The history of lobectomy and segmentectomy including sleeve resection.

The evolution of pulmonary lobectomy during the past six centuries is presented. The anesthetic problems of an open thorax, the absence of antibiotics, and the absence of radiology initially complicated thoracic surgery. Surgical pioneers differed strongly on the best techniques for lobectomy. Concurrence in their opinions evolved by the formation of a specialty group, meetings, and journals. The recent techniques of segmentectomy and sleeve resection provide further refinement of pulmonary resections.

Combined modality therapy for stage III non-small cell lung carcinoma: results of treatment and patterns of failure.

Patients with Stage III non-small cell lung carcinoma continue to pose a therapeutic problem with dismal cure rates. In an effort to improve on these results, 129 patients with biopsy-proven clinical Stage III non-small cell lung carcinoma from November 1982 through November 1987, were entered into two consecutive Phase II studies at Rush-Presbyterian-St. Luke's Medical Center. Treatment in the first study consisted of Cisplatin and 5-Fluorouracil infusion with concomitant split course radiation; in the second Etoposide was added. Radiation and chemotherapy were given simultaneously on days one through five of each cycle in a preoperative fashion for four cycles in patients considered eligible for surgery and in a definitive fashion for six cycles in patients considered ineligible for surgery. Radiation was given in 2 Gy fractions for a planned preoperative dose of 40 Gy and a definitive dose of 60 Gy. Surgical resection was attempted four to five weeks later in patients treated preoperatively. Thus, 83 patients were treated preoperatively and 46 definitively. Eighty-three patients (64%) had IIIA disease and IIIB disease was found in the remainder of the patients. Sixty-two patients (75%) in the eligible for surgery group had a thoracotomy after the combined treatment with a resectability rate of 97% and an operative mortality rate of 5%. There were 17 patients (27%) with no evidence of residual cancer in the resected specimen. Three-year survival for the eligible for surgery group at 40% was significantly better than 19% observed in the ineligible for surgery group (p = 0.003). Seventy-six percent of the patients with no residual cancer in the resected specimen are recurrence-free at three years compared to 34% of the patients with gross residual. A total of 81 patients have failed after their treatment; 49 (59%) in the eligible for surgery group and 32 (70%) in the ineligible for surgery group. Of all the patients who failed, local failure alone and as a component occurred in 21 (26%) and 36 (44%) patients, respectively. Failure in distant sites alone was noted in 56% of the overall failures. Severe toxicity was unusual. There were three treatment related deaths (2%). Radiation esophagitis and pneumonitis were only mild to moderate seen in less than 10% of the patients. Survival rates and patterns of failure according to the stage of the disease, histology, treatment group and pathologic response will be presented in detail.

Bronchopleural fistula after stapled closure of bronchus.

The incidence of bronchopleural fistula after stapling among 2,243 pulmonary resections at the Rush-Presbyterian-St. Luke's 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.

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.

Combined modality therapy for locally advanced non-small cell lung carcinoma.

Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting.

Surgical management of pulmonary metastatic leiomyosarcoma with gross endobronchial extension.

Metastatic leiomyosarcoma occasionally is seen with gross endobronchial extension without invasion of the bronchial wall. These patients have major airway obstruction and partial or total atelectasis of the lung. Precise bronchoscopic assessment coupled with intraoperative bronchotomy allows the surgeon to determine the origin of the tumor and to save uninvolved pulmonary parenchyma. Our experience with 4 such patients illustrates the possibility of saving lung tissue despite total bronchial obstruction.

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.

Surgical treatment of primary lung cancer and solitary intracranial metastasis.

From 1976 through 1986, 12 patients underwent 14 thoracotomies (two patients had a second thoracotomy for recurrence) and 16 craniotomies (two patients had three craniotomies for recurrence) for carcinoma of the lung and solitary intracranial metastasis. Age ranged from 40 to 65 years. Adjuvant therapy (chemotherapy and thoracic irradiation) was employed in three patients prior to thoracotomy and in four patients following thoracotomy. Whole-brain irradiation was used in four patients after craniotomy. Improvement in neurologic symptoms following craniotomy was noted in 15 of 16 instances. There were no operative mortalities. Overall survival from the time of initial diagnosis ranged from 13 to 63 months. Survival following initial craniotomy ranged from 12 to 56 months. Eight patients are currently alive and well with no disabling neurological symptoms. These results support an aggressive approach to the resection of solitary brain metastasis from bronchogenic carcinoma, both for palliation and prolongation of survival.

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.

Preoperative combined modality therapy for stage III M0 non-small cell lung carcinoma.

More than 1/3 of all non-small cell lung carcinoma (NSCLC) patients present with locally advanced non-metastatic disease. Despite radiation therapy and surgery the survival of these patients remains poor. In an effort to improve upon these results 33 clinical Stage III M0 patients from April 1985 through September 1986 were entered into a Phase II study at Rush-Presbyterian-St. Luke's Medical Center. Treatment included 5-FU by continuous infusion, VP-16, cisplatin and concurrent split course radiation therapy followed by surgical resection when possible. The overall clinical response rate is 74%. Fifty-seven percent of the preoperative group of patients went to surgery with a 100% resectability rate. These patients had a 50% pathologic complete response with no tumor found in the resected specimen. All surgical margins were free of disease and there were no operative deaths. This concurrent combined modality therapy is feasible with the major toxicities being leukopenia, nausea, and vomiting. With an overall median follow-up of 15 months, 36% of the patients remain alive. Overall local control is 71%. Actuarial observed 2 yr. survival is 33% and the median survival is 15 months. Histologic complete response appears to be an early indicator of the efficacy of this treatment regime. With 83% of the resected pathologic complete responders alive without evidence of disease, this preoperative combined modality therapy offers an appealing approach.

