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.

Trial of a novel synthetic sealant in preventing air leaks after lung resection.

BACKGROUND: Postoperative air leaks are a major cause of morbidity after lung resections. This study was designed to evaluate the efficacy and safety of a new synthetic, bioresorbable surgical sealant in preventing air leaks after pulmonary resection. METHODS: In a multicenter trial, 172 patients undergoing thoracotomy were randomized intraoperatively in a 2:1 ratio to receive surgical sealant applied to sites at risk for air leak after standard methods of lung closure (treatment group) or to have standard lung closure only (control group). The primary outcome variable was the percentage of patients free of air leakage throughout hospitalization. Secondary outcome variables were the control of air leaks intraoperatively and the time to postoperative air leak cessation. Time to chest tube removal, time to hospital discharge, and safety outcomes were also evaluated. RESULTS: Air leaks were identified before randomization in 89 of 117 patients in the treatment group and in 39 of 55 patients in the control group. Application of the sealant resulted in control of air leaks in 92% of treated patients (p < or = 0.001). A significantly higher percentage of treated patients than control patients remained free of air leaks during hospitalization (39% versus 11%, p < or =0.001). The mean times to last observable air leak were 30.9 hours in the treatment group and 52.3 hours in the control group (p = 0.006). In the treatment group, trends were observed for reduced time to chest tube removal and earlier discharge. No significant difference was identified in postoperative morbidity and mortality between the two groups. CONCLUSIONS: Air leaks after lung resection occur in most patients. The application of this novel surgical sealant appears to be effective and safe in preventing postoperative air leaks.

Mediastinal tumors: diagnosis and treatment.

Mediastinal tumors are uncommon and often asymptomatic if benign. Tumors have a predilection for arising in one of three mediastinal compartments; anterior, middle, or posterior. If symptoms are present, they are usually compressive in origin. Computed tomography is almost always the imaging modality of choice. Benign-appearing lesions are usually resected for cure. Malignant-appearing lesions usually require biopsy by the least invasive route appropriate for the suspected tumor type.

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.

Superior sulcus tumors.

Superior sulcus tumors (also known as Pancoast's tumors) are an unusual presentation of non-small cell lung cancer (NSCLC) that are often initially misdiagnosed. Accurate and thorough staging is necessary prior to treatment and typically includes magnetic resonance imaging if a surgical approach is being considered. Standard therapy has been induction radiation therapy followed by resection, which results in a 5-year survival of about 30%. Complete resection remains the key to long-term survival in localized NSCLC but is difficult to achieve with superior sulcus tumors due to early invasion of bone and to vascular and nervous structures at the apex of the chest. Complete resection has been enhanced by using an anterior trans-cervicomediastinal approach that facilitates resection of anterior-based tumors that invade the subclavian vessels. Recently, induction chemoradiotherapy has been reported to enhance complete resection rates and improve survival compared with historical controls and is likely to become the new standard treatment for localized superior sulcus tumors.

Repair of esophageal perforation after treatment for achalasia.

Esophageal perforation after treatment for achalasia is a devastating complication. Successful closure of the perforation and relief of the obstruction from achalasia are paramount. This can be accomplished by careful closure of the mucosa. The mucosal closure is buttressed by a pedicled intercostal muscle carefully sewn to the edges of the muscular defect. This approach deals effectively with the perforation and maintains the myotomy for relief of esophageal obstruction from achalasia.

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.

Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival.

