Yasuki Saito

Prognostic assessment of 1310 patients with non-small-cell lung cancer who underwent complete resection from 1980 to 1993.

OBJECTIVE The TNM staging system of lung cancer is widely used as a guide for estimating prognosis and selecting treatment modality. In 1997, the International Union Against Cancer and the American Joint Committee on Cancer have adopted a revised stage grouping for lung cancer. However, the validity of the new stage grouping has not been fully established. We investigated the prognoses of patients who had resection of non-small-cell lung cancer to confirm the validity of the revised classification. METHODS A total of 1310 patients with non-small-cell lung cancer underwent complete resection and pathologic staging of the disease in our hospitals from 1980 through 1993. A pulmonary resection was performed with a systematic nodal dissection. The survivals were calculated with the Kaplan-Meier method on the basis of overall deaths, and the survival curves were compared by log rank test. RESULTS There were significant differences in survival between patients with T1 N0 M0 and T2 N0 M0 disease and between those with T1 N1 M0 and T2 N1 M0 disease. However, there was no significant difference between patients with T2 NO M0 disease and those with T1 N1 M0 disease. No significant difference in survival was observed among patients with T2 N1 M0, T3 NO M0, and T3 N1 M0 cancer. Patients with different invaded organs of T3 subdivision (pleura, chest wall, pericardium, or diaphragm) had a different prognosis. There was no significant difference between patients with T3 N2 M0 disease and those with stage IIIB disease. CONCLUSIONS We supported most of the revision, such as dividing stage I, dividing stage II, and putting T3 N0 M0 to stage IIB. Furthermore, we found some candidates for a subsequent revision, such as putting T3 N1 M0 to stage IIB, putting T2 N0 M0 and T1 N1 M0 together, regarding diaphragm invasion as T4, and putting T3 N2 M0 to stage IIIB.

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery

OBJECTIVE A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer (NSCLC). PATIENTS AND METHODS From March 1992 to December 1994, 221 patients with completely resected stage I-II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil plus Tegafur (UFT) (adjuvant group, 109 patients), and surgical treatment alone (control group, 110 patients). RESULTS The overall 5-year survival rates were 79% for the adjuvant group and 75% for the control group, and there was no statistical significance. The 5-year disease-free survival rates were 78% for the adjuvant group and 71% for the control group, and there was also no statistical significance. There have been seen no severe complications in the adjuvant group. The mean total dosages of UFT were about 75% of maximum basic amount. CONCLUSIONS The UFT regimen was feasible. However, we have not observed any survival benefit in the adjuvant group. Larger trials are needed to confirm the effect of UFT to patients with resected NSCLC.

Occult lung cancer beyond bronchoscopic visibility in sputum-cytology positive patients

Sputum cytology is useful for screening and diagnosis of centrally located lung cancer in Japan. On the other hand, cancer beyond the range of bronchoscopic visibility in X-ray negative patients can be detected only with difficulty. Of 265 patients detected by sputum cytology in mass screening, 85 had an abnormal chest roentgenogram and the remaining 180 were roentgenographically occult. A total of 200 roentgenographically occult squamous cell carcinoma lesions were detected in the above 180 patients. A total of 45 of the 200 lesions were bronchoscopically occult. Twenty-two of the above 45 lesions were beyond the range of bronchoscopic visibility with a standard bronchoscope. The data obtained show that a sputum cytology positive, X-ray negative squamous cell carcinoma may lie outside the reach of a flexible bronchoscope. Thus, when it is difficult to localize a cancer, brushing of the peripheral bronchi beyond bronchoscopic visibility and chest computed tomography should be performed.

Identification of a 910-Kb region of common allelic loss in chromosome bands 16q24.1–q24.2 in human lung cancer

To understand the molecular pathogenesis of human lung cancer, we analyzed allelic deletions on the long arm of chromosome 16 by PCR amplification of microsatellite markers. A total of 203 lung cancer specimens (78 squamous cell carcinomas and 125 adenocarcinomas) were analyzed. In both cell types, a common region of allelic loss was identified in 16q24.1–q24.2; it is flanked by the two markers D16S534 and D16S422 that spanned at most 910 kb. These results were confirmed by fluorescence in situ hybridization. There was no correlation between allelic loss and histopathologic diagnosis or clinical stage. These results suggest the existence of a tumor‐suppressor gene that plays an important role in the course of carcinogenesis in both squamous cell carcinoma and adenocarcinoma of the lungs. Genes Chromosomes Cancer 22:1–8, 1998.

A Therapeutic Approach to Roentgenographically Occult Squamous Cell Carcinoma of the Lung

The significance of limited resections, including wedge resection and segmentectomy, remains controversial because of their curability rates. In the current study, the objective was to determine a strategy for the treatment of patients with roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC) based on the pathologic findings from 184 patients with ROSCC who underwent resection.

