Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice.

BACKGROUND: Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care. METHODS: We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping. RESULTS: Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and ß-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy. CONCLUSIONS: Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.

Preoperative chemotherapy followed by surgery with possible postoperative radiotherapy in squamous cell carcinoma of the esophagus: evaluation of the chemotherapy component.

Twenty-four patients with squamous cell cancer of the esophagus were entered into a treatment protocol consisting of preoperative chemotherapy (CT), surgical resection (SR), and possible postoperative CT or radiation therapy (RT) beginning August 1981. CT consisted of two cycles of 5-fluorouracil, 1,000 mg/m2, by continuous intravenous infusion for 4 days and cisplatin, 100 mg/m2, on day 4 with mannitol-induced diuresis at 4-week intervals. Postoperatively, RT was administered when resection margins were minimal or if paraesophageal nodes were abnormal; the RT consisted of 5,000 to 5,400 cGy to the tumor area plus a 800- to 1,200-cGy boost to known abnormal tumor margins. Nineteen of 24 patients were resectable (79%). There was one SR death (5%). One of 22 had a normal barium swallow post-CT, no visible tumor at SR, and no pathologic evidence of any residual disease. There was complete radiologic and gross clinical disappearance of tumor post-CT or post-SR in ten of 22 patients (45%). Four of 22 (18%) had greater than or equal to 50% regression, and five of 22 (23%) had no response. Toxicity of CT was mild. Eight of 19 patients (42%) received RT, and six of 19 (32%) received CT postoperatively. Sixteen of 24 (67%) are alive with a median duration of observation of 9.5 months. Eight of 24 (33%) are dead, five of whom had not responded to preoperative CT. Ten of 14 responders are alive and disease free. The mean survival time for nonresponders was 6.70 months and for responders, 20.40 months, with the longest survivor disease free at 45 months.

Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage IIIA non-small-cell carcinoma of the lung: report of a Cancer and Leukemia Group B phase II study.

PURPOSE: This phase II trial was designed to evaluate the feasibility, toxicity, response rates, and survival for neoadjuvant chemotherapy and radiotherapy (RT) followed by surgical resection in newly diagnosed patients with surgically staged IIIA non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Previously untreated patients with NSCLC underwent bronchoscopy, chest and abdominal computed tomography (CT), bone scan, and surgical staging of the mediastinum. Neoadjuvant treatment consisted of concurrent chemotherapy and RT. Patients then underwent surgical resection, which was followed in turn by additional chemotherapy and RT. Chemotherapy included cisplatin 100 mg/m2 on days 1 and 29, vinblastine 3 mg/m2 on days 1 and 3 and 29 and 31, and fluorouracil (5-FU) 30 mg/kg/d by infusion on days 1 to 3 and 29 to 31 (FVP). RT began on day 1 and included 3,000 cGy in 15 fractions. Surgery took place on day 55, and one more cycle of chemotherapy and an additional 3,000 cGy of RT began on day 85. RESULTS: Forty-one eligible patients (median follow-up, 53 months) were studied. N2 disease was present in 80%, whereas 20% had T3N0 or T3N1 lesions. Response to neoadjuvant chemotherapy and RT included no complete responses (CR), 21 (51%) partial responses (PR) or regressions, 19 (46%) stable disease (SD), and one (2%) progressive disease (PD). Thirty-one patients underwent surgery, and 25 were resected. In four of the 25 resection specimens, no viable tumor was present, whereas in three of the six unresectable patients, extensive biopsy results demonstrated only necrotic tumor. The maximum response achieved using all protocol treatment was 27 (66%) CRs, seven (17%) PRs or regression, six (15%) SDs, and one (2%) PD. Toxicity was substantial and primarily hematologic. There were six (15%) treatment-related deaths, which included three perioperative deaths and three chemotherapy-related toxicity deaths. The Kaplan-Meier curve indicated a 1-year survival of 58% and a median survival of 15.5 months. Nine patients (22%) remain disease-free. CONCLUSIONS: There was a reasonably high rate of PR associated with concurrent neoadjuvant chemotherapy and RT, and a high percentage of patients who ultimately were rendered completely disease-free. However, treatment-related morbidity and mortality was common. Median survival seemed to be only modestly improved beyond that achieved with less intensive means of treatment. However, a group has emerged of patients who enjoy prolonged disease-free survival and possible cure.

Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study.

PURPOSE: With the conventional approach of surgery and postoperative radiotherapy for patients with Masaoka Stage III thymoma, progress has been slow for an improvement in the long-term survival rate over the past 20 years. The objective of this study was to evaluate the pattern of failure and survival after surgery and postoperative radiotherapy in Stage III thymoma and search for a new direction for better therapy outcome. METHODS AND MATERIALS: Between 1975 and 1993, 111 patients with thymoma were treated at Massachusetts General Hospital. Of these, 32 patients were determined to have Masaoka Stage III thymoma. The initial treatment included surgery for clinically resectable disease in 25 patients and preoperative therapy for unresectable disease in 7 patients. Surgical procedure consisted of thymectomy plus resection of involved tissues. For postoperative radiotherapy (n = 23), radiation dose consisted of 45-50 Gy for close resection margins, 54 Gy for microscopically positive resection margins, and 60 Gy for grossly positive margins administered in 1.8 to 2.0 Gy of daily dose fractions, 5 fractions a week, over a period of 5 to 6.6 weeks. In preoperative radiotherapy, a dose of 40 Gy was administered in 2.0 Gy of daily dose fractions, 5 days a week. For patients with large tumor requiring more than 30% of total lung volume included in the target volume (n = 3), a preoperative radiation dose of 30 Gy was administered and an additional dose of 24-30 Gy was given to the tumor bed region after surgery for positive resection margins. RESULTS: Patients with Stage III thymoma accounted for 29% (32/111 patients) of all patients. The median age was 57 years with a range from 27 to 81 years; gender ratio was 10:22 for male to female. The median follow-up time was 6 years. Histologic subtypes included well-differentiated thymic carcinoma in 19 (59%), high-grade carcinoma in 6 (19%), organoid thymoma in 4 (13%), and cortical thymoma in 3 (9%) according to the Marino and Müller-Hermelink classification. The overall survival rates were 71% and 54% at 5 and 10 years, respectively. Ten of the 25 patients who were subjected to surgery as initial treatment were found to have incomplete resection by histopathologic evaluation. The 5- and 10-year survival rates were 86% and 69% for patients (n = 15) with clear resection margins as compared with 28% and 14% for those (n = 10) with incomplete resection margins even after postoperative therapy, p = 0.002. Survival rates at 5 and 10 years were 100% and 67% for those with unresectable disease treated with preoperative radiation (n = 6) and subsequent surgery (n = 3). Recurrence was noted in 12 of 32 patients and 11 of these died of recurrent thymoma. Recurrences at pleura and tumor bed accounted for 77% of all relapses, and all pleural recurrences were observed among the patients who were treated with surgery initially. CONCLUSION: Incomplete resection leads to poor results even with postoperative radiotherapy or chemoradiotherapy in Stage III thymoma. Pleural recurrence is also observed more often among patients treated with surgery first. These findings suggest that preoperative radiotherapy or chemoradiotherapy may result in an increase in survival by improving the rate of complete resection and reducing local and pleural recurrences.

Carinal resection for bronchogenic carcinoma.

Techniques are available for carinal resection and reconstruction for bronchogenic carcinoma involving the carina. Successful outcome depends on careful patient selection, thorough preoperative evaluation, careful anesthetic management, strict attention to surgical technique, and compulsive postoperative care. Since 1973 we have performed 37 carinal resections for bronchogenic carcinoma: 21 right carinal pneumonectomies, 7 carinal resections, 7 carina plus lobe resections, and 2 carina plus pneumonectomy stump resections. Five patients had diseased N2 nodes and 13 patients had diseased N1 nodes. Complications included pulmonary (8), vocal cord paresis (3), atrial fibrillation (9), anastomotic stenosis (4), and anastomotic separation (3). There were 3 early postoperative deaths (8%). All were related to adult respiratory distress syndrome and were unresponsive to aggressive treatment. There were 4 late postoperative deaths between 2 and 4 months (10.9%). All late postoperative deaths were related to anastomotic complications (stenosis [1] and separation [3]). There are 5 absolute 5-year survivors and an actuarial 5-year survival rate of 19%.

Resection of pulmonary blebs and pleurodesis for spontaneous pneumothorax.

