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The purpose of this study is to compare the morbidity and mortality of right versus left pneumonectomy.We used a retrospective review of pneumonectomies performed during the period 1990 to 2000 and included a meta-analysis of relevant literature.There were 187 pneumonectomies: 68 right, 119 left. The primary study end point was in-hospital death. There were 11 deaths: 7 (10.3%) right, 4 (3.3%) left (p = 0.10). Six deaths were attributable to bronchopleural fistula and its subsequent complications. The risk of bronchopleural fistula was higher on the right (9 [13.2%]) versus left (6 [5.0%]; p = 0.0472), as was the mortality associated with bronchopleural fistula (4 of 9 [44%] right versus 2 of 6 [33%] left). Right pneumonectomies were more likely to require an intrapericardial or extended dissection (p = 0.003), hand-sewn bronchial closure (p0.0001), or the closure buttressed (p0.0001). By univariate analysis, factors associated with an increased mortality were bronchopleural fistula (p0.0001), hand-sewn closure (p = 0.001), and a history of smoking (p = 0.01). By multivariate analysis, the most important factor was bronchopleural fistula (odds ratio, 43.3; 95% confidence limits, 4.2 to 441.9; p = 0.002). A meta-analysis combining our results with those from the literature found increased mortality of right pneumonectomy with a relative risk of 3.39 (95% confidence limits, 2.10 to 5.48; p0.00001).Right pneumonectomy is associated with a higher mortality even in the absence of induction therapy. This is primarily related to the increased risk of bronchopleural fistula on the right. The increased number of bronchopleural fistulas on the right may be attributable to more extensive resection. Addressing technical factors that contribute to early bronchopleural fistula may reduce the mortality of right pneumonectomy.

Summary Purpose: This is a phase II study to assess the role of induction chemotherapy in the management of stage IIIA non-small-cell lung cancer (NSCLC). We are now reporting the long-term follow-up of the Toronto phase II trial. Methods: Sixty five patients with mediastinoscopy proven stage IIIA NSCLC received two cycles of preoperative MVP or VLB/P followed by thoracotomy followed by two further courses of chemotherapy. Results: The overall response rate was 67.7% with three complete and 41 partial responders. Forty seven patients went on to thoracotomy with 35 complete resections. Pathologically 4.6% of patients had no tumour remaining. There were three postop deaths as well as five chemotherapy related deaths. Of the 35 patients completely resected 19 have recurred including eight in brain. The median survival for the entire 65 patients is 18.6 months with a 1 year survival of 66%, 5 year survival of 29% and a 10 year survival of 22%. Conclusions: The long-term survival of induction chemotherapy is maintained. The high incidence of brain recurrences warrants assessment of the role of prophylactic cranial radiation. The role of surgery for stage IIIA NSCLC following induction chemotherapy awaits further study.

Objectives: To examine our results with surgery for locally advanced non-small cell lung cancer (NSCLC) invading the superior vena cava (SVC). Methods: A retrospective analysis of patients who underwent resection between 1988 and 2003 was performed. Postoperative morbidity, long-term survival, including risk factors for overall and disease-free survival were examined. Results: Median age of the 15 operated patients was 60 years (28–78). All had direct SVC invasion by tumor. All underwent mediastinoscopy. Seven patients with N2 disease, and one with a bulky right upper lobe tumor received induction therapy. Eight underwent lobectomy (three sleeve), and seven had pneumonectomy (two carinal). The SVC was replaced by interposition graft in nine patients, whereas six had partial resection. There were two postoperative deaths (14%) and three major morbidities (23%). There was one late graft thrombosis. Mean follow-up was 25 months (3–132, median 11). Overall 1 and 3-year survival was 68 and 57% and disease-free survival was 55 and 27%, respectively. All late deaths were due to recurrence. Survival of patients with N2 disease was not significantly worse than those with localized (N0/N1) nodal disease. There was a trend towards later recurrence in patients who had induction therapy (median disease-free interval of 29 months versus 5 months in the untreated group, P =0.3), but there was no significant effect on overall survival. The extent of lung resection and type of SVC procedure did not influence long-term survival. Conclusions: Carefully selected patients with NSCLC and SVC involvement can be operated upon with acceptable postoperative morbidity and mortality. Induction therapy appears to delay recurrence.

Chemoradiotherapy remains a gold standard in the treatment of limited-disease small cell lung cancer. Currently, three indications for the surgical treatment of very limited disease (stage I, II, or highly selected IIIa) small cell lung cancer can be identified: (1) primary surgery in peripheral clinical N0 lesions followed by adjuvant chemotherapy or chemoradiotherapy; (2) primary chemotherapy or chemoradiotherapy followed by surgery +/− radiotherapy in patients with a good response to initial treatment; and (3) salvage operations in patients who recur or persist at the primary site but still have resectable disease. The value of these approaches has been assessed in retrospective analyses and prospective nonrandomized trials. A large prospective randomized trial failed to prove any added value for surgery in the multidisciplinary treatment of limited-disease small cell lung cancer, but very few very-limited-disease patients were included. Semin Oncol 30:47-56. Copyright 2003, Elsevier Science (USA). All rights reserved.

In non-small cell lung cancer, surgical excision remains the treatment of choice for those tumors limited to the thoracic cavity when a complete (R0) resection can be anticipated. Since its successful introduction over 70 years ago, improvements in clinical staging, preoperative assessment, anesthesia, surgical techniques and perioperative care have allowed the surgeon to offer this approach with the expectation that patients will fare well postoperatively and will potentially be cured of their cancer. Despite these improvements, there is still significant morbidity and mortality associated with pulmonary resections and, unfortunately, a minority of surgically resected patients will remain alive, disease-free five years later. Indeed, in most series, only 40–45% of patients undergoing surgical resection for the management of primary lung cancer will survive five years. It is the purpose of this paper to discuss the expected results following surgical resection, including: the morbidity and mortality of such procedures, the expected five year survival rates and various quality control issues that are now readily identifiable in lung cancer surgery. 2. Morbidity

PURPOSE: Assessment of long-term results of combined-modality therapy for resectable non–small-cell lung cancer is hampered by insufficient follow-up and small patient numbers. To evaluate this, we reviewed our collective experience. PATIENTS AND METHODS: This study was a retrospective chart review recording demographics, tumor stage, treatment, and outcome of consecutive patients undergoing surgery. Survival was analyzed by Kaplan-Meier, and prognostic factors were analyzed by log-rank and Cox regression. RESULTS: From January 1993 to December 1999, 470 patients were treated, with follow-up in 446: 27 stage I, 55 stage II, 316 stage III, 43 stage IV (solitary M1), and five uncertain. Chemotherapy was mitomycin/vinblastine/cisplatin (174 patients [39.0%]), carboplatin/paclitaxel (148 [33.2%]), and other combination (124 [27.8%]); 75 patients (16.8%) received induction radiation. Resection was complete in 77.4%, incomplete in 8.3%, attempted but with gross residual disease afterward in 1.8%, and not performed in 12.6%. Pathologic complete response occurred in 20 patients (4.5%). With median follow-up of 31.0 months for patients still alive, median and 3-year survival for pathologic stages 0, I, II, III, and IV were more than 90 months, 73%; 42 months, 52%; 23 months, 35%; 16 months, 28%; and 16 months, 23% (P < .001). In a multivariate analysis, age, complete resection, pathologic stage, and pneumonectomy, but not induction regimen, significantly influenced survival. CONCLUSION: Although pathologic complete response outside the protocol setting is low, survival of this large patient cohort is comparable to that of patients in published combined-modality trials. Survival is significantly influenced by patient age, complete resection, pathologic stage, and pneumonectomy. These results can help guide standard clinical practice and emphasize the need for novel induction regimens.

