Kaoru Ondo

Reduced expression of thrombospondin-1 correlates with a poor prognosis in patients with non-small cell lung cancer

Thorombospondin-1 (TSP-1) is a 450 kDa extracellular matrix glycoprotein, with anti-angiogenic activity. We analyzed the relationship in TSP-1 expression and Microvessel count (MVC), and also clinical factors, using immunohistochemical methods for non-small cell cancer (NSCLC). Histopathologically, there was inverse correlation between TSP-1 expression and MVC for squamous cell carcinoma, but not for adenocarcinoma cases. Among 199 completely resected cases of NSCLC, the 5-year survival was 77.0% when the expression of TSP-1 was maintained and 55.1% when the expression were reduced, respectively (P=0.0046). When compared with TSP-1 expression in the high MVC subgroup, there was significantly shorter survival time when TSP-1 expression was reduced (P=0.0091), and no significant difference was seen for the low MVC subgroup. Multivariate analysis revealed that expression of TSP-1 is as a prognostic factor of NSCLC. Our present data suggest that TSP-1 might not be a direct anti-angiogenic factor and the TSP-1 expression is a prognostic indicator of NSCLC.

Postoperative adjuvant adoptive immunotherapy with lymph node-LAK cells and IL-2 for pathologic stage I non-small cell lung cancer

We conducted a clinical trial of adoptive immunotherapy with lymph node-lymphokine-activated killer (LN-LAK) cells and recombinant interleukin 2 (rIL-2) for a surgical adjuvant therapy of pathologic stage I non-small cell lung cancer. The regimen consisted of the subcutaneous administration of low-dose rIL-2 for 6 consecutive days and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of surgical operation. A group of 19 patients with primary lung cancer received the immunotherapy about 2 weeks after surgery (pulmonary lobectomy). The regimen was postoperatively well tolerated by the patients. In peripheral blood lymphocytes (PBL) obtained after the treatment, the proportion of CD3+ T cells predominantly increased with the increase of CD4+ T cell subsets. On the other hand, the proportion of CD20+ B cells decreased. Both NK and LAK activity of PBL significantly increased. However, the immunomodulatory effects did not result in a prolongation of the postoperative survival time in comparison to the postoperative survival of patients (n = 21) with surgery alone during the same period. These results suggested that the treatment with low-dose LN-LAK cells and concurrent low-dose IL-2 could, therefore, neither reduce nor eradicate minimal micrometastatic diseases.

Cystic Schwannoma Presenting as Massive Hemoptysis in an Adult

A 62-year-old man who presented with the chief complaint of hemoptysis is reported. A chest radiograph obtained on admission showed a huge cystic mass located at the posterior mediastinum. Prior to surgery, transarterial embolization was done because of continuous massive hemoptysis. An uneventful removal of the tumor was performed, and the pathological diagnosis was schwannoma. The hemoptysis was thought to have been caused by changes in the cystic formation in combination with inflammation which extended to the lung.

Analysis of various treatments for pulmonary aspergillomas.

Abstract The objective of this study was to analyze the results of various treatments for pulmonary aspergilloma and to determine the surgical indications. A total of 41 patients with pulmonary aspergilloma hospitalized at the National Minamifukuoka Chest Hospital between 1973 and 1999 were analyzed with regard to their response to treatment and long-term prognosis. Five asymptomatic patients who were untreated demonstrated no change in the clinical status of aspergilloma. Analysis of the short-term response revealed surgery to be the most effective treatment. Systemic and intracavitary injections of antifungal drugs were not definitely effective, although they had a positive effect in some patients. A survival analysis revealed that all eight patients who underwent surgery are still alive. Using the Cox proportional hazard model, it was found that the favorable prognostic factors were the absence of symptoms, the absence of a superimposed bacterial infection, and surgery. There were ten deaths: three from lung cancer and seven related to uncontrollable superimposed bacterial infections, often resulting in hemoptysis. We conclude that patients with asymptomatic pulmonary aspergillomas should be clinically observed for signs of the development of lung cancer, but do not require active treatment. On the other hand, patients who are symptomatic and have uncontrollable superimposed bacterial infection will benefit from surgery.

Clinical Course and Management of Patients Undergoing Open Window Thoracostomy for Thoracic Empyema

Background: While open window thoracostomy (OWT) is a safe procedure and is indicated in patients who have thoracic empyema either with or without a bronchopleural fistula, it may prolong the hospital stay. Objectives: We retrospectively analyzed the relationship between the etiology of thoracic empyema and the open window interval (OWI). Methods: Between January 1986 and May 1997, 53 patients resistant to conventional therapy underwent OWT for thoracic empyema at the Department of Surgery of the National Minami-Fukuoka Chest Hospital. The patients were classified into five groups based on the etiological findings of thoracic empyema. 44 patients also underwent closure of the window until June 1999. Results: The average OWI was 180.4 ± 51.9 (mean ± SE) days for postoperative empyemas in lung cancer, 128.0 ± 32.1 days for bacterial nontuberculous empyemas, 189.6 ± 24.1 days for fungal empyemas, 365.8 ± 201 days for empyemas caused by atypical mycobacteria and 322.0 ± 58.7 days for tuberculous empyemas. There was no evidence that the OWI was related to either sex, age, etiology of thoracic empyemas, performance status, the existence of bronchopleural fistulae, complications of diabetes mellitus or preoperative malnutrition status in multivariable models. 5 patients underwent a second OWT because of recurrence of empyema. Mortality rate was 7.5%. Conclusions: There was no relationship between clinical factors including nutritional assessment and OWI. OWT generally is a safe and effective procedure for thoracic empyema resisting to conventional therapy except that it can make an extended hospital stay necessary.

