Junzo Shimizu

AGGRESSIVE SURGICAL INTERVENTION IN N2 NON-SMALL CELL CANCER OF THE LUNG

An aggressive attitude toward surgical treatment was taken in patients with N2 non-small cell lung cancer in the past 10 years. Computed tomographic scanning was employed in the diagnosis of N2 disease, and had a true-positive rate of 57%. Among patients with N2 disease detected by computed tomographic scanning, surgical intervention was attempted except for those with unresectable disease. Of 190 patients with clinical N2 disease, 115 underwent surgical exploration: 9 patients had only an exploratory thoracotomy, 53 patients underwent a curative operation, and 53 had a noncurative operation. The overall 5-year survival rate of these patients was 16% and that of curatively resected patients was 20%. There were 47 patients whose N2 disease was not recognized before operation. The 5-year survival rate of this group was 20% overall and 33% in curatively resected cases. The overall 5-year survival rate of patients with N2 disease who underwent resection (106 with clinical N2 disease and 47 with clinically unrecognized N2 disease) was 17%, and that of the 84 patients undergoing curative operations was 24%. An aggressive attitude toward surgical intervention can be advocated for patients with N2 disease on the basis of our present results.

Extent of mediastinal node metastasis in clinical stage I non-small-cell lung cancer: The role of systematic nodal dissection

OBJECTIVEnTo determine the extent of lymph node metastasis in clinical stage I non-small-cell lung cancer (NSCLC).nnnMETHODSnWe performed a retrospective review of 524 patients with clinical stage I NSCLC who underwent lobectomy with systematic nodal dissection.nnnRESULTSnThe nodal status was N0 in 409 patients (78%), N1 in 44 (8%), N2 in 67 (13%), and N3 in four (0.8%). Thirty-six patients had single-level mediastinal nodal metastases and 35 had multi-level metastases. The incidence of N2/3 disease in patients with adenocarcinoma/squamous cell carcinoma/other histologic types according to tumor size was 0/0/0%, respectively, in tumors < or = 10 mm in diameter, 12/0/0% in tumors 11-20 mm in diameter, 14/4/23% in tumors 21-30 mm in diameter, and 26/14/20% in tumors >30 mm in diameter. Nodal metastases to the upper mediastinum from middle or lower lobe lesions were frequently observed in 51 N2 adenocarcinomas, whereas those to the lower mediastinum from upper lobe lesions were rare. Of 10 N2 squamous cell carcinomas, seven had regional and three had non-regional nodal metastases. The 5-year survival rate was 68, 43, and 30% in N0, N1, and N2, respectively (P<0.01, N0 versus N1, N0 and N2).nnnCONCLUSIONSnSystematic mediastinal nodal dissection should be routinely performed for clinical stage I lung cancer to ensure the correct nodal status, but it might be dispensable in the patients with peripheral squamous cell carcinoma < or = 20 mm in diameter, with central squamous cell carcinoma < or = 30 mm, and with adenocarcinoma < or = 10 mm. When systematic nodal dissection cannot be performed, the incidence and extent of nodal metastases should be taken account with respect to histologic type, size, and location of the tumor.

Results in 104 patients undergoing bronchoplastic procedures for bronchial lesions

Bronchoplastic procedures were used in 104 patients with various bronchial disorders. Ten had benign lesions and 94, malignant tumors. The principal operative procedures were sleeve lobectomy and sleeve pneumonectomy for bronchogenic carcinoma, but 11 limited bronchial resections were performed in patients with benign lesions, minute bronchogenic carcinomas, and low-grade malignant tumors. Of the 94 patients with malignant tumors, 79 underwent a bronchoplastic procedure without carinal resection (sleeve lobectomy in 75 and limited bronchial resection in 4), and there was one operative death (1.3%). The overall 5-year survival rate for the patients with bronchogenic carcinoma in this group was 45% and that for patients undergoing curative resection, 57% (survival of patients in stages I, II, and IIIA was 79%, 55%, and 30%, respectively). A bronchoplastic procedure with carinal resection was performed in 15 patients. Twelve in this group underwent sleeve pneumonectomy. There were two operative deaths, and 1 patient has survived for longer than 4 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and are still alive. We believe that bronchoplasty is a safe and valuable procedure and that limited bronchial resection appears to be the procedure of choice for localized bronchial lesions.