Background . The 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) imaging is an advance over computed tomography alone in the staging of untreated nonsmall cell lung cancer (NSCLC). Aside from one 9-patient study, there are no data comparing FDG-PET imaging with surgical staging of NSCLC after induction therapy. Methods . We reviewed our institutional experience with FDG-PET imaging followed by surgical staging of nonsmall cell lung cancer after induction therapy. A nuclear physician blinded to surgical findings reviewed the FDG-PET scans and assigned a clinical TNM stage. A thoracic surgeon assigned a pathologic TNM stage. Then the clinical TNM stage and the pathologic TNM stage were compared. Results . Fifty-six patients (30 males and 26 females; median, age 60) with nonsmall cell lung cancer underwent chemotherapy (40 patients), chemoradiation (11 patients), or radiation alone (5 patients) followed by PET and operations. PET had a positive predictive value of 98% for detecting residual viable disease in the primary tumor. PET over-staged nodal status in 33% of patients, under staged nodal status in 15%, and was correct in 52%. PET correctly classified all patients with M1 disease. Conclusions . Positron emission tomography after induction therapy accurately detects residual viable primary tumor, but not the involvement of mediastinal lymph nodes.

Malignant pleural mesothelioma (MPM) is an uncommon tumor with approximately 2000 to 3000 new cases diagnosed in United States each year. The incidence varies from 13 to 33 to 66 per million per year in the United States, South Africa, and Western Australia, respectively. Between 1940 and 1970, there has been a steady increase in the incidence due to occupational exposure to asbestos, and is expected to peak somewhere between 1990 and 2010. However, additional factors are likely to contribute to the development of this malignancy, since approximately 20% of patients who develop MPM have no history of asbestos exposure. Regardless of its cause, the natural history of MPM is one of locoregional progression of disease with the ultimate development of distant metastases. Despite aggressive multimodality therapy, the median survival of patients diagnosed with this disease ranges from 9 months to 20 months. The association of asbestos with MPM was first recognized by Wagner et al. and confirmed by others. Asbestos fibers lodged in the respiratory bronchioles and alveoli promote alveolar inflammation, interstitial pneumonitis, and eventual fibrosis, resulting in the clinical syndrome of asbestosis. The fibers are also conveyed to the pleural space by subpleural lymphatics where chronic inflammation and subsequent fibrosis form parietal pleural plaques. Such plaques can transform into malignant mesothelioma. Initially manifesting as small nodules, they coalesce and ultimately invade adjacent structures such as the visceral pleura, mediastinum, pericardium, and diaphragm. The tumor is notorious for its nonspecific presentation and extensive local infiltration. Diagnosis is often delayed by 2 months and even beyond 6 months in a quarter of patients. Overall median survival of unresected patients ranges from 7 to 11 months, with more than 80% of patients succumbing to local disease rather than metastatic spread. While the natural history of this debilitating disease is well recognized, treatment options are limited and controversial. In addition, there is no “standard” therapy in the management of patients with this disease. Surgery, radiation therapy, chemotherapy, and immunotherapy have all been used with varying success. More recently, multimodality treatment regimens have combined surgery with adjuvant radiation therapy and chemotherapy. However, most patients with this disease have been treated in an individualized manner, and this has hampered the ability to accurately identify factors of prognostic significance. Despite the limitations just described, earlier retrospective and recent prospective studies have identified prognostic variables using univariate and multivariate analyses of large groups of patients with MPM. These factors can be broadly grouped into clinical and pathologic factors. Clinical factors associated with a favorable prognosis include: (1) age less than 65, (2) absence of chest pain, (3) long duration of symptoms, (4) weight loss of less than 5% at presentation, (5) good performance status, and (6) a normal platelet count. Surgical–pathologic factors include (1) epithelial histology, (2) absence of nodal metastases, (3) early surgical–pathologic stage, and (4) complete resection. Although some of the clinical factors identified by univariate analysis lose their statistical significance when evaluated by multivariate analysis, they remain important because they often serve to identify patients with advanced disease who are unlikely to benefit from aggressive multimodality therapy. Keywords: stage; histologic type; age; weight loss; ECOG performance status; completeness of resection; symptoms; gender

Background . The risks of complications in patients undergoing thoracotomy after neoadjuvant therapy for nonsmall cell lung cancer remain controversial. We reviewed our experience to define it further. Methods . All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events. Results . Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy ( p = 0.02), blood loss ( p = 0.01), and forced expiratory volume in one second (percent predicted) ( p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate. Conclusions . Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.

Video-assisted thoracic surgery (VATS) has become an accepted approach for the diagnosis and treatment of thoracic malignancies. Port site tumor recurrence is a reported complication of VATS. However, the true incidence of this problem is unknown. To try to determine the incidence of port site recurrence, we analyzed our experience with patients undergoing VATS wedge resection for malignancy.Data were obtained from our prospective VATS database. The analysis was confined to patients undergoing VATS wedge resection for malignancy, excluding those having a pleural biopsy only. Parameters analyzed included demographic factors, surgical technique, and port site recurrences identified by physical examination, CT scan, or both.From 1992 to 1996, 410 patients (182 men, 228 women; median age = 61 years) underwent a VATS wedge resection for malignancy. The procedure was performed for diagnosis or staging in 90% of cases. Access incisions plus port sites were used in 97 (24%) patients; port sites only were used in 313 (76%) patients. Conversion to thoracotomy was necessary in 102 patients (25%) either for definitive resection (58 patients) or because VATS was not technically adequate (44 patients). Specimens were retrieved via access incisions or port sites with or without a specimen bag. The operative mortality was 0.25%. With long-term follow-up (median = 25 months) available for 374 patients (91%), only one port site recurrence was identified (0.26%).Our experience confirms the safety of VATS wedge resection in cancer patients. The incidence of port site tumor recurrence is low when oncologic principles are respected. In our institution, these principles include performing VATS wedge resection only for lesions that can be widely removed; converting to thoracotomy for definitive or extensive cancer operation; and using meticulous technique for the extraction of specimens from the pleural space.

The authors review the management of postpneumonectomy bronchopleural fistulae and describe the place of the transsternal transpericardial approach, especially in the management of recalcitrant postpneumonectomy bronchopleural fistulae. The technique is described in detail, and the results of the published series are analyzed. The authors do recommend the use of this approach in the recalcitrant fistula that has failed standard approaches.

Background: The treatment of superior sulcus lung cancers is evolving and preoperative chemotherapy is increasingly used. To establish a historical benchmark against which new therapies can be assessed, we reviewed our 24-year experience with patients undergoing thoracotomy for lung cancers of the superior sulcus. Methods: Data were acquired through retrospective chart review. Overall survival was calculated by the method of Kaplan and Meier, and prognostic factors were examined by log rank and Cox proportional hazards modeling. Results: From 1974 to 1998, 225 patients underwent thoracotomy. The patients included 144 men (64%) and 81 women with a median age of 55 years. The majority of patients (55%) received preoperative radiation, but 35% did not have any preoperative treatment. Tumor stages were IIB (T3 N0) in 52%, IIIA in 15%, and IIIB in 27% of patients. Complete resection was achieved in 64% of T3 N0 tumors, 54% of T3 N2 tumors, and 39% of T4 N0 tumors. Operative mortality was 4%. Median survival was 33 months for stage IIB and 12 months for both stages IIIA and IIIB. Actuarial 5-year survivals were 46% for stage IIB, 0% for stage IIIA, and 13% for stage IIIB. By univariate and multivariable analyses, T and N status and complete resection had a significant impact on survival. Locoregional disease was the most common form of relapse. Conclusions: Our results provide a benchmark against which new treatment regimens can be evaluated. Control of locoregional disease remains the major challenge in treating lung cancers of the superior sulcus. The potential benefit of preoperative chemotherapy or chemoradiotherapy must be assessed by whether it leads to higher rates of complete resection and a lower risk of local relapse. (J Thorac Cardiovasc Surg 2000;119:1147-53)