Over a 20-year period, 83 patients underwent operative pleurodesis with resection of pulmonary blebs for spontaneous pneumothorax. Follow-up for all patients was between 5 and 25 years, with a mean of 9.1 years. There were five early (5.6 percent) and three late recurrences (3.6 percent). There were no deaths or need for blood transfusion in our series. There was a low incidence of postoperative fever (n = 8), minor wound infection (n = 6), air leak (n = 6), or pneumonia (n = 2). The low morbidity and recurrence rates compare favorably with published series of alternative treatment options for spontaneous pneumothorax.

Bronchial sleeve resection with and without pulmonary resection.

Sleeve resection with and without pulmonary resection is safe, effective, and appropriate treatment for a wide range of endobronchial lesions including neoplasms of low-grade malignant potential and selected cases of bronchogenic carcinoma. Sixty-three patients underwent 64 sleeve resection procedures (47 with concomitant pulmonary resection and 17 without) at the Massachusetts General Hospital between 1962 in 1986 with a 30 day mortality rate of 4.7%. Applicability of the technique for bronchial lesions which do not require concomitant pulmonary resection is emphasized. Types of disease included a heterogeneous collection of 31 benign tumors, neoplasms of low-grade malignant potential, and bronchostenosis and 33 bronchogenic carcinomas. Actuarial disease-free survival rate for the former group was 100% at 5 years. Quality of life was excellent for this group. Five-year survival rates for bronchogenic carcinoma (24 squamous cell, seven adenocarcinoma, two undifferentiated) were 58% +/- 25% (+/- standard error), 69 +/- 18%, and 38% +/- 13% in Stages I, II, and III, respectively. The 5 year survival rate of 31% +/- 16% in 14 patients selected because of decreased respiratory reserve compared with 60% +/- 14% in 19 patients for whom sleeve was the operation of choice on the sole basis of anatomic suitability. Sleeve resection is the ideal form of excisional therapy for benign endobronchial tumors, bronchostenosis, tumors of low-grade malignant potential, and for selected cases of carcinoma.

The omentum in the management of complicated cardiothoracic problems.

The pedicled omentum finds use in cardiothoracic surgery for management of complicated problems and prevention of serious complications. Its blood supply is excellent and is capable of inducing neovascularity. Based on the right gastroepiploic artery, it reaches anywhere in the thorax or neck. Its bulk helps to fill infected spaces. Thirty-seven patients have been treated with the pedicled omentum. In 16 patients the goal was preventive, to avoid bleeding, anastomotic leakage, or infection or to provide a source of fibroplasia or neovascularity. In eight patients with cervical exenteration the flap protected against innominate artery erosion and esophageal leakage, generally in an irradiated field. In six patients it permitted primary healing of heavily irradiated trachea--formerly unlikely. It was also used to provide coverage of a chest wall prosthesis in two patients. In 21 patients the omentum was used to obtain healing in the presence of infection. Bronchopleural fistulas were successfully closed in eight of nine patients. Six mediastinal infections that developed after cardiac operations were successfully treated. Four unusual vascular infections necessitated the use of omentum. Two patients had closure of esophageal perforations buttressed with omentum. This series demonstrates the efficacy of the omentum in the management of complex cardiac, vascular, esophageal, tracheal, bronchial, pleural, and chest wall problems.

Temporary and permanent restoration of airway continuity with the tracheal T-tube.

The advantages of the tracheal T-tube compared with a regular tracheostomy tube are a physiologic direction of air flow, preservation of laryngeal phonation, and superior patient acceptance. Between 1968 and 1991, 140 patients aged 7 months to 95 years underwent placement of T-, TY- (n = 7), or a modified extended T-tube (n = 4). Primary diagnosis was postintubation stenosis in 86 patients, burn injury in 13 patients, malignant airway tumors in 12 patients, and various disorders in 29 patients. Stenting with a silicone rubber tube was temporary in 31 patients and 14 underwent later operative reconstruction. Definitive permanent insertion was performed in 49 patients. A modified tube was used in 4 patients with left main bronchial stenosis with effective long-term palliation in 3. Postoperative airway obstruction prompted placement in 32 patients. Positioning of the T-tube above the vocal cords in 12 patients for subglottic stenosis was effective in 10. The T-tube was not tolerated in 28 patients (20%) because of obstruction of the upper limb or aspiration. Five of 10 patients under the age of 10 years had airway obstruction necessitating tube removal. Long-term intubation in 112 patients exceeded 1 year in 49 patients and 5 years in 12 patients. Only 5 patients required tube removal for obstructive problems more than 2 months after placement. The tracheal T-tube restores airway patency reliably with excellent long-term results and represents the preferred management of chronic airway obstruction not amenable to surgical reconstruction.

