C. Frederick Kittle

Preoperative chemotherapy and irradiation for stage III non-small cell lung cancer

Surgical therapy for stage III non-small cell lung cancer (NSCLC) has not resulted in substantial long-term survival. Neoadjuvant treatment programs that could down-stage the tumor and achieve increased long-term survival would be of obvious benefit. We have used preoperative simultaneous chemotherapy and irradiation in 85 patients with clinical stage III non-small cell lung cancer considered candidates for surgical resection. One group of 56 patients was treated with cisplatin, 5-fluorouracil, and simultaneous irradiation for five days every other week for a total of four cycles. After treatment, 39 patients underwent resection, and the operative mortality was 2 (5%) of 39. A second trial was undertaken in which etoposide (VP-16) was added because of its synergism with cisplatin. In this group, 29 patients were considered to have potentially resectable disease, and 23 underwent thoracotomy with 1 operative death (4%). Of the total of 62 patients having thoracotomy, 60 underwent resection (97%). Complications were major, and there were four bronchopleural fistulas. For the 85 patients eligible for surgical intervention in these two groups of patients, the Kaplan-Meier median survival estimate is 40% at 3 years. The median survival of the 62 patients having thoracotomy is 36.6 months. Combination preoperative chemotherapy and irradiation is feasible with acceptable toxicity and operative mortality in patients with clinical stage III non-small cell lung cancer. Prospective randomized studies are suggested for further evaluation of this treatment program.

Segmental Resection for Bronchogenic Carcinoma

Segmental resection was performed on 168 patients with peripheral, Stage I bronchogenic carcinoma from 1957 to July 1, 1978. Seventy-four patients (44%) had adenocarcinoma, 58 (34%) had an epidermoid type, 28 (17%) had an unadifferentiated tumor, and 8 (5%) had a bronchoalveolar variety. Ninety-five resections were done on the left lung, the most frequent procedure being removal of the superior division of the left upper lobe (38 patients). On the right side, 73 resections were done. The anterior segment was removed most frequently (19 patients). There were 3 surgical deaths, for a mortality of less than 2%. Complications requiring prolonged hospitalization were associated with air leak in 10 (6%) of the 168 patients. Survival by actuarial curve is 53% at 5 years, 33% at 10 years, and 25% at 15 years. Forty-five patients (27%) died of metastatic carcinoma. Patients with epidermoid lesions have the most favorable prognosis.

Simultaneous Cisplatin Fluorouracil Infusion and Radiation Followed by Surgical Resection in Regionally Localized Stage III, Non–Small Cell Lung Cancer

Sixty-four patients with stage III (M omicron) non-small cell lung cancer were treated with cisplatin fluorouracil infusion chemotherapy and simultaneous radiation therapy for 5 days every other week. A total of 4 cycles (40 Gy) was followed by attempted surgical resection. Clinical response to the preoperative treatment included 5 (8%) complete and 32 (48%) partial responses. Thirty-nine (61%) underwent the planned operation, and in 9 (23%) of these patients the resected specimens were histologically negative. Clinical assessment failed to predict histological response. With 17 months median follow-up (range, 2.4-29 months), estimated 1-year survival was 61% and median survival was 16 months for all patients.

Extrapleural Pneumonectomy for Diffuse, Malignant Mesothelioma

Extrapleural pneumonectomy for malignant mesothelioma is a radical procedure that entails en bloc removal of the parietal pleura, lung, pericardium, and diaphragm. Minimal tumor remains after this procedure; palliation and occasional long-term survival may be achieved in properly selected patients. Extrapleural pneumonectomy for diffuse, malignant mesothelioma was done in 33 patients (27 male and 6 female) with 18 procedures on the left side and 15 on the right. There was a history of exposure to asbestos in 16 (48%) of the patients. Histological classification revealed that 20 tumors were epithelial, 10 were mixed, and 3 were sarcomatous. Good palliation, defined as survival for 24 months with a return to fairly normal activities, was obtained in 8 patients (24%) and survival for 36 months was achieved in 5 patients. Three patients died of the disease at 59 months, 60 months, and 82 months. There were 3 operative deaths (9.1%), and serious postoperative complications occurred in 8 patients (24%). Postoperative adjunctive therapy consisting of chemotherapy or irradiation or both was given to approximately one-half of the patients. These findings indicate that extrapleural pneumonectomy for malignant mesothelioma can be done with an acceptable morbidity and mortality. Palliation is achieved in 24% of patients, and there may be an occasional long-term survivor.

