Yohsuke Ohtake

Prognostic Significance of Apoptotic Index in Completely Resected Non–Small-Cell Lung Cancer

PURPOSE To evaluate the significance of apoptotic index (AI) as a prognostic factor after surgery for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS A total of 236 patients who underwent surgery for previously untreated pathologic stage I to IIIa NSCLC between 1985 and 1990 were reviewed. AI was defined as the number of apoptotic cells, detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling, per 1,000 tumor cells. Proliferative index (PI) and aberrant p53 expression were also evaluated immunohistochemically. RESULTS The 5-year survival rate for the lowest-AI group (AI < 5.0) was 74.7%; those for the lower-AI group (5.0 < or = AI < 11.0) and the higher-AI group (11.0 < or = AI < 25.0) were 51.6% and 57.8%, respectively. These survival rates were significantly lower than that of the lowest-AI group (P =.021 and P =.043, respectively). The highest-AI group (25.0 < or = AI), however, showed the most favorable prognosis, with a 5-year survival rate of 83.2%. Multivariate analysis confirmed that a moderate AI (5.0 < or = AI < 11.0 or 11.0 < or = AI < 25.0) was a significant factor to predict poor prognosis. The PIs for the lowest-, the lower-, the higher-, and the highest-AI groups were 32.3%, 48.0%, 54.3%, and 50.7%, respectively. The lowest-AI group showed a favorable prognosis because of its low PI, whereas the lower- and the higher-AI groups had a poor prognosis caused by increased cancer-cell proliferation. The highest-AI group showed the most favorable prognosis because apoptotic cell death overcame cell proliferation. No significant correlation was observed between AI and aberrant p53 expression. CONCLUSION AI proved to be an independent prognostic factor in NSCLC.

A new method of segmental resection for primary lung cancer: intermediate results.

OBJECTIVE To improve the postoperative results of limited resection for small lung cancer, we have developed a new operative method, pulmonary artery-guided segmentectomy. This resection begins with identification of the pulmonary arterial branches involved in the tumor, then the pulmonary tissue is divided along the pulmonary arteries (i.e. guided by pulmonary arteries) from the hilum toward the periphery by electrocautery. The advantages of this method include the facilitation of securing adequate margin from the tumor, and the feasibility of intralobar lymph node dissection during operation. To examine the efficacy of the new method of segmental resection, we retrospectively reviewed 74 cases of T1N0M0 disease who underwent the pulmonary artery-guided segmentectomy. METHODS From 1993 to 2000, 74 patients with pathological T1N0M0 lung cancer were treated by the pulmonary artery-guided segmentectomy. Forty-one patients (55.4%) who underwent the segmentectomy had been considered suitable candidates for lobectomy (intentional resection group). The other 33 patients (44.6%) were considered poor candidates for lobectomy because of poor cardiopulmonary reserve (compromised resection group). RESULTS The overall survival rate at 5 years was 82.0%. The 5-year survivals in the intentional and the compromised resection groups were 81.6 and 77.6%, respectively, and no significant differences were detected between the groups. According to tumor size, the 5-year survival rate for patients with tumors of 20 mm or smaller (92.9%, n=53) was higher than that for the patients with tumors of 21-30 mm (63.0%, n=21), but the difference did not reach statistical significance. Median follow-up time of 27.0 months revealed eight locoregional recurrences and four deaths due to lung cancer. Sixty-three patients (85.1%) are alive with no evidence of disease, and six patients (8.1%) are alive with recurrent disease. Locoregional recurrences occurred in one of 53 patients (1.9%) with tumors 20 mm or smaller and in seven of 21 patients (33.3%) with tumors 21-30 mm, the difference being statistically significant (P<0.01). CONCLUSIONS Our intermediate results demonstrated that the new pulmonary artery-guided segmentectomy could be an alternative method for selected patients with small lung cancer, particularly with tumors 20 mm or smaller in diameter.