Needle localization of peripheral lung nodules for video-assisted thoracoscopic surgery.

Video-assisted thoracoscopic surgery provides an alternative to conventional thoracotomy for resection of peripheral lung nodules. To localize small peripheral lung nodules that may not be visible or palpable by the surgeon, we have placed a Kopans hook wire percutaneously into the lung as a guide. The indications for localization included previous nondiagnostic percutaneous needle aspiration biopsy (PNAB) (n = 4), nodules too small for PNAB (n = 2), nodules inaccessible to PNAB (n = 3), and planned resection of a known peripheral tumor less than 1 cm (n = 1). The localization procedure was performed with computed tomographic guidance in all patients. The nodules ranged in size from 2 to 15 mm and were located immediately subpleural to 2-cm deep the pleura. A 20-gauge Greene biopsy needle was used as an introducer for a 35-cm-long Kopans hook wire. Patients were sent directly to the operating room in a dependent position. All ten nodules were successfully resected, including hamartoma (n = 1), carcinoid tumors (n = 2), granulomas (n = 3), adenocarcinoma (n = 1), fibrosis (n = 1), benign metastasizing leiomyoma (n = 1), and lymphoma (n = 1). In two patients, the wire slipped out of the lung. Small focal pneumothoraces developed in five patients. There were no major complications. This procedure can safely and effectively localize nonvisible or nonpalpable pulmonary nodules for thoracoscopic surgery for diagnostic purposes or for resection of small peripheral tumors in patients who cannot tolerate a lobectomy or pneumonectomy.

Postpneumonectomy bronchopleural fistula after sutured bronchial closure: incidence, risk factors, and management.

OBJECTIVE: Postpneumonectomy bronchopleural fistula remains a morbid complication after pneumonectomy. The incidence, risk factors, and management of postpneumonectomy bronchopleural fistula were evaluated in 256 consecutive patients who underwent pneumonectomy with a standardized suture closure of the bronchus. METHODS: Pneumonectomy was performed for lung cancer in 198 cases, for other malignancy in 20 cases, and for benign causes in 38 cases. The bronchial stump was closed with interrupted simple sutures to emphasize a long, membranous wall flap. All stumps were covered by autologous tissue. RESULTS: The incidence of postpneumonectomy bronchopleural fistula was 3.1%. Risk factors for bronchopleural fistula were the need for postoperative ventilation (p = 0.0001) and right pneumonectomy (p = 0.04). Five patients had bronchopleural fistulas as a result of pulmonary complications necessitating ventilation; the cause in the remaining three cases appeared to be technical. Reclosure was successful in five cases (mean postoperative day 12); in one case a pinhole fistula was healed by drainage alone. Two (25%) of the eight patients who had bronchopleural fistulas died. CONCLUSIONS: Careful, sutured closure of the main bronchus with a tissue buttress after pneumonectomy yields excellent results. The most significant risk factor for bronchopleural fistula is a pulmonary complication necessitating ventilation. Contrary to previous reports, reclosure is usually successful even if performed late.

Reoperative tracheal resection and reconstruction for unsuccessful repair of postintubation stenosis.

OBJECTIVE: Our objective was to analyze characteristics and results of redo tracheal resection and reconstruction. METHODS: Seventy-five patients were operated on between 1966 and 1997 after unsuccessful initial repairs for postintubation tracheal stenosis. RESULTS: Sixteen of these patients came from a group of 32 patients with unsuccessful repair among the 450 primary resections and reconstructions performed at our institution. Fifty-nine patients were referred to us after unsuccessful initial repair elsewhere. Initial management was a T-tube or tracheotomy in 39 patients. The length of repeat resection ranged from 1.0 cm to 5.5 cm (mean 3.5 cm). A laryngeal release was used in 19 patients (25%) to reduce anastomotic tension. Complications occurred in 29 patients (39%) and were most frequent in the group requiring laryngeal release (12/19, 63.2%). Overall outcome was good in 59 patients (78.6%) and satisfactory in 10 (13.3%). The repair was unsuccessful in four patients (5.3%), and two patients died (2.6%). CONCLUSIONS: Despite difficulties encountered in reoperative surgery after failed tracheal reconstruction for postintubation stenosis, successful outcome may be achieved in a large number of cases.