The efficacy of lung cancer screening conducted in 1990s: four case/control studies in Japan

The efficacy of lung cancer screening is still controversial. In order to evaluate efficacy of mass screening for lung cancer in 1990s, the Japanese Ministry of Health and Welfare planned to conduct four independent case-control studies in four different regions; Miyagi, Gunma, Niigata, and Okayama Prefecture. The study design of all the four studies was a matched case-control study in which the decedents from lung cancer were defined as cases. In Gunma Prefecture, a screening examination is annual miniature chest X-ray only, whereas sputum cytology is added for high-risk screenees in others. Matching conditions were gender, year of birth, smoking histories (except Okayama), and municipality. Smoking adjusted odds ratio (OR) of dying from lung cancer for those screened within 12 months before case diagnosis compared with those not screened ranged 0.40-0.68. Three of four studies revealed statistically significant reduction of the risk for lung cancer death. OR of pooled analysis, where all sets were combined and analyzed, was 0.56 (95% confidence interval: 0.48-0.65). Recent mass screening program for lung cancer in Japan could reduce the risk for lung cancer death. However, the possibility exists that some confounding factors affected the results. In order to elucidate whether the results can be applied to Western countries, further studies will be required.

Five‐year survivors with resected PN2 nonsmall cell lung carcinoma

Some patients with resected pN2 lung carcinoma were long term survivors. To determine appropriate therapeutic modalities for the selected patients, the clinicopathologic characteristics of these patients were examined using the actual number of survivors rather than the cumulative survival rate because the cumulative survival rate occasionally is confounded due to patients with short follow‐up periods.

Clinicopathological analysis of 19 cases of isolated carcinoma in situ of the bronchus

Nineteen cases of isolated squamous cell carcinoma in situ (CIS) of the bronchus were described clinicopathologically from among 149 male heavy smokers with roentgenographically occult lung cancer discovered mainly by mass screening performed from 1982 to 1991. All 19 patients had positive sputum cytology tests and negative chest x-ray films and underwent lobectomy (except one who had segmentectomy because of poor lung function). Prior to operation, localization was accomplished by one to eight bronchoscopies using repetitive brush cytology and biopsy. Five cases were bronchoscopically invisible. Polypoid protuberance was noted in three cases, micronodular swelling in three, thickening of spur in five, and mucosal granularity in three. Histology by serial block sectioning showed that there was no nodal involvement in any cases; the maximum length or diameter was 12 mm. Thirteen tumors were 4≤ mm, four of which were confined to the spur where they occurred. Follow-up data showed a favorable prognosis. Segmentectomy or sleeve resection of bronchus without mediastinal lymph node dissection may be adequate for CIS

Clinical and prognostic assessment of patients with resected small peripheral lung cancer lesions

One hundred fifteen patients with small (≦2 cm in diameter) peripheral lung cancer lesions underwent surgical treatment in the Department of Surgery, the Research Institute for Chest Diseases and Cancer, Tohoku University, Miyagi Prefecture, Japan. the authors investigated several prognostic factors of these cases. the 5‐year survival rate of these 115 patients was 70%. Various factors such as histologic type, nodal involvement, pleural involvement, pathologic stage, and curativity of the operation were revealed to affect survival significantly. in patients with and without nodal involvement, there was no significant difference between the survival rate of patients with lung cancer lesions smaller than 2 cm and those with lesions 2.1 to 3 cm. However, the rate of lymph node metastasis was significantly different in the group with lesions smaller than 2 cm compared with those with lesions 2.1 to 3 cm (21% versus 43%, respectively).

Clotrimazole, an imidazole antimycotic, is a potent inhibitor of angiogenesis.

Clotrimazole, an imidazole antimycotic, interferes with the rise in cytosolic Ca2+ and inhibits cell proliferation in a reversible manner. Here we describe the effect of clotrimazole on vascular endothelial cells (ECs). Clotrimazole inhibited the proliferation of ECs stimulated with typical angiogenic growth factors; vascular endothelial growth factor and basic fibroblast growth factor (bFGF). This inhibitory effect of clotrimazole was dose‐dependent and the maximal inhibition was observed at a concentration of 10 mM. We did not observe any increase in 51Cr release from ECs during treatment with 10 μM. clotrimazole. Moreover, clotrimazole inhibited the basal and bFGF‐stimulated migration of ECs. As clotrimazole inhibited two principle components of angiogenesis; the proliferation and migration of ECs, we examined whether clotrimazole inhibited angiogenesis. Tube formation by ECs in type 1 collagen gel was investigated, and clotrimazole was found to be significantly inhibitory. The inhibitory effect of clotrimazole on angiogenesis was further confirmed in an in vivo angiogenesis model of murine Matrigel plug assay. These results demonstrate that clotrimazole is a potent inhibitor of angiogenesis.