Advantage of post-operative oral administration of UFT (Tegafur and Uracil) for completely resected p-stage I-IIIa non-small cell lung cancer (NSCLC)

OBJECTIVE Although adjuvant therapy after surgery for non-small cell lung cancer (NSCLC) has been reported to be ineffective, it has been recently reported in prospective randomised studies conducted by two different groups in Japan that oral administration of a 5-fluorouracil (5-FU) derivative drug, UFT (a combination drug of tegafur and uracil) can improve the post-operative survival [The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan). A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). Eu J Surg Oncol 1995;21:69-77; Wada, H., Hitomi, S., Teramatsu, T, West Japan Study Group for Lung Cancer Surgery. Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. J Clin Oncol 1996;14:1048-1054]. To examine the efficacy of UFT as post-operative adjuvant therapy, a retrospective study was performed. METHODS A total of 655 consecutive patients who underwent complete tumor resection for pathologic stage I-IIIa, NSCLC at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1976 and 1992 were retrospectively reviewed. As post-operative adjuvant therapy, UFT was administrated to 98 patients (UFT group), and was not administered to the other 557 patients (Control group). RESULTS The 5-year survival rate of the UFT group was 76.5%, which was significantly better than that of the Control group (5-year survival rate: 58.6%, P = 0.005). Stratified with pathologic stage, the efficacy of UFT was seen in the p-stage I disease (5-year survival rate: 88.6% for the UFT group, 72.0% for the Control group, P = 0.013) and in the p-stage IIIa, pN2 disease (5-year survival rate: 54.3% for the UFT group, 37.5% for the Control group, P = 0.037). Multivariate analysis of the prognostic factors also revealed the efficacy of UFT (P = 0.004, 95% confidence interval of relative risk: 0.325-0.840). Post-operative intravenous chemotherapy or radiation therapy did not prove to be significant factors affecting the prognosis. CONCLUSIONS Efficacy of oral administration of UFT as post-operative adjuvant therapy for completely resected NSCLC was proposed. To confirm the efficacy, a prospective randomized study for a more homogenous patient group is needed.

p53 Status Predicts the Efficacy of Postoperative Oral Administration of Tegafur for Completely Resected Non‐small Cell Lung Cancer†

Although postoperative adjuvant therapy for non‐small cell lung cancer (NSCLC) had not been reported to be effective, it has been reported recently that oral administration of tegafur (1‐[2‐tetrahydrofuryl]‐5‐fluorouracil, FT) may improve the postoperative prognosis. In the present paper, to examine whether p53 status affects the efficacy of FT as postoperative adjuvant chemotherapy for NSCLC, a total of 236 consecutive patients with completely resected pathologic stage I–IIIa NSCLC were retrospectively reviewed. p53 status was determined by immunohistochemical staining. For all patients, the 5‐year survival rate of patients with FT administration (FT group) was 78.1%, being significantly higher than that (69.1%) of patients without FT administration (control group) (P=0.046). For patients without immunohistochemical evidence of p53 overexpression, the 5‐year survival rate in the FT group was 87.1%, being significantly higher than that (74.0%) in the control group (P=0.036). This demonstrates an improvement of postoperative prognosis by FT administration. On the other hand, for patients with p53 overexpression, there was no significant difference in the postoperative prognosis between the FT group and the control group (5‐year survival rate 63.2% and 60.1%, respectively; P=0.514), demonstrating that FT administration was not effective for these patients. In conclusion, p53 status may be useful for predicting the efficacy of postoperative adjuvant chemotherapy using FT. A prospective randomized study stratified by p53 status is needed to clarify the effect of postoperative FT administration.

Lewis Y antigen expression and postoperative survival in non–small cell lung cancer

BACKGROUND In contrast to other Lewis blood group-related antigens, Lewis Y antigen (LeY) has not been fully investigated in non-small cell lung cancer. METHODS To assess the significance of LeY expression, 236 patients with completely resected pathologic stage 1-3a were reviewed with immunohistochemical analysis. RESULTS LeY expression was positive in 179 patients (75.8%). In poorly differentiated cancer, percentage of LeY-positive patients was lower than in moderately to well-differentiated cancer (67.2% versus 81.2%, p = 0.028). Five-year survival rate of LeY-positive patients was 78.2%, significantly higher than that of LeY-negative patients (59.7%, p = 0.001). Combined with p53 status, differences in survival proved to be marked; 5-year survival rate of patients with positive LeY expression and without aberrant p53 expression, was as high as 83.3%, whereas that of patients with negative LeY expression and with aberrant p53 expression was only 38.4% (p < 0.001). Multivariate analysis confirmed that LeY expression was a significant independent factor to predict better survival. CONCLUSIONS LeY expression is a significant prognostic factor related to grade of cancer differentiation.