Postintubation tracheal stenosis. Treatment and results.

A total of 503 patients underwent 521 tracheal resections and reconstructions for postintubation stenosis from 1965 through 1992. Fifty-three had had prior attempts at surgical resection, 51 others had undergone various forms of tracheal or laryngeal repair, and 45 had had laser treatment. There were 251 cuff lesions, 178 stomal lesions, 38 at both levels, and 36 of indeterminate origin. Sixty-two patients with major laryngeal injuries required complete resection of anterior cricoid cartilage and anastomosis of trachea to thyroid cartilage, and 117 had tracheal anastomosis to the cricoid. A cervical approach was used in 350, cervicomediastinal in 145, and transthoracic in 8. Length of resection was 1.0 to 7.5 cm. Forty-nine had laryngeal release to reduce anastomotic tension. A total of 471 patients (93.7%) had good (87.5%) or satisfactory (6.2%) results. Eighteen of 37 whose operation failed underwent a second reconstruction. Eighteen required postoperative tracheostomy or T-tube insertion for extensive or multilevel disease. Twelve died (2.4%). The most common complication, suture line granulations (9.7%), has almost vanished with the use of absorbable sutures. Wound infection occurred in 15 (3%) and glottic dysfunction in 11 (2.2%). Five had postoperative innominate artery hemorrhage. Resection and reconstruction offer optimal treatment for postintubation tracheal stenosis.

Survival following resection for second and third primary lung cancers.

The performance of sequential resections and the consideration of new lesions as second or third primary lung cancers remain controversial issues. Criteria to define these as new primary lesions depend upon a difference in histologic types, a prolonged interval between initial and second or third resections, and location in the contralateral lung or a different ipsilateral lobe. Ninety patients have undergone multiple resections for bronchogenic carcinoma from 1960 to December, 1983. There were 10 examples of synchronous lesions and the remaining 80 were metachronous with the longest interval between resections being 17 years, 4 months. The initial surgical procedure was pneumonectomy in 11, lobectomy in 43, sleeve lobectomy in eight, segmentectomy in 27, and carinal resection in one. At the second operation, the procedures were segmentectomy in 55, lobectomy in 11, completion lobectomy in six, and completion pneumonectomy in 15. Two patients had sternotomy with bilateral resections and one patient had a tracheal resection. At the third operation, the procedures were segmentectomy in seven, completion lobectomy in two, and completion pneumonectomy in two. In 20 patients undergoing the second procedure and three undergoing a third resection, a different cell type was identified. The perioperative mortality following the second operation was seven of 90 patients (8%) and there were no deaths in those patients undergoing three resections. The cumulative survival rate following second resection in 80 patients with metachronous tumors was 33% at 5 years and 20% at 10 years. These data support continued aggressive surgical approach to second and third primary lung cancers.

Superior sulcus lung tumors. Results of combined treatment (irradiation and radical resection).

Twenty-one patients underwent combined therapy (irradiation and radical resection) for a Pancoast tumor at the Massachusetts General Hospital between 1976 and 1985. All patients underwent en bloc removal of the apical chest wall and underlying lung. In addition four patients required subclavian artery resection, and in five patients a portion of the vertebral body was resected. There were three operative deaths. Median survival was 24 months and actuarial survival rate was 55% at 3 years and 27% at 5 years. Long-term palliation of pain was achieved in 72% of the patients. Involvement of the subclavian artery, vertebral body, or rib did not preclude long-term survival. Computed tomographic scanning in these patients is often indeterminate regarding invasion of chest wall structures but is more helpful than plain films alone. When compared to recent series in which irradiation alone was used, the combined approach appears to produce better results.

Resection for bronchogenic carcinoma involving the carina: long-term results and effect of nodal status on outcome.