Background . In patients with unresectable pulmonary metastases from sarcoma, systemic chemotherapy has had limited efficacy possibly because of dose-limiting toxicities. Isolated lung perfusion is an alternative method of delivering high-dose chemotherapy to the lungs while minimizing systemic toxicities. We present the results of our Phase I trial of isolated lung perfusion with doxorubicin hydrochloride in such a group of patients. Methods . From May 1995 to June 1997, 8 patients with unresectable metastases from sarcoma limited to the lungs underwent isolated lung perfusion with doxorubicin. A dose-escalation schedule starting at 40 mg/m 2 was used. Seven patients were treated with a dose of 40 mg/m 2 or less, and 1 patient received 80 mg/m 2 . Blood, tumor, and normal lung samples were obtained at various time points during the operation. Patients were evaluated for cardiac, pulmonary, and other toxicities. Results . The doxorubicin concentrations in both normal lung and tumor correlated directly with the amount of doxorubicin in the perfusate. The tumors took up less doxorubicin than the lung. All patients had minimal or undetectable systemic levels of doxorubicin at the conclusion of the perfusion. There were no cardiac or other systemic toxicities. In the 7 patients perfused with 40 mg/m 2 or less of doxorubicin, there was a significant decrease in the forced expiratory volume in 1 second and a trend toward a significant decrease in diffusing capacity. The patient who received 80 mg/m 2 underwent lung scanning postoperatively, and scans showed no ventilation or perfusion in the perfused lung. There were no perioperative deaths. Two patients are alive with disease, and 6 patients died of disease. The median follow-up is 11 months and the longest, 31 months. There were no partial or complete responses. One patient had stabilization of disease in the perfused lung, whereas the lesions in the untreated lung progressed markedly. Conclusion . Isolated lung perfusion is well tolerated by patients and effectively delivers high doses of doxorubicin to the lung and tumor tissues while minimizing systemic toxicities. A single dose of 80 mg/m 2 resulted in substantial injury to the lung. There were no partial or complete responses in patients perfused with doxorubicin at the maximum tolerated dose of 40 mg/m 2 . Isolated lung perfusion remains a model for testing new and innovative therapies for metastatic sarcoma.

Regional lymph nodes (RLNs) possess important immune functions and represent a major pathway of metastasis for solid tumors. Given these facts, the ability to transfer exogenous genes to the RLNs with the goal of manipulating the local immunological milieu would be desirable. On the basis of the hypothesis that a significant proportion of adenovirus (Ad) gene transfer vectors traffic through the lymphatics, E1-E3- Ad vectors were injected into the hind footpad of C3H/He mice and the RLNs assessed for vector trafficking and transgene expression. A low dose (10(9) particles) of an Ad vector encoding the firefly luciferase gene (Ad-CMV.Luc) resulted in luciferase expression only in the injection site and RLNs, with no detectable systemic (liver, spleen, lung) expression. At a higher dose (10(11) particles), some expression could be detected systemically in addition to the RLNs, but at levels in liver 14-fold less than in the RLNs. Transgene expression in the RLNs was transient, peaking at 1 day, decreasing markedly by 7 days. At high doses (10(11) particles), interruption of draining lymphatics decreased the amount of systemic dissemination 22-fold, suggesting that a large proportion of the vector trafficks through the lymphatics before reaching the systemic circulation. Administration of a vector encoding the jellyfish green fluorescent protein gene (AdCMV.GFP, 10(11) particles) showed that transgene expression in the RLNs was primarily in the cortical area. After footpad injection of a fluorescent-labeled Ad vector (Cy3-AdCMV.Null), fluorescent virions were visualized in the draining lymph. Regional lymph collected from animals injected in the footpad with AdCMV.Luc (10(11) particles) contained functional vector. Augmentation of local immune function in the RLNs was achieved by footpad administration of an Ad vector encoding murine IL-12, resulting in high mIL-12 and IFN-gamma levels in the regional, but not distant, nodes. These data demonstrate that expression of exogenous genes in RLNs is easily accomplished with Ad vectors, Ad vector dissemination occurs primarily via the lymphatics after footpad administration in mice, and basic immune functions in the RLNs can be manipulated by Ad-mediated gene transfer in vivo.

Objective: This phase II trial assessed the feasibility, as measured by response rate, toxicity, resectability rate, and surgical morbidity and mortality rates, of perioperative paclitaxel and carboplatin chemotherapy in patients with early-stage non–small cell lung carcinoma. Methods: All patients required negative mediastinoscopy results and adequate medical parameters to undergo induction chemotherapy and an operation. Superior sulcus patients were excluded. Chemotherapy consisted of paclitaxel 225 mg/m 2 over 3 hours and carboplatin (area under the curve=6) every 21 days for 2 cycles preoperatively. Three postoperative cycles of chemotherapy were planned for patients undergoing complete resection. Results: Between June 1996 and July 1998, 94 patients were entered into the study. Sixty-five (69%) were men, and the median age was 64 years (range, 34-79 years). After induction chemotherapy, 53 of 94 (56%; 95% confidence interval, 46%-67%) had a major objective response, 88 (94%) underwent surgical exploration, and 81 (86%; 95% confidence interval, 78%-92%) underwent complete resection. Reasons for not undergoing an operation included disease progression (n = 3), clinically unresectable status (n = 1), death (n = 1), and patient lost to follow-up (n = 1). Two postoperative deaths occurred. Six (6%; 95% confidence interval, 0%-13%) pathologic complete responses were observed. Ninety (96%) patients received the planned preoperative chemotherapy versus 45% receiving postoperative chemotherapy. No unexpected chemotherapy or surgical morbidity occurred. The 1-year survival is currently estimated at 85%, and the median survival has not yet been reached. Conclusions: Induction chemotherapy with paclitaxel and carboplatin is feasible and produces a high response rate with acceptable morbidity and mortality rates in early-stage non–small cell lung carcinoma. A prospective randomized trial comparing 3 cycles of induction chemotherapy and surgery with surgery alone in early-stage non–small cell lung carcinoma is planned. (J Thorac Cardiovasc Surg 2000;119:429-39)

Background . Although sublobar and lobar resections are accepted operations for pulmonary metastases, pneumonectomy is viewed as a major incursion on Stage IV patients. We considered it important to ascertain the current results of pneumonectomy for pulmonary metastases since little information is available. Methods . Of the 5,206 patients with pulmonary metastasectomy reported by the International Registry of Lung Metastases, 133 (3%) underwent primary, and 38 (1%) completion pneumonectomy between 1962 and 1994. Data were analyzed to determine the operative mortality rates, survival rates, and determinants of survival. Results . Primary pneumonectomy was performed for metastatic disease mainly from epithelial (49%, 65 of 133) and sarcomatous (33%, 43 of 133) tumors. Indications were central lesion, eg, proximal endobronchial or hilar nodal metastases. Operative mortality was 4% (4 of 112) and a 5-year survival rate of 20% was achieved following complete resection (R0) in 112 patients. In contrast, the 21 incompletely resected patients had an operative mortality rate of 19% (4 of 21), and the majority did not survive beyond 2 years ( p = 0.02). Survival was determined by the completeness of resection and not histology of the primary tumor, number of metastases, nodal status, and disease-free interval. In the 38 completion pneumonectomy patients, 35 were operated for recurrent disease and 3 for residual disease. Sarcomatous secondaries predominated in 28 patients. Complete resection was achieved in 31 patients (82%). The operative mortality rate was 3% (1 of 38 patients) and the 5-year survival rate was 30%. Conclusions . Pneumonectomies for pulmonary metastases, albeit infrequently performed, were associated with acceptable operative mortality and long-term survival when performed in selected patients amenable to complete resection.