Phase II trial of therapy with etoposide, 5-fluorouracil by continuous infusion, cisplatin, and simultaneous split-course radiation in stage III non-small cell bronchogenic carcinoma.

Survival of patients who have clinical stage IIIM0 non-small cell bronchogenic carcinoma remains relatively short despite treatment with either surgery or radiation. Results from a phase II study of simultaneous continuous infusion of 5-fluorouracil, cisplatin, and split-course radiation with or without surgery indicate that median survival duration in patients treated with this combined modality approach may be better than the median survival for patients treated with radiation alone. Etoposide has been added to this regimen, and 32 stage IIIM0 non-small cell lung cancer patients have been treated with the 3-drug regimen resulting in a 73% clinical partial remission rate. No residual tumor was found in 6 of 12 patients who had pulmonary resection after 4 courses of chemotherapy and radiation. The sites of failure in 8 patients with recurrent disease are as follows: local only, 3; distant only, 4; and local and distant, 1. The major toxicities have been leukopenia, nausea, and vomiting. The median leukocyte nadir was 2,400/mm3. A leukocyte count less than 1,000/mm3 was observed in 2 patients (7%), 1 of whom died of progressive pneumonia. All patients experienced nausea, vomiting, and anorexia. Severe esophagitis, dermatitis, and pneumonitis were not observed. Survival analysis has not been done because median follow-up time (326 days) is relatively short.

Tuberculous esophagitis with aortic aneurysm fistula.

A patient with treated pulmonary tuberculosis and a thoracic aortic aneurysm was seen with a one-month history of dysphagia. Barium swallow revealed a mass in the lower esophagus and extravasation of contrast material into the mediastinum. Endoscopy and biopsy specimens showed acid-fast organisms. The patient was treated with antituberculous drug therapy but bled massively from the gastrointestinal tract and died. Autopsy revealed an aortoesophageal fistula at the level of the thoracic aneurysm. Histopathological study confirmed that this rare tuberculous lesion of the esophagus caused the fistula.

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.

Sleeve lobectomy for bronchogenic carcinoma: the Rush-Presbyterian-St. Luke's Medical Center experience.

One hundred and fifteen various types of sleeve lobectomy procedures were performed from 1961 to June 1985 with a perioperative mortality of 1.7%. Six of the eight patients who required completion procedures were considered as technical failures, a failure rate of 5%. Cumulative survival is 33% at five years and 22% at ten years.

Pulmonary resection in patients after pneumonectomy.

In 15 patients with a previous pneumonectomy (eight on the right and seven on the left), a new "lesion" developed in the remaining lung. Fourteen had the pneumonectomy for carcinoma (13 men and 1 woman), and 1 woman had a pneumonectomy for blastomycosis. At the second operation (4 months to 16 years after the pneumonectomy), limited resection of a primary or metastatic malignancy was done. The excision ranged from lobectomy to multiple wedges. One patient died on the sixth postoperative day, presumably a cardiac death. Eight patients died 2 to 33 months postoperatively. Six patients are now living: 3 have no evidence of disease (18, 35, and 70 months), and 3 have recurrent disease (26, 41, and 73 months). There is evidence that pulmonary resection after pneumonectomy is feasible with a low operative mortality and that resection of these "secondary" tumors can result in prolonged, worthwhile survival.

Neuroendocrine neoplasms of the bronchopulmonary tract. A classification of the spectrum of carcinoid to small cell carcinoma and intervening variants.

Eighty-one primary pulmonary neuroendocrine neoplasms were assessed by the classification of Gould and associates. The neuroendocrine features of these tumors were studied by a combination of conventional light microscopy, electron microscopy, and immunohistochemical staining for hormonal substances and neuron-specific enolase. In each case, clinical follow-up was obtained to test the prognostic value of this new pathological classification. This study indicated that bronchial carcinoids are very low-grade neuroendocrine neoplasms that are locally invasive and only occasionally metastasize late in their course. Well-differentiated neuroendocrine carcinomas are relatively low-grade carcinomas that either present with or subsequently develop nodal or distant metastases in 73% of patients. Intermediate cell neuroendocrine carcinomas are highly aggressive tumors often mistakenly called "large cell undifferentiated carcinoma." Their clinical course is comparable to that of small cell neuroendocrine carcinomas, which has a mean survival of 9 months. The different clinical courses of these tumors demonstrate the predictive value of the proposed classification. It appears particularly valuable to identify well-differentiated neuroendocrine carcinoma as a low-grade carcinoma, distinct from true bronchial carcinoids. This classification may resolve some discrepancies regarding the therapy for and prognosis of "carcinoids" and their presumed variants.