BACKGROUND: The principal feature of bronchoalveolar carcinoma is that it spreads along airways or aerogenously with multifocality, but many issues are unresolved. METHODS: We studied 119 patients with pathologically confirmed bronchoalveolar carcinoma. Symptoms, smoking status, radiologic findings, the size of tumor, operative procedures, and complications were reviewed. We studied the pathologic features: presence or absence of aerogenous spread, patterns of growth, cell type, nuclear grade, mitosis, rate of bronchoalveolar carcinoma in adenocarcinoma, and lymphocyte infiltration. The correlation among clinical, radiologic, and pathologic findings was examined, and the factors affecting survival were analyzed. RESULTS: Symptomatic patients had more infiltrative radiographic features, and asymptomatic patients tended to have more mass-like features (P <.0001). Tumors with radiographically infiltrating lesions tended to have mucinous histologic features (P =.006). Tumors with mass lesions by radiograph tended to have nonmucinous and sclerosing histologic features (P =.003). Aerogenous spread was seen in 94% of specimens. The presence of a variety of cell types suggested multiple clonal origin. The overall survival in those patients undergoing resection was 69.1% at 5 years and 56.5% at 10 years. The significant factors affecting survival were radiologic presence of a mass or infiltrate, pathologic findings of the presence of sclerosis, association with a scar, the rate of bronchoalveolar carcinoma in adenocarcinoma, lymphocyte infiltration grade, nodal involvement, and status of complete resection. Mitosis or nuclear grade of tumor cells did not correlate with survival. CONCLUSIONS: Bronchoalveolar carcinoma showed good overall survival with appropriate surgical procedures. Certain radiologic or pathologic findings correlated with survival. These findings may enhance the ability to predict long-term survival.

Surgical treatment of primary pulmonary sarcomas.

OBJECTIVE: We sought to identify the long-term prognosis after surgical treatment for primary pulmonary sarcoma. METHODS: Twenty-three patients were retrospectively identified as having been treated surgically for primary pulmonary sarcoma between 1981 and 1996. The records of all patients were reviewed, and the histopathology reexamined by a pathologist. RESULTS: Fifteen patients were male and eight female; their ages ranged from 20 to 78 (mean 51) years. Tumors measured between 0.9 and 12.0 (mean 5.2) cm across the greatest diameter. The histologic diagnoses were malignant fibrous histiocytoma (8, three grade 1 or 2, two grade 3), synovial sarcoma (4), malignant schwannoma (3), leiomyosarcoma (3), and one case each of angiosarcoma, intimal sarcoma, epitheloid hemangioendothelioma, fibrosarcoma and primitive neuroectodermal tumor. Three patients were found to be unresectable. All three underwent radiation and chemotherapy. Lobectomies or bilobectomies were performed in 13 patients including two sleeve resections, one carinal resection, and one chest wall resection. Four patients underwent radical pneumonectomies. Three patients with invasion of the pulmonary artery, pulmonary veins or atrial wall underwent extended resections with the use of cardiopulmonary bypass. In two, a homograft was used to reconstruct the right ventricular outflow tract. Of the resected patients, six had a positive resection margin, and four had at least one positive lymph node in the specimen. Three patients underwent repeat pulmonary resections for recurrences. Eleven patients received postoperative chemotherapy and eight had radiation therapy. Follow-up was available on 22 patients, and ranged from 2 to 183 (mean 48) months; 14 patients are disease free, six died of disease, one died of surgical complications (operative mortality 5%), and two are alive with disease. Actuarial 3- and 5-year survival of the resected patients was 69%. Size and grade were not found to be correlated with significantly increased survival, but completeness of resection was (P<0.05). CONCLUSIONS: Resection of primary pulmonary sarcomas can produce an acceptable survival rate if the resection is complete. Cardiopulmonary bypass can be a useful adjunct when tumors involve a resectable area of the heart or great vessels.

Superior sulcus lung tumors: impact of local control on survival.