BACKGROUND Cisplatin-based induction chemotherapy before surgery or irradiation has improved the survival of patients with Stage III nonsmall cell lung carcinoma (NSCLC). Encouraged by earlier results with preoperative MVP (cisplatin [120 mg/m2 or 25 mg/m2/week], vinblastine, and mitomycin) for Stage IIIA patients with clinically apparent mediastinal (N2) disease, the authors conducted a Phase II trial of the safety and efficacy of induction MVP400 with the dose intensity of cisplatin doubled from 25 to 50 mg/m2 per week. METHODS From October 1992 to March 1996, 37 patients with Stage IIIA (26) or Stage IIIB (11) NSCLC began the MVP400 induction chemotherapy program. Four doses of cisplatin (100 mg/m2), 7 doses of vinblastine, and 2 doses of mitomycin were given over 9 weeks. Patients received either surgery or irradiation after induction treatment. RESULTS Overall, the response rate was 65% (95% confidence interval, 49–81%) with a complete resection rate of 67%. The median survival was 17 months, with 66% of patients alive at 1 year. Complete resection and Stage IIIA involvement were favorable prognostic indicators for survival. No Stage IIIB patients underwent a complete resection. Myelosuppression was the most common side effect. There were no treatment-related deaths. CONCLUSIONS Although high response and complete resection rates were again demonstrated, results with the MVP400 regimen were not improved over those achieved with MVP regimen tested earlier with Stage IIIA (N2) patients. The authors continue to recommend MVP as an induction chemotherapy regimen for clinical trials. Cancer 1999;86:1189–97. © 1999 American Cancer Society.

Background/Purpose: Mediastinal masses commonly are referred to the pediatric surgeon and can be difficult diagnostic problems. Various techniques have been used to perform biopsy in the mediastinum, but there are few reports of mediastinoscopy or Chamberlain procedure in children in the literature. The authors reviwed their experience with these techniques in a pediatric oncology population. Methods: The medical records of all patients on the pediatric surgical service between 1987 and 1997, inclusive, who underwent mediastinoscopy or Chamberlain procedure were reviewed. Demographic data, diagnostic accuracy, complications, operating time, and blood loss were recorded. Results: Sixteen consecutive patients underwent 13 Chamberlain procedures and six mediastinoscopies over the above period. Diagnostic accuracy was found to be 95% overall (100% for Chamberlain procedure, 83% for mediastinoscopy). Five complications occurred in the Chamberlain group and none in the mediastinoscopy group. No complication required thoracotomy or sternotomy. Among patients whose sole reason for admission was diagnosis of a mediastinal mass, the mean hospital stay was 1.7 +- 0.8 days (n=7) for those who underwent Chamberlain procedure and 1.4±0.9 days (n=4) for those who underwent mediastinoscopy. One mediastinoscopy was performed as an ambulatory procedure. Conclusion: Mediastinoscopy and the Chamberlain procedure are effective and safe techniques for biopsy of mediastinal masses in this age group.

Objective: The purpose of this study was to determine (in survivors of 5 years after resection of their lung cancer) whether age, sex, histologic condition, and age have any influence on furthering survival beyond 5 years. Methods: From 1973 to 1989, 686 patients were alive and well 5 years after complete resection of their lung cancers. Survival analysis was carried out with only deaths from lung cancer treated as deaths. Deaths from other causes were treated as withdrawals. Multivariate Cox regression was used to test the relationship of survival to age, sex, histologic condition, and stage. Results: The population in this study had the following characteristics at the time of operation: The male/female ratio was 1.38:1, and the median age was 61 years. The histologic condition of their lung cancer was adenocarcinoma in 412 patients, squamous cell in 244 patients, large cell carcinoma in 29 patients, and small cell carcinoma in 1 patient. The stage of the disease was stage IA in 263 patients, IB in 261 patients, IIA in 12 patients, IIB in 68 patients, and IIIA in 82 patients. The extent of resection was a lobectomy or bilobectomy in 579 patients, pneumonectomy in 55 patients, and wedge resection or segmentectomy in 52 patients. A recurrence or a new lung primary occurrence was considered as failure to remain free of lung cancer. The median follow-up on all patients was 122 months from initial treatment. Of the 686 patients, 26 patients experienced the development of late recurrence and 36 new cancers, beyond 5 years. Overall survival for 5 additional years after a 5-year check point was 92.4%. Likewise, survival by nodal status was 93% for N0 tumors, 95% for N1 tumors, and 90% for N2 tumors. Survival by stage was 93% for stage I tumors and 91% for stage II or IIIA tumors. Conclusions: In patients with surgically treated lung cancer, neither age, sex, histologic condition, nor stage is a predictor of the risk of late recurrence or new lung cancer. The only prognostic factor appears to be the survival of the patient free of lung cancer for 5 years from the initial treatment, with a resultant favorable outlook to remain well for 10 or more years. (J Thorac Cardiovasc Surg 1999;117:32-8)

Background . This study was designed to determine the prognostic value of positive surgical resection margin or highest nodal station sampled at thoracotomy in patients with non–small cell lung cancer. Methods . Two reviewers independently examined the surgical records and pathologic reports from a randomized trial comparing computed tomography versus mediastinoscopy for staging of lung cancer. They recorded pathologic findings at the surgical resection margin, the highest mediastinal nodal station sampled at thoracotomy, histologic type, tumor size, N status, and evidence of vascular or lymphatic invasion. These variables formed the independent variables in logistic regression models to predict recurrence. Results . Except for 1 patient, follow-up at 3 years for 399 included patients was complete. Significant predictors of recurrence were tumor size (odds ratio [OR], 1.2 (per centimeter); 99% CI [confidence interval], 1.1 to 1.4), and N status (compared with N0, N1: OR, 1.6; CI, 0.8 to 3.1; N2: OR, 3.2; CI, 1.4 to 7.5). Other variables, including positive surgical resection margin, did not predict early recurrence or death. Conclusions . In patients with non–small cell lung cancer, surgical resection margin or highest nodal station sampled at thoracotomy that are involved by carcinoma do not predict recurrence. The current definition of incomplete resection has limited prognostic significance.

Background Pericardial effusions remain a formidable problem in patients with an advanced malignancy. We reviewed our experience with pericardiocentesis and intrapericardial sclerotherapy versus open surgical drainage as the treatment for these effusions. Methods A retrospective review was performed of one surgeon's experience (M.E.B.) with the surgical treatment of malignant pericardial effusions at a tertiary-care cancer center. Results Sixty patients underwent 72 procedures during 8 years. Thirty-seven (51%) pericardiocenteses and 35 (49%) open procedures were performed in patients with effusions. There was no significant difference in the complication rates seen between those effusions drained via pericardiocentesis (n=5; 13%) and those drained in an open surgical procedure (n=5; 14%). Similar results were seen with respect to the development of a recurrent effusion. There were no procedure-related deaths. The median survival for all patients was 97 days. Patients with breast cancer as their primary malignancy survived significantly longer after drainage than did all others ( p =0.01). The type of procedure did not influence survival. Costs of surgical drainage exceed those of pericardiocentesis by nearly fortyfold. Conclusions Pericardiocentesis with intrapericardial sclerotherapy is as effective as open surgical drainage for the management of malignant pericardial effusions.

Locally advanced esophageal cancer, potentially curable with surgery or radiotherapy-based treatment, has a poor prognosis because of the eventual development of systemic metastatic disease in the majority of patients. Local recurrence of disease after local treatment modalities is equally problematic. The use of systemic chemotherapy in the surgical and radiation-based treatment of esophageal cancer is reviewed, including the approach of preoperative chemotherapy, preoperative concurrent chemotherapy plus radiotherapy, and chemoradiotherapy as definitive treatment without surgery. The use of chemoradiotherapy has clearly been shown to be superior to radiotherapy alone in the nonsurgical management of locoregional esophageal cancer. Recent trials suggest that preoperative chemoradiotherapy may be superior to surgery alone but trials are ongoing to better define the role of combined modality therapy in the surgical management of esophageal cancer.

