrecurrent survival. The use of postoperative mediastinal irradiation had no effect on reducing the recurrence rate or improving survival after recurrence. Two of 15 patients who underwent re-operation died of major complications after It. pleuropneumonectomy for severe pleural dissemination. In the present study, the re-operation was not significantly effective for prolongation of postrecurrence survival. CONCLUSION: Our study showed that re-operation should not be attempted for all patients with recurrent thymoma. Because effect of subtotal resection for severe pleural recurrence is disappointing, total resection for minimal pleural dissemination or small local recurrence will be undertaken to improve postrecurrent survival. Careful follow-up for > 10 years will increase the chance of the total resection of the recurrent thymoma.

[Clinical study of operated nine thymic carcinomas].

Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median-sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma.

[Assessment of the new TNM classification for resected lung cancer].

To evaluate the revised TNM classification, we investigated the prognoses of 552 consecutive patients who had resection of non-small-cell lung cancer between April 1982 and March 1996. According to the new classification, the 5-year survival rate was 76.9% for stage I A, 57.2% for stage I B (I A versus I B, p < 0.0005), 47.7% for stage IIA, 49.8% for stage IIB, 18.6% for stage IIIA (IIB versus IIIA, p = 0.005), 16.7% for stage IIIB, and 7.9% for stage IV (IIIB versus IV, p = 0.02). Especially for patients in stage I A, there was significant difference in survival between patients with the tumor size within 1.5 cm and those with larger than 1.5 cm. The survival rate for T3N0M0 patients was significantly better than that for T3N1-2M0, but there was no significant difference between patients with T3N0M0 disease and those with T2N1M0 disease. Concerning the pm1 patients, the survival rate was significantly better than other stage IIIB patients. Our results supported the revision for dividing stage I and putting T3N0M0 into stage IIB. However, the classification is controversial about dividing stage II and putting pm1 as T4 disease. Furthermore, subgrouping of T1N0M0 disease by tumor size, T3 by tumor invaded organ will be necessary in the next revisions.

Intrapleural rupture of a cystic thymoma.

Although cystic degeneration of a thymoma is not uncommon, rupture of a cystic thymoma is rare. The authors report a patient with sudden chest pain and dyspnea due to rupture of a cystic thymoma into the right pleural space.

Solitary aneurysm of the innominate vein.

Two cases of isolated saccular aneurysms of the innominate vein are presented that appeared as mediastinal masses. Contrast-enhanced computed tomography (CT) allowed for accurate diagnosis in one patient, while the second patient had atypical CT findings that led to thoracotomy for proper diagnosis. A diagnosis of innominate vein aneurysm should be considered when a uniform attenuation mediastinal mass is seen on CT so that unnecessary biopsy and surgery can be avoided.

Bradykinin stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activity.

Activation of the kallikrein-kinin system in lung injury has long been recognized. However, the effects of bradykinin (BK) on human lung fibroblasts (HLF) remain to be elucidated. We determined whether BK stimulates HLF to release chemotactic activity for neutrophils and monocytes (NCA and MCA, respectively). We evaluated HLF supernatant fluids for chemotactic activity through a blind-well chamber technique. HLF released NCA and MCA in a dose- and time-dependent manner in response to BK. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular sieve column chromatography revealed that both NCA and MCA had multiple chemotactic peaks. NCA was inhibited by a leukotriene (LT) B(4) receptor antagonist and by antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF). MCA was attenuated by the LTB(4) receptor antagonist and by antibodies to monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and transforming growth factor (TGF)-beta. Both the LTB(4) receptor antagonist and these antibodies inhibited chemotactic activity of the molecular weights corresponding to MCP-1, GM-CSF, and TGF-beta, separated by column chromatography. The concentrations of IL-8, G-CSF, MCP-1, GM-CSF, and TGF-beta in supernatant fluids increased significantly in a time-dependent manner in response to BK. The receptors responsible for the release of NCA, MCA, and individual chemokines included both BKB(1) and BKB(2) receptors. These data suggest that BK may stimulate lung fibroblasts to release inflammatory cytokines, which may modulate lung inflammation.

[Two cases of the bronchial cyst located in the anterior mediastinum].

Bronchial cysts are common cystic tumors around the tracheobronchial tree in the middle and posterior mediastinum and rarely locate in the anterior mediastinum. We reported two cases of the bronchial cyst located in the anterior mediastinum. One case was a 57 year-old-female. A thymic cyst was suspected and the extended total thymectomy was performed through the mediansternotomy. The microscopic examination showed bronchial epithelium and cartilage in the cystic wall. The another case was 71 year-old-male operated by thoracoscopic surgery for the cystic tumor in the anterior mediastinum. Microscopic examination showed bronchial epithelium and gland in the cystic wall.

[A case of thymic carcinoid with multiple endocrine neoplasm (MEN)-type I].

We presented a case of thymic carcinoid with MEN type I. A 43-year-old woman who followed at MEN type I for 4 years was pointed out an abnormal shadow by chest X-ray. Chest CT levealed the presence of two anterior mediastinal tumors. Extended total thymectomy was performed through the median sternotomy. There were 3 tumors in thymus. Histological examination revealed three tumors in the thymus and all of the tumor were diagnosed carcinoid. Our experience suggests that CT or MRI of the chest should be considered as part of clinical screening in patients with MEN type I.

[An evaluation of pathologic T3 lung cancer].

A total of 35 pT3 patients of lung cancer underwent pulmonary resection from 1983 to 1997 in our department. The overall five-year survival rate of the 35 cases was 35.8%. There was no significant difference between the five-year survival rate of squamous cell carcinoma and that of adenocarcinoma. A superior outcome was observed for cases of curative resection compared with that of non-curative resection. Five-year survival rates of 19 patients with N0 disease, 16 patients with N1 or N2 disease were 46.6% and 22.2% respectively (p < 0.05). There was no significant differences among the survival rates according to the site of tumor invasion. We concluded that the long-term survival of patients with pathologic T3 disease critically depended on the lymph node state and completeness of resection.