OBJECTIVES: Our goal was to assess patient survival and response to treatment for superior sulcus tumors treated with combined radiation therapy and surgery when possible, or with radiation alone when surgery was not possible. METHODS: Seventy-three patients were treated for primary non-small cell carcinoma of the superior pulmonary sulcus. Thirty-four patients received combined resection and irradiation. Thirty-nine patients who had extensive primary disease, distant metastases, or who were medically unfit for surgery were treated with radiation alone. Thirty-one patients (91%) assigned to the resection/irradiation group completed treatment. Combined therapy patients routinely received 40 Gy before the operation, with additional postoperative irradiation based on the surgical findings. RESULTS: Overall survival at 5 years was 19% and disease-specific survival was 20% for all patients. Overall survival and disease-specific survival at 5 years for the resection/irradiation group were 33% and 38%, respectively. Significant indicators of poor prognosis included unresected primary disease, low performance score, T4 stage, or positive node status. Eighty-two percent of the patients who received irradiation alone were treated with palliative intent. Freedom from local-regional progression, achieved initially in 66% of these patients, was associated with a median survival of 8 months. Median survival for 7 patients considered for definitive irradiation was 25 months. During the first 18 months, distant failures occurred in approximately 35% of patients in each treatment group. CONCLUSIONS: Selection of medically fit patients with resectable disease for combined surgery and aggressive radiation therapy resulted in a high likelihood of local control. Overall survival for the resection/irradiation group was significantly poorer for patients with T4 stage, nodal disease, or Horner's syndrome. Distant metastases eventually developed in 56% of patients undergoing resection. Median survival in the resection/irradiation group was significantly prolonged for those patients who could tolerate high-dose radiation treatment.

Primary tracheal tumor management.

Adenoidcystic carcinoma and squamous carcinoma are the most common tracheal tumors. Resection and postoperative radiation therapy are the treatment of choice. Complete resection is the desired goal and demands knowledge of the principles of tracheal surgery. Benign tumors are best treated by resection and cure can be expected.

Long-segment colon interposition for acquired esophageal disease.

BACKGROUND: Long-segment colon interposition has been used for esophageal replacement for acquired esophageal disease. The indications for use, morbidity, and functional results of these conduits have been debated. METHODS: We reviewed the medical records, office visits, and operative reports of patients undergoing long colon interposition for acquired esophageal disease at our institution from 1956 to 1997. RESULTS: Long colon interposition was performed in 52 patients for caustic injury (n = 20), gastroesophageal disease (n = 16), previous irradiation (n = 8), primary motility disorders (n = 4), and acquired absence of the esophagus (n = 4). From 1976 to 1997, acquired diseases accounted for 62% of long colon interposition. The left colon was used in 46 patients and the right colon in 6. The in-hospital mortality rate was 4%. Early complications included graft ischemia in 5 patients, anastomotic leak in 3, and small bowel obstruction in 1. Late complications included anastomotic stenosis requiring dilation in 26 patients, with 2 requiring surgical revision, and bile reflux requiring surgical diversion in 1 patient. Swallowing function was excellent in 24% of patients, good in 66%, and poor in 10%. CONCLUSIONS: Long colon interposition can be performed safely, with acceptable long-term functional results in patients with acquired esophageal disease.

Induction immunosuppression for lung transplantation with OKT3.