Surgical treatment is offered to all patients with stage I or II disease and to specific groups of patients with stage III or IV disease. Cisplatin based on regimens of induction chemotherapy or chemoradiotherapy have proven to be valuable in stage IIIA (N2) disease. We now recommend induction therapy on an investigational basis to most patients with stage I or II tumors and to all those with stage IIIA tumors, when the 5 year survival is anticipated to be less than 50% with conventional therapy. Many new chemotherapy agents effective in advanced stage lung cancer are currently integrated into this multimodality approach in hopes of further improvement in tumor control and survival.

Purpose : Local failure is a major obstacle to the cure of locally advanced non small-cell lung cancer. Three-dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially representing an enhancement of the therapeutic ratio of radiation therapy for lung cancer. We performed this analysis of 45 non-small cell lung cancer patients treated with 3-DCRT alone, to evaluate the ability of computer derived lung dose volume histograms to predict serious pulmonary toxicity, to assess the feasibility of this approach, and to examine the resulting survival. Methods : There were 28 males (62%) and 17 females (38%). The median age was 65 (range: 38–82). Tumor stage was Stage I/II in 13%, IIIa in 42%, and IIIb in 44%. The histology was squamous in 44%, adenocarcinoma in 36%, and other non-small cell histologies in the others. Only 47% of patients, had combined favorable prognostic factors (i.e. KPS ≤ 80, and ≤5% wt. loss). The median dose of radiation to gross disease was 70.2 Gy (range: 52.2–72 Gy) delivered in fractions of 1.8 Gy, 5 days per week. Results : Seven patients did not complete 3-DCRT due to disease progression outside the port. Follow-up data are mature: the median follow up of the 6 survivors is 43.5 months (35–59). Thoracic progression occurred in 46%. Median survival (all 45 patients.) is 15.7 months and survival is 32% at 2 years and 12% at 59 months. Pulmonary toxicity ≥grade 3 occurred in 9% of patients. Dose volume histograms were available in 31 patients and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% (38) of patients with > 30% of lung volume receiving ≥25 Gy, versus 4% (123) of patients with ≤30% lung receiving ≥25 Gy ( P = 0.04). Grade 3 or higher pulmonary toxicity occurred in 29% (414) of patients with a predicted pulmonary normal tissue complication probability of 12% or higher versus 0% (0/17) in patients with a predicted probability of less than 12% ( P = 0.03). Conclusions : Despite adverse prognostic criteria median survival is encouraging and may be higher than some combined modality approaches. Dose volume histogram parameters may be useful to determine the maximum dose for individual patients and thereby permit avoidance of toxicity.

Background. This prospective study was designed to determine whether diltiazem is superior to digoxin for the prophylaxis of supraventricular dysrhythmias (SVD) after pneumonectomy or extrapleural pneumonectomy (EPP) and to assess the influence of these drugs on perioperative cardiac function. Methods. Seventy consecutive patients without previous SVD were randomly allocated immediately after pneumonectomy or EPP to receive diltiazem (n = 35) or digoxin (n = 35). Diltiazem-treated patients received a slow intravenous loading dose of 20 mg, followed by 10 mg intravenously every 4 hours for 24 to 36 hours, then 180 to 240 mg orally daily for 1 month. Digoxin-treated patients received a 1-mg intravenous loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1 month. A concurrent prospective cohort of 40 patients without previous SVD, who did not participate in the study and underwent pneumonectomy or EPP without prophylaxis, served as a comparison group for SVD occurrence. Serial Doppler echocardiograms were performed to assess cardiac function and all patients were continuously monitored with Holter recorders for 3 days. Data were analyzed by intent-to-treat. Results. In patients undergoing standard or intrapericardial pneumonectomy, diltiazem prevented the overall incidence of postoperative SVD when compared with digoxin, 0 of 21 patients versus 8 of 25 patients respectively, p p = 0.09. Digoxin-treated patients had a similar incidence of all SVD (31%) as concurrent controls (11 of 40 patients [28%]). The two treated groups did not differ in right or left atrial size, left ventricular ejection fraction, or right heart pressure. When all patients were combined, those in whom SVD developed were significantly older (65 ± 12 years versus 55 ± 11 years, p = 0.004) and had a longer median hospital stay (9 versus 6 days, p = 0.03), when compared with those in whom SVD did not develop, respectively. The subset of patients undergoing EPP had a greater incidence of atrial fibrillation and electrocardiographic changes suggestive of postoperative pericarditis than all other pneumonectomy patients. Conclusions. Diltiazem was both safe and more effective than digoxin in reducing the overall incidence of SVD after standard or intrapericardial pneumonectomy. Digoxin therapy had no effect on the incidence of postoperative SVD and is not recommended for prophylaxis of SVD. Dysrhythmias after pneumonectomy or EPP occur in older patients and are associated with a greater length of hospital stay.

The optimal treatment of stage III a/b non–small cell lung cancer continues to evolve. Depending on the specific clinical situation, surgical resection and/or radiation therapy may be utilized with or without concominant chemotherapy. Because of the heterogeneity of this disease, there can be no one uniform approach to treatment. Approximately 10 years ago, the American Joint Committee on Cancer Staging (AJCC) and International Union Against Cancer (UICC) divided stage III lung cancer into two distinct divisions 34 : one potentially surgically approachable (stage IIIa), and the other usually treated by nonoperative means (stage IIIb). In this international classification, stage IIIa included those patients with tumors designated T3 by virtue of involvement of potentially resectable structures, such as the adjacent chest wall, diaphragm, pericardium, or proximal airways. The presence of involved ipsilateral mediastinal or subcarinal lymph nodes (N2) also placed tumors into this category. Stage IIIb are those tumors designated T4 by virtue of involvement of usually unresectable structures, such as the trachea, great vessels, and vertebral body, or with a malignant pleural effusion. Additionally, tumors with involvement of contralateral mediastinal or supraclavicular lymph nodes (N3) are included in this subgroup. Although improved prognostic ability was gained by this subdivision of stage III disease, with stage IIIa associated with a better prognosis than stage IIIb, 34 heterogeneity within these subdivisions remains. For example, a small peripheral lesion with isolated chest wall involvement (T3N0), and a larger lesion with chest wall and mediastinal nodal involvement (T3N2), are both grouped under stage IIIa. Despite having the same stage of disease, a patient with the former should fare better than a patient with the latter, more advanced lesion. Thus, careful consideration of the specific tumor (T), node (N), and metastatic (M) characteristics of a given patient are essential. In the new (1997) consideration of the staging system, T3N0-1 will be classified as stage IIb to indicate its more favorable prognosis. Accurate staging of lung cancer is essential, because the selection of treatment approach is T and N dependent. 35 Traditionally, with the exception of T3N0 tumors, most stage IIIa and IIIb lesions have been treated with external beam radiation therapy, with 5-year survival rates of less than 10%. 11 Multimodality treatment approaches, however, have shown definite promise, especially for N2 and T3 disease, and they are the subject of this treatise.

Background. The accurate preoperative staging of lung cancer remains an essential element in its proper treatment. In most centers, N3 disease contraindicates an operative approach, despite the advent of combined modality therapy. Although it is used to confirm palpable supraclavicular disease, routine scalene lymph node biopsy to stage nonpalpable disease has been abandoned. Methods. From January 1991 to July 1995, 408 cervical mediastinoscopies were performed by a single surgeon for the staging of lung cancer. In those patients eligible for induction therapy, when N2 or N3 disease was strongly suspected or identified, ipsilateral scalene lymph node biopsy was performed through the same cervical incision using the mediastinoscope to reach the scalene fat pad. Results. Eighty-one patients underwent this additional staging procedure. There was minimal morbidity and no deaths. Of these 81 fully staged patients, primary tumor histology was non-small cell in 95.1%. Thirty-nine patients were staged as N2 after standard mediastinoscopy. Of these, 6 (15.4%) harbored occult nonpalpable supraclavicular lymph node disease as well. Nineteen patients were staged as N3-contralateral after standard mediastinoscopy. Of these, 13 (68.4%) had occult supraclavicular disease as well. Of all 58 patients with superior mediastinal nodal involvement identified by standard mediastinoscopy, 19 (32.8%) also harbored occult scalene lymph node disease, rendering them ineligible for our induction therapy protocols. Scalene positive primary tumors were all centrally located (visualizable by flexible bronchoscopy) (19 of 19) and were uniformly of nonsquamous origin. Conclusions. We believe that this technique is a valuable extension to standard cervical mediastinoscopy and can be used in N2 or N3 staged patients with central, nonsquamous tumors before considering a combined modality therapeutic approach that includes operation. Through its use, more accurate staging before initiation of therapy and elimination of those patients who may derive no benefit from an aggressive surgical approach may be possible.