Second Surgical Intervention for Recurrent and Second Primary Bronchogenic Carcinomas

Second operations were performed in 1961–1990 on 23 patients with non-small cell bron-chogenic carcinoma, constituting 2.5% of 906 who had undergone pulmonary resection for such tumor and 3.6% of the 641 with apparently curative surgery. The second operation was performed for recurrent tumor in 15 cases and for second primary tumor in eight. Five-year survival after the first operation was 30% in the former group and 88% in the latter (significant difference). Among the total 23 patients, this survival rate was 51%. The study indicates that an aggressive attitude to second surgical intervention is warranted. For early detection of second lesions, follow-up at maximally 6-month intervals should be continued for more than 5 years after the first operation.

Comparison of pleuropneumonectomy and limited surgery for lung cancer with pleural dissemination

The role of surgery in the management of lung cancer with pleural dissemination is controversial. We performed a retrospective analysis of our patients with lung cancer and pleural dissemination who were treated surgically. Between 1973 and 1993, 1,206 patients with lung cancer underwent pulmonary resection at Kanazawa University Hospital. Among them, 40 (3.3%) had pleural dissemination without pleural effusion. The 1‐, 3‐, and 5‐year survival rates for 38 patients (except 2 patients undergoing exploratory thoracotomy alone) were 51.5%, 19.4%, and 19.4%, respectively. The 1‐year survival rate in the 10 patients who underwent pleuropneumonectomy was only 20%, and 9 of these patients died within 18 months postoperatively (1 patient has survived for 25 months). In contrast, the 1‐, 3‐, and 5‐year survival rates for the 14 patients who underwent resection of the primary tumor plus parietal pleurectomy were 85.1%, 35.5%, and 35.5%, respectively, a significantly better outcome (P < 0.01). Seven patients are still alive (the longest survival time is 65 months with the disease). The average survival time in the seven fatal cases was 18 months. In patients with lung cancer accompanied by pleural dissemination, it is quite possible that local excision plus pleurectomy will be justified.

Treatment of Bronchial Stricture Due to Endobronchial Tuberculosis

Abstract. Between 1974 and 1995 we encountered 19 cases of bronchial stricture or obliteration caused by endobronchial tuberculous lesions. In 11 the involvements were located at the right bronchus (including involvements of segmental and middle lobe bronchi) and in 8 at the left bronchus. On bronchoscopic biopsy of the stenosed bronchus, 7 patients showed histopathologic findings of tuberculous bronchitis, but 12 patients showed nonspecific inflammatory granular tissue. Five patients were kept under conservative observation because of mild subjective symptoms or refusal to undergo operation. Two patients underwent stent procedures but had poor outcomes. Twelve patients underwent operation. As the bronchial lesions in four of them were confined to the lobar or segmental bronchus, lobectomy was performed. One patient with a history of infantile tuberculosis had developed complete obliteration of the left main bronchus and cystic bronchiectasis in the entire lung parenchyma; pneumonectomy was essential. Seven patients who had strictures involving the main bronchus underwent bronchoplastic surgery with right (n= 4) or left (n= 3) upper sleevennlobectomy. None of the patients treated surgically showed anynnpostoperative complication or recurrence of the tuberculosis. Thesennsurgical results for endobronchial tuberculosis indicate the need fornnearly detection and operation. Bronchoscopy and computed tomography arennthe methods of choice for accurate diagnosis of bronchial involvementnnand assessment of the surgical indications. It is emphasized thatnnbronchoplastic surgery is the best treatment for bronchial stricturenninvolving bilateral main bronchi.

Clinicopathological and biological assessment of lung cancers with pleural dissemination

BACKGROUNDnThis study provides the surgical outcome of lung cancer patients with pleural dissemination, with the assessment of the clinicopathological and biological prognostic factors.nnnMETHODSnForty-three patients who underwent operations were studied. Vascular endothelial growth factor (VEGF) and autocrine motility factor receptor (AMFR/gp78) expression was immunohistochemically evaluated.nnnRESULTSnIn total, the overall 3 and 5-year survival rates were 31.4% and 13.1%, respectively. The patients who underwent the pleuropneumonectomy had a worse outcome than those who underwent limited operations (pleurectomy plus parenchymal resections were less than pneumonectomy). VEGF and AMFR/gp78 were highly expressed in primary tumors. Among the patients who underwent limited operations, pathological types other than adenocarcinoma and high expression of VEGF were significantly associated with a worse outcome. The pathological type was the only characteristic to retain a significant independent prognostic impact on overall survival.nnnCONCLUSIONSnThe results imply the validation of limited operation for lung cancer with pleural dissemination for the local control. High frequency of VEGF and AMFR/gp78 expression conform to the interpretation that patients with pleural dissemination have a high-risk of systemic disease.