Concurrent chemoradiotherapy using cisplatin plus s-1, an oral fluoropyrimidine, followed by surgery for selected patients with stage III non-small cell lung cancer: A single-center feasibility study

PurposeThis single-institutional study was designed to determine whether S-1, an oral fluoropyrimidine, plus cisplatin with concurrent radiotherapy is feasible as an induction treatment for locally advanced non-small cell lung cancer (NSCLC).MethodsEighteen patients were analyzed in this study from July 2005 to March 2008. The patients received 40 mg/m2 S-1 orally twice per day on days 1 through 14 and 22 through 35, and cisplatin (60 mg/m2) was injected intravenously on days 8 and 29. The patients also underwent radiotherapy, and received a total dose of 40 Gy in 20 fractions beginning on day 1. Surgical resection was performed from 3 to 6 weeks after completing the induction treatment.ResultsNine (50%) of the 18 patients who received the induction treatment achieved a partial response. One patient refused to undergo surgery. The remaining 17 patients underwent a complete surgical resection. There were no deaths nor any major morbidities during the perioperative period. The recurrence-free survival and overall survival rate at 2 years for the patients who underwent resection were 63.3% and 88.2%, respectively.ConclusionInduction treatment using S-1 plus cisplatin and concurrent radiotherapy and surgical resection for selected patients with stage III NSCLC is a feasible and promising new treatment modality.

Direct IFNluence of interferon-γ on proliferation and cell-surface antigen expression of non-small cell lung cancer cells

In order to clarify the anti-tumor activity of IFN-gamma, we investigated the direct IFNluence of IFN-gamma on both the growth and cell-surface antigen expression of tumor cells. In the present study, four human lung cancer cell lines were used; two squamous cell lines (QG-56, QG-95) and two adenocarcinoma cell lines (PC-9, PC-12). In all four tumor cell lines, mutations were detected in exon 7 of the p53 gene by a PCR-FSSCP analysis. The proliferation of QG-56 or QG-95 was inhibited by IFN-gamma in a dose-dependent manner with about 70% inhibition at 1000 JRU/ml while that of PC-9 was slightly inhibited with maximally 25% inhibition at 1000 JRU/ml. The growth of PC-12 was not inhibited at all. In QG-56, QG-95 and PC-9, the fraction of cells in G1 phase increased while the fractions of cells in both S and G2/M phases decreased after exposure to IFN-gamma (200 JRU/ml) for 72 h. The growth inhibition by long-term exposure to IFN-gamma was irreversible in QG-56. After culture in the presence of IFN-gamma (200 JRU/ml) for 14-16 days, tumor cells were examined for expression of various antigens, including HLA-class I, HLA-class II, and CEA. In all cell lines but PC-12, 100% of cells expressed HLA-class I after incubation with IFN-gamma. Both HLA-class II and CEA were also induced in those cell lines. The proportion of HLA-class II-positive cells or that of CEA-positive cells varied among the cell lines. Of the three antigens, the degree of HLA-class II expression paralleled that of growth inhibition by IFN-gamma treatment. These results suggested that in various function of IFN-gamma against tumor cells, the anti-proliferative effect might be closely linked with the induction of HLA-class II probably through a similar posttranscriptional process, independent of the function of p53 gene.

Pulmonary Blastoma in an Adult: A Case with Rapid Progression

A case of biphasic type pulmonary blastoma in a 59-year-old man is reported. Although the tumour was radically resected, there was rapid metastasization to the neck, mediastinum, liver and multiple bones. Despite radiotherapy, the patient died about 14 months postoperatively. Close follow-up and aggressive chemotherapy should be considered for such tumours.

Subcarinal bronchogenic cyst with high carbohydrate antigen 19-9 production

In a rare case of bronchogenic cyst with high carbohydrate antigen (CA) 19-9 production, a 57-year-old man with coughing and chest pain was diagnosed with a subcarinal mediastinal tumor. Fiberoptic bronchoscopy showed an erosive mucosal lesion overlying the area of extrinsic compression at the membranous of the right mainstem bronchus. Serum carbohydrate antigen 19-9 was elevated at 1300 U/ml. Thoracotomy showed an encapsulated cyst tightly adhering to the right main bronchus. The cyst was extirpated after ablation at the adherent cystic wall by electrocautery. Although intracystic carbohydrate antigen 19-9 concentration was very high, serum carbohydrate antigen 19-9 and bronchoscopic findings returned to normal postoperatively. The histological diagnosis was consistent with a bronchogenic cyst and carbohydrate antigen 19-9 could be immunohistochemically demonstrated within its epithelium.

Rib metastasis appearing 8 years after surgery for lung cancer: Report of a case

A 39-year-old man underwent a right upper lobectomy and lymph node dissection for right lung adenocarcinoma on March 7, 1988. He was referred for an evaluation of a systemic bone scintillation scan on October 29, 1996. A hot spot at the right fourth rib was recognized. After performing needle aspiration cytology, a diagnosis of adenocarcinoma was made. This case was considered to be rib metastasis occurring 8 years after surgery for lung cancer. In general, regular follow-up examinations are performed for at least 5 years after surgery; however, surgeons should also keep such late metastatic cases in mind.