Patients with unilateral vocal cord paralysis from intrathoracic malignancies may have significant dysfunctions of speech, swallowing, ventilation, and effective coughing as a result of inadequate compensation of the nonparalyzed cord. In patients with already compromised pulmonary function, aspiration can be a life-threatening event. Sixty-three patients with intrathoracic malignancies required surgical correction of vocal cord paralysis. Primary pathology included lung cancer (49), esophageal cancer (nine), and miscellaneous tumors (five). Symptoms included hoarseness (62), dyspnea (21), aspiration (26), weight loss (19), dysphagia (14), and pneumonia (14). The surgical procedures included medial displacement of the vocal cord with silicone elastomer (48), temporary Gelfoam injection (seven), and Teflon (polytetrafluoroethylene) injection (eight) to move the affected cord to a medial position. In 11 patients, the operation was performed in the acute postoperative setting to improve pulmonary toilet. Symptomatic improvement was noted in the following proportions of affected patients: hoarseness, 92%; dyspnea, 90%; dysphagia, 93%; aspiration, 92%; pneumonia, 93%; and weight loss, 47%. Overall success rate of the intervention was 57 of 63 patients (90%). All 11 patients treated in the acute setting had immediate improvement. A variety of complications occurred in 17% of patients. Surgical management of vocal cord paralysis in patients with intrathoracic malignancies prevents life-threatening pulmonary complications in the acute postoperative setting. In chronic situations, it provides patients with improved speech, swallowing, and pulmonary function, resulting in improved quality of life, even for patients not cured of their disease. (J T HORAC CARDIOVASC SURG 1996;111:334-41)

Background. Despite complete surgical excision, malignant thymomas often recur with resultant death. We reviewed our series to determine which factors independently predict survival after surgical resection. Methods. A retrospective analysis of patients operated on for thymoma between 1949 and 1993 at Memorial Sloan-Kettering Cancer Center was performed. Clinical data were collected from chart review. Only patients with a pathology report confirming the diagnosis of thymoma were included in this analysis. Kaplan-Meier survival curves were generated and comparisons of survival analyzed by log rank test. Multivariate analysis was performed by the Cox proportional hazards model. Results. One hundred eighteen patients with thymoma underwent operation. There were 86 complete resections (73%), 18 partial resections (15%), and 14 biopsies (12%). By Masaoka staging, 25 patients were stage I (21%), 41 stage II (35%), 43 stage III (36%), and 9 stage IVa (8%). Overall survival was 77% at 5 years and 55% at 10 years. Tumor recurred in 25 (29%) of 86 completely resected thymomas. Stage of disease ( p = 0.03) was the only independent prognostic factor affecting recurrence. By multivariate analysis, stage ( p = 0.003), tumor size ( p = 0.0001), histology ( p = 0.004), and extent of surgical resection ( p = 0.0006) were independent predictors of long-term survival. Conclusions. Patients with stage I disease require no further therapy after complete surgical resection. Neoadjuvant therapy should be considered for patients with large tumors and invasive disease.

Background. It has been reported that limited resection (segment or wedge) is equivalent to lobectomy in the management of early stage (T1–2 N0) non-small cell lung cancer. Methods. A prospective, multiinstitutional randomized trial was instituted comparing limited resection with lobectomy for patients with peripheral T1 N0 non-small cell lung cancer documented at operation. Analysis included locoregional and distant recurrence rates, 5-year survival rates, perioperative morbidity and mortality, and late pulmonary function assessment. Results. There were 276 patients randomized, with 247 patients eligible for analysis. There were no significant differences for all stratification variables, selected prognostic factors, perioperative morbidity, mortality, or late pulmonary function. In patients undergoing limited resection, there was an observed 75% increase in recurrence rates ( p = 0.02, one-sided) attributable to an observed tripling of the local recurrence rate ( p = 0.008 two-sided), an observed 30% increase in overall death rate ( p = 0.08, one-sided), and an observed 50% increase in death with cancer rate ( p = 0.09, one-sided) compared to patients undergoing lobectomy ( p = 0.10, one-sided was the predefined threshold for statistical significance for this equivalency study). Conclusions. Compared with lobectomy, limited pulmonary resection does not confer improved perioperative morbidity, mortality, or late postoperative pulmonary function. Because of the higher death rate and locoregional recurrence rate associated with limited resection, lobectomy still must be considered the surgical procedure of choice for patients with peripheral T1 N0 non-small cell lung cancer.

The use of preoperative chemotherapy with mitomycin, vinblastine and cisplatin (MVP) has led to improved complete resection rates and survival in Stage IIIA non-small cell lung cancer with bulky, ipsilateral, mediastinal lymph node metastases (Clinical N2 disease). The addition of preoperative irradiation has also been explored with results not substantially different from preoperative cisplatin-based chemotherapy alone. While preoperative chemotherapy has been shown to be feasible, the toxicity of both the chemotherapy and the subsequent resection is of concern with an overall treatment-related mortality of nearly 8%. The careful selection of patients, swift management of neutropenia, and meticulous perioperative pulmonary care has the potential to reduce the mortality from multimodality therapy. Having shown survival benefit in multiple single-institution and randomized trials, induction chemotherapy followed by surgery or irradiation is now the treatment of choice for patients with Stage IIIA non-small cell lung cancer with mediastinal lymph node metastases.

Retrospective analyses have shown that, following surgical resection, patients with early-stage small cell lung cancer have a survival rate comparable to that seen with non-small cell lung cancer, especially if combined modality therapy is used. Surgery has been employed in three specific instances: primary surgery followed by postoperative chemotherapy and, when indicated, mediastinal irradiation for tumors presenting as peripheral nodules; multimodality therapy including induction chemotherapy followed by surgery; and radiotherapy in "resectable", very limited disease and "salvage surgery" for patients with limited disease previously treated, recurring at the primary site. The results of such surgery in very selected patients yields the best reported results in the treatment of small cell lung cancer. These approaches are worthy of further study.

From 1973 to 1985, 598 patients underwent resection for stage I non-small-cell lung cancer. There were 291 T1 lesions and 307 T2 lesions. The male/female ratio was 1.9:1. The histologic type was squamous carcinoma in 233 and nonsquamous carcinoma in 365. Lobectomy was performed in 511 patients (85%), pneumonectomy in 25 (4%), and wedge resection or segmentectomy in 62 (11%). A mediastinal lymph node dissection was carried out in 560 patients (94%) and no lymph node dissection in 38 (6%). Fourteen postoperative deaths occurred (2.3%). Ninety-nine percent of the patients were observed for a minimum of 5 years or until death with an overall median follow-up of 91 months. The overall 5- and 10-year survivals (Kaplan-Meier) were 75% and 67%, respectively. Survival in patients with T1 N0 tumors was 82% at 5 years and 74% at 10 years compared with 68% at 5 years and 60% at 10 years for patients with T2 tumors ( p < 0.0004). The overall incidence of recurrence was 27% (local or regional 7%, systemic 20%) and was not influenced by histologic type. Second primary cancers developed in 206 patients (34%). Of these, 70 (34%) were second primary lung cancers. Despite complete resection, 31 of 62 patients (50%) who had wedge resection or segmentectomy had recurrence. Five- and 10-year survivals after wedge resection or segmentectomy were 59% and 35%, respectively, significantly less than survivals of those undergoing lobectomy (5 years, 77%; 10 years, 70%). The 5- and 10-year survivals in the 38 patients who had no lymph node dissection were reduced to 59% and 32%, respectively. Apart from the favorable prognosis observed in this group of patients, three facts emerge as significant: (1) Systematic lymph node dissection is necessary to ensure that the disease is accurately staged; (2) lesser resections (wedge/segment) result in high recurrence rates and reduced survival regardless of histologic type; and (3) second primary lung cancers are prevalent in long-term survivors. (J Thorac Cardiovasc Surg 1995;109:120-9)