OBJECTIVE: Bronchogenic carcinoma in close proximity to or involving the carina remains a challenging problem for thoracic surgeons. The operative procedures to allow complete resection are technically demanding and can be associated with significant morbidity and mortality. Little is known about long-term survival data to guide therapy in these patients. METHODS: We conducted a single-institution retrospective review. RESULTS: We have performed 60 carinal resections for bronchogenic carcinoma: 18 isolated carinal resections for tumor confined to the carinal or proximal main stem bronchus; 35 carinal pneumonectomies; 5 carinal plus lobar resections, and 2 carinal resections for stump recurrence after prior pneumonectomy. Thirteen patients (22%) had a history of lung or airway surgery. The overall operative mortality was 15%, improved from the first half of the series (20%) to the second half (10%), and varied according to the type of resection performed. Adult respiratory distress syndrome was responsible for 5 early deaths, and all late deaths were related to anastomotic complications. In 34 patients, all lymph nodes were negative for metastatic disease; 15 patients had positive N1 nodes, and 11 patients had positive N2/N3 nodes. Complete follow-up was accomplished in 90%, with a mean follow-up of 59 months. The overall 5-year survival including operative mortality was 42%, with 19 absolute 5-year survivors. Survival was highest after isolated carinal resection (51%). Lymph node involvement had a strong influence on survival: patients without nodal involvement had a 5-year survival of 51%, compared with 32% for patients with N1 disease and 12% for those with N2/N3 disease. CONCLUSIONS: This constitutes one of the largest single-institution reports on carinal resection for bronchogenic carcinoma involving the carina. Morbidity and mortality rates are acceptable. The overall survival including operative mortality is 42%. Positive N2/N3 lymph nodes may be a contraindication to surgery because of poor prognosis.

Bronchopulmonary carcinoid tumors associated with Cushing's syndrome: a more aggressive variant of typical carcinoid.

OBJECTIVES: Our objectives were to delineate the clinicopathologic characteristics of adrenocorticotropin-secreting bronchopulmonary carcinoid tumors causing Cushing's syndrome and to derive from these findings a rational approach to diagnosis and surgical management of this unusual condition. METHODS: We conducted a retrospective, chart-review analysis of seven consecutive patients treated at the Massachusetts General Hospital over a 16-year period. RESULTS: The patients uniformly had symptoms of marked hypercortisolism, and the underlying lung lesions remained clinically occult for a mean of 24 months. Standard endocrine testing was misleading in 83% of patients, reinforcing the need for an alternative diagnostic strategy based on petrosal sinus catheterization and computed tomography of the chest. Although 72% of the tumors were typical carcinoids by standard criteria, 57% demonstrated microscopic evidence of local invasiveness, and 43% were associated with mediastinal lymph node metastases. Eighty-six percent of patients have been cured by pulmonary resection a mean of 59 months after the operation, but 50% of these required a second operation for resection of involved lymph nodes after an initial relapse. CONCLUSIONS: These data suggest that adrenocorticotropin-secreting bronchopulmonary carcinoid tumors represent a distinct, more aggressive subtype of the usual, typical carcinoid. The high rate of lymphatic and local spread demands a surgical approach consisting of anatomic resection and routine mediastinal lymph node dissection.

Survival and function after sleeve lobectomy for lung cancer.

Between 1962 and 1991, 72 patients (mean age 63.4 years) underwent sleeve lobectomy for primary lung cancer. Thirty-seven patients had adequate lung function and 35 were deemed unsuitable for pneumonectomy on the basis of inadequate pulmonary reserve (n = 31) or cardiac risk factors (n = 4). Squamous cell carcinomas (68%) and adenocarcinomas (26%) predominated. Upper lobectomy was performed in 48 patients, lower and middle lobectomy in 13, and right upper and middle bilobectomy in 11. Hospital mortality was 4% (3/72) and compares with a hospital mortality of 9% in 56 consecutive pneumonectomies between 1986 and 1990. Major complications occurred in 11% (bronchopleural fistula 1, persistent atelectasis 4, pneumonia 4). Adjusted actuarial survival after sleeve lobectomy at 1 and 5 years was 84% and 42%, compared with 76% and 44% after pneumonectomy. Five-year survival after lower and middle lobectomy in 13 patients (52%) was similar to that after upper lobectomy (46%), suggesting that in carefully selected patients the concept of sleeve lobectomy can be applied to all pulmonary lobes. N1 disease and compromised lung function were associated with lower survival (N1 38% vs N0 57%; compromised 20% vs adequate 55%). Comparison of preoperative and postoperative lung function and quantitative ventilation-perfusion isotope studies substantiated the preservation of pulmonary function in this group of patients. Sleeve lobectomy is the procedure of choice for anatomically suitable carcinomas or when reduced pulmonary reserve precludes extensive resection.