Analyses of segmental lymph node metastases and intrapulmonary metastases of small lung cancer

BACKGROUND Curativity and indications for limited resection of small peripheral lung cancer remain controversial. METHODS Pathologic investigations of segmental lymph node metastases and intrapulmonary metastases in the resected lobe were performed for 94 small peripheral lung cancers (3.0 cm or less in diameter). RESULTS Nine patients had segmental lymph node metastases, 1 had intrapulmonary metastases, and 1 had both. Of these 11 patients, 5 had metastases limited to the primary tumor-bearing segments, 2 had metastases in nonprimary tumor-bearing segments, and 4 had metastases in both. Of the 10 patients with segmental lymph node metastases, 7 had metastases in both lobar-hilar and mediastinal lymph nodes, and 3 of 8 with adenocarcinoma had a tumor 2.0 cm or less. CONCLUSIONS Segmentectomy seems more favorable than wedge resection, but the risk of remnant tumor remains as compared with lobectomy. Evaluation of lobar-hilar or mediastinal lymph nodes is helpful to determine the presence or absence of segmental lymph node metastases. Limited resection can be undertaken with smaller tumors to allow preservation of more lung function while accepting a somewhat enhanced risk of recurrence.

Time trends and survival after surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC)

OBJECTIVE To evaluate the role of surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC), time trends and survival after surgery and the prognostic factors were investigated retrospectively. METHODS Consecutive patients, 155, with p-stage IIIa, pN2 NSCLC who underwent thoracotomy at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between January 1976 and December 1990 were divided into three groups by the period of operation (the earlier period: 1976-1980, n = 49; the middle period: 1981-1985, n = 55; and the later period: 1986-1990, n = 51), and were reviewed. Of the 155 patients, 84 (54.2%) were preoperatively evaluated to have mediastinal lymph nodes metastases (cN2 disease). RESULTS The 5 year survival rates in the earlier, middle and later periods were 12.1, 18.6, and 43.8%, respectively, showing significant improvement in the later period (P < 0.001, for the later period versus the earlier period or the middle period). The improvement was caused by decrease in the rate of operation-related death (4.1, 1.8, and 0.0%, in the earlier, the middle, and the later period, respectively), increase in the rate of complete tumor resection (59.1, 76.4, and 96.1%, respectively), and decrease in the ratio of pT3N2M0 patients (44.9, 34.5, and 17.6%, respectively) having poor prognosis compared with pT1-2N2M0 patients. Decrease in the ratio of cT3N2M0 patients and for increase in the rate of complete resection could be realized by accurate preoperative diagnosis with introduction of chest computed tomography (CT). Based on the preoperative evaluation, the 5 year survival rates of cT1N2M0, cT2N2M0, and cT3N2M0 patients were 39.4, 30.5, and 10.2%, respectively, showing significant poor prognosis in cT3N2M0 patients. CONCLUSION In cT1-2N2M0 or pT1-2N2M0 patients, a good prognosis can be realized by complete tumor resection with mediastinal lymph nodes dissection. In contrast, surgical treatment should not be justified in cT3N2M0 or pT3N2M0 patients.

Surgery for Thoracic Empyema Concurrent With Rupture of Lung Abscesses in a Child

The authors report surgical treatment for thoracic empyema concurrent with rupture of lung abscesses and completely collapsed lung in a child. Right middle lobectomy for ruptured abscess, debridement and closure with interrupted sutures for another abscess in the lower lobe, and decortication were performed. Positive-pressure ventilation was needed to prevent reexpansion pulmonary edema because of long-term collapsed lobes. The patient is doing well with no recurrent empyema or thoracic deformity at 3 years postoperation.

Extended radical resection for bulky N2 small cell lung carcinoma

In three patients with bulky N2 small cell lung carcinomas who received chemotherapy, complete clinical remission at the N2 site was obtained. Extended radical resection including mediastinal lymph node dissection was performed on these three patients, followed by postoperative chemotherapy. Combined resected organs were azygos vein, superior caval vein, and left atrium. We obtained good results with the patients surviving 104, 53, and 38 months respectively, after the initial therapy.