The results of surgical treatment were analyzed for 102 patients with non-small cell lung cancer invading the mediastinum by direct extension (T3 and T4), but those who had N2 disease were excluded to eliminate the adverse prognostic effect of this nodal subset. The histologic type was squamous cell carcinoma in 55 patients, adenocarcinoma in 40, and large cell carcinoma in 7. There were 58 T3 tumors invading the mediastinal pleura or fat, phrenic nerve, vagus nerve, pericardium, or pulmonary vessels and 44 T4 lesions invading the aorta, vena cava, esophagus, trachea, spine, or atrium. Resection included lobectomy (33 patients), pneumonectomy (32 patients), and limited resection (6 patients). Complete resection was possible in 46 patients and incomplete or no resection was possible in 56. The interstitial implantation of radioactive sources to control residual tumor also was undertaken in 43 patients. The operative mortality was 6%. The overall survival (Kaplan-Meier) was 19% at 5 years (median survival time, 18 months). Factors found to significantly affect survival were complete resectability and the histologic type. With complete resection, the 5-year survival was 30% ( p = 0.005). The 5-year survival in patients with adenocarcinoma or large-cell carcinoma was 30%, compared with 14% in patients with squamous cell carcinoma ( p = 0.002). The extent of mediastinal involvement (T3 versus T4) influenced resectability and survival, and this approached statistical significance ( p = 0.055). We conclude that most patients with non-small cell carcinoma and mediastinal invasion do poorly with primary surgical treatment.

PURPOSE This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy. PATIENTS AND METHODS Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first. RESULTS Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients). CONCLUSION This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control.

Background. Extragonadal germ cell tumors (EGCT) represent only 2–5% of adult germ cell malignancies. Because they are rare and biologically distinct from testis cancer, their natural history and optimal management continue to be defined. The clinical characteristics, treatment, and outcome of 40 patients are presented here. Methods. Patients were identified through the medical records of four University of Toronto teaching hospitals. All patients were treated in specialized oncology units between 1978 and 1993. Results. Thirty–seven males and three females age 16–54 years (median, 24 years) with primary mediastinal (n = 24), retroperitoneal (n = 7), CNS (n = 7), and widespread (n = 2) EGCT were identified. Eight of nine patients (88%) with mediastinal seminoma are alive with no evidence of disease (NED) at 4–132 months (median, 45 months). After combined modality therapy, only 8 of 15 patients (53%) with mediastinal nonseminomas achieved complete remission (CR); 1 experienced relapse and died, resulting in 7 of 15 patients (47%) with NED at 45–86 months (median, 70 months). All three patients with retroperitoneal seminomas achieved CR and all have NED at 77,103, and 120 months, respectively. Two of four patients with retroperitoneal nonseminomas have died, and the other two are alive at 36 and 54 months. Seven patients with CNS germinomas (seminoma) achieved CR after craniospinal radiation therapy, but one subsequently died after local relapse. The overall survival rate was 87% (median, 74 months). One patient with widespread choriocarcinoma died and the other achieved CR. Conclusions. Regardless of site of presentation, ex–tragonadal seminomas have a greater than 80% 5–year disease–free survival rate. Mediastinal nonseminomas are biologically distinct, with a poorer prognosis. Treated with cisplatin–based chemotherapy followed by aggressive resection, approximately 50% of patients survive. CNS seminomas have a good prognosis. Nonseminomas of the CNS are extremely rare and were not represented in the current series. These findings concur with other reported series.

Videothoracoscopy has rapidly become a popular procedure, but its technical feasibility has been emphasized without critically evaluating its role in the management of thoracic disease. To assess the value of videothoracoscopy in the diagnosis and staging of the cancer patient and to determine if it has added to our previous standard approach of thoracoscopy performed with a mediastinoscope without video, we established a prospective database when we initiated videothoracoscopy in January 1992.Patients were offered videothoracoscopy as an alternative to thoracotomy only if other standard approaches (e.g., needle biopsy, mediastinoscopy) were inadequate to diagnose or stage cancer or to restage patients after therapy. Parameters entered and analyzed in a prospective database were patient name; age; sex; past history; indications for videothoracoscopy; procedure type; surgical technique; whether conversion to thoracotomy was necessary, and if so, why; complications; and pathology. A complete case list of thoracoscopies performed in 1991 before videothoracoscopy was available provided historical comparison.From January 1 to December 31, 1991, 82 patients underwent thoracoscopy using a mediastinoscope for diagnosis and therapy of pleural disease. From January 1 to July 31, 1992, 160 patients (male:female = 81:79; mean age 56 years) had videothoracoscopy; 72 of 160 patients (44%) had procedures that previously would have required thoracotomy: 69 lung wedge resections, one pericardial window, one pleurectomy, one mediastinal node sampling. No major resectional procedures (e.g., lobectomy, esophagectomy) were performed by videothoracoscopy. Twenty-two percent of all patients (35 of 160), and 23% of wedge resection patients (16 of 69) required conversion to thoracotomy because videothoracoscopy was inadequate for diagnosis or staging. Reasons for conversion (multiple reasons in five patients) included further resection required in 23 patients; inability to evaluate lesion in 11; adhesions in five; and inability to tolerate one lung ventilation in two. The chest tube was in place postoperatively for a mean of 2.3 days. Thirty-day postoperative complications included ventilation for48 h in one patient; prolonged air leak in one; pneumonia in one; arrhythmia in one; and death from progressive disease in two.Although the role of videothoracoscopy in the treatment of primary thoracic malignancies and pulmonary metastases is still undefined, this early experience indicates that videothoracoscopy often enhances the ability to diagnose and stage patients by obviating thoracotomy.

Video-assisted thoracoscopic surgery is emerging as a valuable tool in the investigation and management of thoracic neoplasms, including those involving the pleura, lung, and mediastinum with the e...

We designed a prospective study to evaluate the accuracy of magnetic resonance imaging in distinguishing a benign from a malignant adrenal mass in patients with otherwise operable non-small-cell lung cancer. Methods: Potentially operable non-small-cell lung cancer was prospectively staged. If a unilateral adrenal mass was found by computed tomographic scanning, respiratory compensated and cardiac gated thin section magnetic resonance imaging of the adrenal glands was done. One radiologist interpreted the magnetic resonance imaging scan blinded and, on the basis of the relative signal strengths of the T1- and T2-weighted images, judged whether the adrenal mass was benign or malignant. The patients then underwent a percutaneous needle biopsy of the adrenal mass, if technically feasible. If the result of the needle biopsy was nondiagnostic or if the biopsy was not feasible, an adrenalectomy through a posterior approach was performed. Results: Twenty-seven patients with a unilateral adrenal mass entered the study—11 men and 16 women whose ages ranged from 42 to 75 years (median 58 years). Four patients had epidermoid and 23 adenocarcinoma of the lung. The clinical locoregional stage was I in 9, II in 1, IIIA in 16, and IIIB in 1. Twenty-five completed the magnetic resonance imaging procedure. Five adrenal masses (19%) were metastatic non-small-cell lung cancer (adenocarcinoma = 4, epidermoid=1); 22 masses (81 %) were benign (adenoma = 20, hyperplasia=2). There were no significant differences in age, sex, histologic type, or locoregional stage between those with a benign versus a malignant mass. However, the malignant masses were significantly larger (3.8 ± 1.9 cm; range 2.5 to 7.1; median 3.1) than the benign masses (2.0 ± 0.4 cm, range 1.2 to 2.8; median 2.0) ( p n = 25), the technique correctly predicted a malignant mass in the four patients with a histologically confirmed metastasis from non-small-cell lung cancer. However, among the 21 histologically benign masses, the magnetic resonance imaging was interpreted as benign in 5, malignant in 14, and indeterminate in 2. Therefore, although the false-negative rate was 0 %, the false-positive rate was 67%. Conclusion: Most adrenal masses in patients with otherwise operable non-small-cell lung cancer are benign. Currently available magnetic resonance imaging methods cannot replace biopsy.