Assessment of preoperative accelerated radiotherapy and chemotherapy in stage IIIA (N2) non-small-cell lung cancer.

Forty patients with N2 non-small-cell lung cancer (stage IIIA), as determined by mediastinoscopy, were entered into a preoperative neoadjuvant study of chemotherapy (platinum, 5-fluorouracil, vinblastine) and accelerated radiotherapy (150 cGy twice per day for 7 days) for two cycles. Surgical resection was then performed and followed up with an additional cycle of chemotherapy and radiotherapy. All patients completed preoperative therapy. A major clinical response was seen in 87% of patients. Thirty-five patients underwent resection (one preoperative death, one refused operation, one had deterioration of pulmonary function, and two had pleural metastases). Operative mortality rate was 5.7% (2/35). Sixty percent of patients had no complications. Major complications included pulmonary emboli (three), pneumonia (two), and myocardial infarction (one). Down-staging was seen in 46% of patients, with two patients (5.7%) having no evidence of tumor in the specimen, five patients having sterilization of all lymph nodes, and nine patients having sterilization of mediastinal nodes but positive N1 nodes. Median survival of 40 patients was 28 months, with a projected 5-year survival of 43%. Patients with downstaged disease had statistically significant improved survival compared with patients whose disease was not downstaged.

Treatment strategies for bronchopleural fistula.

Successful management of chronic postoperative bronchopleural fistula remains a challenge for thoracic surgeons. Forty-two patients (33 referred from other institutions) were treated for major postoperative bronchopleural fistula since 1978. Factors associated with bronchopleural fistula included right pneumonectomy (n = 23), left pneumonectomy (n = 8), long bronchial stump (n = 16), pneumonia (n = 13), radiation therapy (n = 12), stapled bronchial closure (n = 8), prolonged mechanical ventilation (n = 7), recurrent carcinoma (n = 6), and tuberculosis (n = 2). Patients had undergone an average of 3.3 surgical procedures to correct their bronchopleural fistulas during a mean interval of 24 months before our treatment. Bronchopleural fistulas were located in the right main bronchial stump (n = 23), left main bronchial stump (n = 8), right lobar bronchial stumps (n = 10), and tracheobronchial anastomosis (n = 1). Thirty-five patients were treated by suture closure of the bronchial stump, buttressed with vascularized pedicle flaps of omentum (n = 19), muscle (n = 13), or pleura (n = 2). In seven cases, direct suture closure was not possible, and omental (n = 6) or muscle (n = 1) flaps were sutured over the bronchopleural fistula. Suture closure without pedicle coverage was performed successfully in one case. Initial repair of the fistula was successful in 23 of 25 patients treated with omentum, in nine of 14 patients treated with muscle and in neither of two patients treated with pleural flaps. In nine patients with persistent or recurrent bronchopleural fistula after our initial repair, four underwent a second procedure (three successful) and five were managed with drainage only. The fistula was successfully closed in 11 of 12 patients who had received high-dose radiation therapy (nine with omentum). Overall, successful closure of bronchopleural fistula was achieved in 36 of 42 patients (86%). Four in-hospital deaths resulted from pneumonia and sepsis, two in patients with recurrent bronchopleural fistula after pleural flap closure. In 16 patients the empyema cavity was obliterated during definitive repair of the fistula. The cavity resolved with drainage in four others, nine had draining cavities at follow-up, and one was lost to follow-up. Ten patients required a total of 17 Clagett procedures and one had a delayed myoplasty. Direct surgical repair of chronic bronchopleural fistula may be achieved in most patients after adequate pleural drainage by suture closure and aggressive transposition of vascularized pedicle flaps. Omentum is particularly effective in buttressing the closure of bronchopleural fistulas.