Reappraisal of Bronchial Arterial Infusion Therapy for Advanced Lung Cancer

As preoperative adjuvant therapy for advanced lung cancer, bronchial arterial infusion (BAI) of a chemotherapeutic agent was administered to patients with stage IIIa and IIIb hilar lung cancer. The infusion modality was changed for each term, from a single drug infusion, to a two drug infusion and then a three drug infusion, and the combination of infused drugs was selected in accordance with cell types. A significant radiographic shrinkage was observed after BAI therapy by the single, two and three drug infusions, being noted as 40.7 per cent, 61.8 per cent and 83.9 per cent, respectively. The effect on squamous cell carcinoma was more prominent than on other cell types. Upon microscopic examination of the resected specimens, significant histo-pathological effects were observed in 57.7 per cent of the patients who received single or two drug infusions, while the rate increased to as high as 92.2 per cent in the patients who received the three drug infusion. The histological effects of BAI therapy were also most marked in squamous cell carcinoma. It is of special interest that 5 of the 10 patients who received the three drug infusion of Carboquone (CQ)+ Mitomycin C (MMC)+Nimustine-HCL (ACNU) for squamous cell carcinoma, showed complete disappearance of viable cancer cells at the tumor site; something which was never observed after the single and two drug infusions. It was therefore concluded that BAI therapy for advanced lung cancer should be reappraised through the modification of infusion methods.

Treatment of multiple primary squamous cell carcinomas of the lung

BACKGROUNDnThe prevalence of multiple primary bronchogenic cancers, especially squamous cell carcinoma, has been increasing as a result of improvements in early detection and cancer therapy.nnnMATERIALSnWe treated 14 patients with multiple squamous cell carcinoma of the tracheobronchial tree and lung, which corresponded to 2.3% of all squamous cell carcinoma patients undergoing resection.nnnRESULTSnTwo patients had peripheral secondary tumors and underwent segmentectomy or partial resection of the lung with good results. The secondary lesions were superficial and minute (less than 5 mm) in 3 patients, and treated with neodymium-yttrium aluminum garnet laser ablation. Five patients had endobronchial tumors of the nodular or polypoid type with suspected deep invasion or invasion extending beyond the bronchial wall based on the bronchoscopic findings. They underwent parenchymal-sparing limited bronchoplasty with excellent results. Three patients had more advanced tumor with massive invasion outside the bronchial wall without lymph node metastases, 1 patient underwent sleeve lobectomy with long survival, and the other 2 patients without operation died of bleeding or had recurrence. One patient with stage IIIA (T2 N2) secondary cancer who underwent lobectomy died 14 months after the second operation.nnnCONCLUSIONSnThe surgical treatment of multiple squamous cell carcinoma is justified and limited operation using bronchoplastic techniques provides superior results.

Demonstration of nucleolar organizer regions in lung carcinoma by silver staining

Nucleolar organizer regions (NORs) were investigated in lung carcinomas by silver staining. This method was applied to 111 lung carcinoma specimens, including 40 with squamous cell carcinoma (SCC), 42 with adenocarcinoma (ADENO), 8 with adenosquamous carcinoma (ADESQ), 8 with small cell carcinoma (SMCC), 6 with large cell carcinoma (LGCC), and 7 with typical carcinoid tumors (CAOID). The mean AgNOR counts of ADENO, SCC, ADESQ, SMCC, and LGCC were significantly higher than those of the normal bronchial surface and those of the glandular or alveolar epithelium. The mean AgNOR count of CAOID was significantly higher than those of the normal glandular and alveolar epithelium but not that of the surface epithelium. The mean AgNOR count of SCC was significantly higher than that of bronchial squamous metaplasia, and the count of SMCC was significantly higher than that of CAOID. Within the same cancer category, the mean number of AgNORs increased in parallel with the histological tumor grades. These results indicate that the AgNOR method is useful for differentiating lung carcinoma from its normal counterparts and for evaluating histological tumor grades in the same lineage of lung carcinoma.