From 1953 to 1992, 25 patients were surgically treated for bronchial carcinoids with metastases to regional lymph nodes (N1 or N2). The tumors were located centrally, involving main or lobar bronchi in 12 patients and were peripheral in 13. Histologically, 12 of the carcinoids were classified as typical and 13 as atypical (neuroendocrine carcinoma). Pneumonectomy was performed in 11 patients, sleeve lobectomy in one, lobectomy in seven and bilobectomy in six. A formal mediastinal lymph node dissection was done in 20 patients. At final staging, 10 had N1 disease and 15 had N2. No adjuvant treatment was given to the 10 patients with N1 disease. External radiation therapy was given after the operation to 9 of 15 patients with N2 disease. The overall 5-year survival (Kaplan-Meier) was 75% (median 62 months). No difference in survival was found between patients with N1 or N2 disease. However, survival and recurrence rate differed between typical and atypical carcinoids. In typical carcinoids, the 5-year survival was 92% and, in atypical carcinoids, it was 60% ( p = 0.02). We conclude that complete resection for bronchial carcinoids results in long-term survival despite the presence of regional lymph node metastases. Recurrence appears to depend more on cell type than nodal status. Postoperative radiation therapy does not appear to be beneficial. (J THORAC CARDIOVASC SURG 1994;107:1-7)

Computed tomographic scanning has improved the noninvasive staging of lung cancer but has the deficiency of not distinguishing benign from malignant lesions. This prospective trial evaluated the usefulness of a new radiolabeled monoclonal antibody, NR-LU-10, as an adjunct to computed tomography by assessing its clinical applicability and accuracy in detecting malignancy in primary lung tumors and mediastinal nodes. NR-LU-10 is a technetium 99m–labeled Fab fragment of a murine immunoglobulin G2b monoclonal antibody that recognizes a 40 kD glycoprotein expressed in lung and other epithelial cancers. Methods: (1) Patients with potentially resectable non-small-cell lung cancer were eligible; (2) all patients had computed tomographic scans of the chest; (3) whole body and single photon emission computed tomographic imaging were performed 14 to 17 hours after intravenous infusion of 20 to 30 mCi of NR-LU-10; (4) subsequent mediastinoscopy or thoracotomy with complete mediastinal nodal mapping provided pathologic correlation. Results: Twenty-four patients were entered, 14 men and 10 women. No allergic reactions or other adverse effects were seen. Interference from a prior ventilation-perfusion scan precluded adequate imaging in 1 patient, but high-quality images were obtained in the other 23 patients. The 22 primary malignant tumors all had uptake and there was no uptake in 1 lung nodule found to be benign. In 21 patients who had surgical correlation of mediastinal nodal involvement, NR-LU-10 was false-positive in 5 and false-negative in 1; results of computed tomography were false-positive in 6 and false-negative in 1. In this preliminary study, NR-LU-10 antibody scanning was safe and easily performed, it produced high-quality images of the lung and mediastinum, and it was accurate in detecting primary non-small-cell lung cancers. Further evaluation of its value in staging the mediastinum is needed, in particular, its role as an adjunct to computed tomography to help distinguish benign from malignant lesions.

The results of surgery in stage IIIA (N2) disease has prompted Phase II studies examining the role of induction chemoeradiotherapy prior to surgery. Early results suggest a prolonged median survival time and somewhat improved long-term survival for patients treated in this fashion. Surgeons must be involved in pretherapy surgical staging and assessment of the patients for potential resection following induction treatment. Although surgery is more difficult at this stage of disease, especially after induction treatment, morbidity and mortality results appear acceptable.

From 1984 to 1991, 136 patients with histologically confirmed non-small cell lung cancer and stage IIIa (N2) disease received two to three cycles of MVP (mitomycin + vindesine or vinblastine + high-dose cisplatin) chemotherapy. All patients had clinical N2 disease, defined as bulky mediastinal lymph node metastases or multiple levels of lymph node involvement in the ipsilateral mediastinum or subcarinal space on chest roentgenograms, computed tomographic scans, or mediastinoscopy. The overall major response rate to chemotherapy was 77% (105/136). Thirteen patients had a complete response and 92 patients had a partial but major response (> 50%). The overall complete resection rate was 65% (89/136) with a complete resection rate of 78% (82/105) in patients with a major response to chemotherapy. There was no histologic evidence of tumor in the resected specimens of 19 patients. The overall survival was 28% at 3 years and 17% at 5 years (median, 19 months). For patients who had complete resection, the median survival was 27 months and the 3-year and 5-year survivals were 41% and 26%, respectively. There were seven treatment-related deaths, five of which were postoperative deaths. To date, 33 patients, all of whom had complete resection, have had no recurrence after treatment. These results demonstrate that (1) preoperative chemotherapy with MVP produces high response rates in stage IIIa (N2) disease, (2) high complete resection rates occur after response to chemotherapy, and (3) survival is longest in patients who have a complete resection after major response to chemotherapy.

Determination of the eventual role of aggressive, multimodality therapy in the treatment of locally advanced lung cancer awaits the results of these and other trials. Ultimately, however, it is hoped that these studies will lead to improved prospects for the many patients who present with lung cancer that was previously considered inoperable.

The role of surgery for small cell lung cancer (SCLC) has been hotly contested over the past 20 years. Despite misgivings promoted by the failure of surgery to control disease as documented by a report of the British Medical Research Council in 1969 [1], surgeons continued to operate on SCLC. It soon became apparent that in stage I (T1N0, T2N0) disease, surgical therapy alone can provide curative treatment in up to 50% of patients. With the addition of postoperative chemotherapy, it appears that in this early stage of disease, even better long-term survival may be possible [2].

The 5-year survival rates for patients undergoing a potentially curative surgical resection for pre-operatively identified stage 3A N2 non-small cell lung cancer (NSCLC) vary from 2–13%. In an attempt to improve the curative potential of surgery, 39 patients with mediastinoscopy stage 3A unresectable N2 NSCLC received induction chemotherapy with 2 cycles of mitomycin-C, vindesine and cisplatin (MVP). Responding patients underwent thoracotomy for resection and 2 further courses of MVP. The overall response rate was 64% ( 25 39 ) with 3 complete and 22 partial responses. 22 patients were resected which included a radical mediastinal node dissection. 18 resections were complete and 4 were incomplete. Pathologically 3 patients (7.7%) had no tumor remaining. There were 2 post-op deaths secondary to a BP fistula. In addition to GI and neurologic side effects, toxicity of chemotherapy included mitomycin pulmonary toxicity in 2 patients and 4 septic deaths. 28 patients have died, 20 with recurrent or progressive disease. Of the 18 patients completely resected, 8 have recurred with a median time to recurrence of 20.6 months. Sites of recurrence include 2 loco-regional, 5 distant (2 in brain) and 1 both. Median survival of the entire 39 patients is 18.6 months with a 3-year survival of 26%. The median survival for those patients completely resected is 29.7 months with a 3-year survival of 40%. These findings suggest that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC, and although the median survival appears to be prolonged, the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a Phase III randomized trial comparing it to other treatment modalities.