Bronchopleural fistula after stapled closure of bronchus

The incidence of bronchopleural fistula after stapling among 2,243 pulmonary resections at the Rush-Presbyterian-St. Lukes Medical Center has been reviewed. There were 35 fistulas in 1,773 stapled and in 470 sutured bronchi (segmentectomy, 2; lobectomy, 1; bilobectomy, 9; and pneumonectomy, 23). We have found that the stapler is expedient and simple to use, and that it produces a hermetic and uniform closure. The stapler is contraindicated when the bronchus is thickened, inflamed, or of insufficient length. The overall incidence of bronchopleural fistula was 1.6%. Approximately two thirds of the patients with bronchopleural fistula had preoperative radiation therapy or chemotherapy or both.

Results of Sleeve Lobectomy for Bronchogenic Carcinoma in 101 Patients

Sleeve lobectomy for bronchogenic carcinoma is an alternative to pneumonectomy. The extent and location of the tumor must be such that a sleeve procedure is feasible. The conservation of lung tissue benefits both compromised and uncompromised patients. From 1961 to 1982, 101 patients underwent sleeve lobectomy for bronchogenic carcinoma of the lung. There were 58 procedures on the right side and 43 on the left. Life-table analysis of 94 of the patients shows a 5-year survival of 30% and a 10-year survival of 22%. Preoperative irradiation was utilized in 51 patients with a 5- and 10-year survival of 25% and 16%, respectively. The sleeve lobectomy group that did not have radiation therapy demonstrated a 5-year survival of 36% and a 10-year survival of 28%. There were 2 operative deaths (2%). Completion pneumonectomy was required in 7 patients because of anastomotic dehiscence in the early postoperative period in 6 and tumor at the margin in 1. Other major complications included empyema and granulation tissue at the anastomosis that were successfully managed by bronchoscopic dilation and suture removal. Tumor recurred locally in the area of the anastomosis in 9 patients. Sleeve lobectomy is a safe procedure and when technically feasible can be considered the procedure of choice for bronchogenic carcinoma.

Pulmonary Venoocclusive Disease

Pulmonary venoocclusive disease has been established as a definite clinical entity characterized by congestive cardiac failure with pulmonary arterial hypertension, chronic interstitial pulmonary edema, and normal wedge pressure on cardiac catheterization. This disease was diagnosed and confirmed in a patient during life. A review of the 32 patients reported earlier has been done in an attempt to fine possible etiological agents. Early recognition and treatment with anticoagulants, methylprednisolone, aspirin, and dipyridamole may improve the prognosis.

Surgical Management of Malignant Mesothelioma

The surgical management of 18 patients diagnosed as having malignant mesothelioma is reviewed. Of these patients, 7 received limited treatment--pleurectomy or biopsy. The mean survival was 10 months, and no patient was disease-free at time of death. The other 11 patients were treated by radical extrapleural pneumonectomy. There were 2 long-term, disease-free survivors at 2 and 4 years. Mean survival for the entire group was 15 months, but most patients received good palliation following tumor removal. Surgical procedures for removal of malignant mesothelioma can be accomplished safely and without major morbidity. When possible, radical extrapleural pneumonectomy affords the best palliation and the only opportunity for cure.

Pre-treatment prognostic factors in stage III non-small cell lung cancer patients receiving combined modality treatment

Approximately one-third of non-small cell lung cancer (NSCLC) patients present with locally advanced disease. Increasing numbers of clinical trials are being conducted in this group of patients and recently a new international staging system has been introduced, resulting in the sub-division of Stage III into IIIa (potentially operable disease) and IIIb (inoperable disease). Kaplan-Meier survival analyses and Cox regression analyses were used to analyze data from 129 Stage III NSCLC patients who had been treated on two consecutive Phase II trials testing combined modality treatment. The pretreatment characteristics of these patients were: median age--59 years, males/females--87/42, caucasian/non-caucasian--111/18, squamous cell or adenocarcinoma/large cell carcinoma--57/72, previous weight loss less than or equal to 5%/greater than 5%-76/46, previous history of cardiorespiratory disease--no/yes--91/36, performance status (PS) 0-1/2-3--102/27, Stage III, 2 groups--IIIa/IIIb--83/46, Stage III, 3 groups--IIIa T3 N0/IIIa N2/IIIb--41/41/47, surgical eligibility--eligible/ineligible--83/46. Kaplan-Meier statistics revealed significantly longer survival for PS 0-1 versus 2-3 (p = .001), for eligible versus ineligible for surgery (p = .003), for Stage-IIIa versus IIIb (p = .004), and for Stage-IIIa T3N0 versus IIIa N2 versus IIIb (p = .004). The best model developed from Cox regression analyses included stage (IIIa T3 N0 vs IIIa N2 vs IIIb), PS, and sex. These observations appear to have implications for clinical research in Stage III NSCLC.

Intrathoracic tumors of the vagus nerve

Two patients had resection of a middle mediastinal neurilemmoma of the vagus nerve. Twenty-seven other neurogenic tumors of the intrathoracic vagus are reviewed. These tumors are generally asymptomatic except for hoarseness in an occasional patient.