BACKGROUND: The use of OKT3, an anti-CD3 monoclonal antibody, for immunosuppressive therapy for lung transplantation has been restricted because of concerns regarding infectious risk and cardiopulmonary instability after its administration. METHODS: Fifty-two patients received OKT3 (5 mg/d intravenously for 10 days) for induction of immunosuppressive therapy, along with azathioprine (1.5 mg x kg(-1) x d(-1) intravenously) and enteral cyclosporine (12 mg x kg(-1) x d(-1)). Maintenance steroid therapy was begun on postoperative day 8. Prophylactic antifungal therapy (fluconazole or amphotericin B) and ganciclovir was used in all patients. Serial transbronchial biopsy and measurements of pulmonary function were used to assess patients for evidence of infection or rejection. Cytomegalovirus infection was diagnosed by biopsy or the presence of cytomegalovirus antigenemia. RESULTS: The 30-day mortality rate was 4%; the in-hospital mortality rate was 8%. Acute graft failure was seen in 6 patients. The median length of intubation was 5 days, and the median hospital stay was 30 days. Systemic and pulmonary artery systolic pressures, cardiac index, and ratio of arterial partial oxygen pressure to fraction of inspired oxygen showed no significant alteration after OKT3 dosage. Gram-negative pulmonary infections were identified in 12 patients. Aspergillus infection was seen in 7 patients. Cytomegalovirus infection in 8 patients responded to ganciclovir and did not affect mortality. Respiratory syncytial viral infection was seen in 7 patients. Acute rejection was never seen during OKT3 administration. No episodes of acute rejection were identified in 14 patients at any time postoperatively. In the remainder, episodes of acute rejection responded to steroid or antithymocyte globulin therapy. At a median length of follow-up of 31 months, freedom from obliterative bronchiolitis was 69%+/-9% at 36 months. The overall survival rate was 88%+/-5% at 12 months, 82%+/-6% at 24 months, and 74%+/-7% at 36 months after transplantation. CONCLUSIONS: OKT3 is a safe and effective agent for induction immunosuppressive therapy in lung transplant recipients that limits the incidence of acute rejection and may decrease the incidence of obliterative bronchiolitis.

Clinical experience with carinal resection.

OBJECTIVE: Pathologic processes that involve the carina pose a tremendous challenge to thoracic surgeons. Although techniques have been developed to allow primary resection and reconstruction, few institutions have accumulated sufficient experience to allow meaningful conclusions about the indications and the morbidity and mortality rates for this type of surgery. METHODS: Since 1962, 135 patients have undergone 143 carinal resections (134 primary resection, 9 re-resection) at our institution. Indications for carinal resection included bronchogenic cancer (58 patients), other airway neoplasms (60 patients), and benign or inflammatory strictures (16 patients). Thirty-seven patients (28%) had a history of prior lung or airway surgery not involving the carina. Carinal resection without pulmonary resection was accomplished in 52 patients; 57 patients had carinal pneumonectomy (44 right, 13 left); 14 patients had carinal plus lobar resection, and 11 patients had carinal resection after pneumonectomy (9 left, 2 right). There were 15 different modes of reconstruction, based on the type and extent of resection. Techniques were used to reduce anastomotic tension. RESULTS: The operative mortality rate in the 134 patients after primary carinal resection was 12.7%. Adult respiratory distress syndrome was responsible for 9 early deaths. Predominant predictors of operative death included postoperative mechanical ventilation (P =.001), length of resected airway (P =.03), and development of anastomotic complications (P =.04). Mortality rates varied by the type of procedure and the indication for resection. Left carinal pneumonectomy was associated with a high operative mortality rate (31%). Complications were noted in 52 patients (39%), including atrial arrhythmias (20 patients) and pneumonia (11 patients). Anastomotic complications, both early and late, were seen in a total of 23 patients (17%) and resulted in death or surgical reintervention in 21 patients (91%). The operative mortality rate for carinal re-resection was 11.1%. CONCLUSIONS: Carinal resection with primary reconstruction may be accomplished with acceptable mortality rates, but the underlying pathologic process and chance for long-term survival must be carefully considered before the operation is recommended, especially in the case of left carinal pneumonectomy. Anastomotic complications exact a heavy toll on involved patients. Careful patient selection and meticulous anesthetic and surgical technique remain the key to minimizing morbidity and mortality rates.

Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection.

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.

Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study.

OBJECTIVE: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma. We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates. METHODS: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m2) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor). The mean age was 62 years, and 32 patients (80%) had adenocarcinoma. Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater). RESULTS: The average hospitalization for induction treatment was 17 days. Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication. The maximum tolerated dose of paclitaxel was 100 mg/m2. Two patients died during induction treatment. Thirty-six patients (90%) underwent resection. The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response. Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076). The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months. CONCLUSIONS: Paclitaxel at a dose of 100 mg/m2 appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival.

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.