Management of elderly patients with NSCLC; updated expert's opinion paper: EORTC Elderly Task Force, Lung Cancer Group and International Society for Geriatric Oncology.

Non-small-cell lung cancer (NSCLC) is a very common disease in the elderly population and its incidence in this particular population is expected to increase further, because of the ageing of the Western population. Despite this, limited data are available for the treatment of these patients and, therefore, the development of evidence-based treatment recommendations is challenging. In 2010, European Organization for Research and Treatment of Cancer (EORTC) took an initiative in collaboration with International Society of Geriatric Oncology (SIOG) and created an experts panel that provided an experts' opinion consensus paper for the management of elderly NSCLC patients. Since this publication, important new data are available and EORTC and SIOG recommended to update the 2010 recommendations. Besides recommendations for surgery, adjuvant chemotherapy and radiotherapy, treatment of locally advanced and metastatic disease, recommendations were expanded, to include data on patient preferences and geriatric assessment.

A model to assess interventions to improve collateral blood flow: continuous administration of agents into the left coronary artery in dogs.

OBJECTIVE: The aim was to develop an experimental model in which angiogenic growth factor(s) could be targeted locally to enhance myocardial collateral formation. A preparation was developed in which agents could be infused selectively into the left main coronary artery on a chronic basis to assess the potential of acidic fibroblast growth factor (FGF) to improve collateral blood flow. METHODS: Ameroid constrictors were placed on the left circumflex coronary artery of mixed hounds. Five weeks after ameroid placement, the artery was ligated and transected at the point of ameroid occlusion; a catheter was inserted and passed retrogradely into the left main coronary artery. The catheter was connected to an implantable infusion pump that provided continuous intracoronary drug infusion for 4 weeks. Dogs were randomised to receive acidic FGF with heparin (30 micrograms.h-1 and 30 IU.h-1, respectively, n = 16) or heparin alone (30 IU.h-1, n = 14). Regional myocardial blood flow was determined in the conscious state at the beginning and end of treatment. RESULTS: There were no deaths or important surgical complications related to the establishment of the coronary artery infusions. During the treatment interval (5-9 weeks after ameroid placement) the ratio of maximum ischaemic zone/normal zone blood flow increased from 0.39(SD 0.10) to 0.50(0.11) (p < 0.01) in dogs treated with acidic FGF plus heparin; however, similar improvement was noted in dogs treated with heparin alone. Ischaemic zone and normal zone vascular density was also equivalent in the two groups. CONCLUSIONS: This preparation makes possible the chronic intracoronary administration of agents which may promote myocardial angiogenesis, and allows assessment of collateral blood flow before and after treatment. As given in this investigation, acidic FGF had no demonstrable effect on collateral blood flow; however, this model may facilitate the identification of agents that do enhance myocardial collateral formation.

The surgical management of elderly cancer patients; recommendations of the SIOG surgical task force.

Although cancer in the elderly is extremely common, few health professionals in oncology are familiar with caring for series of oncogeriatric patients. Surgery is at present the first choice, but is frequently delivered suboptimally: under-treatment is justified by concerns about unsustainable toxicity, whilst over-treatment is explained by the lack of knowledge in optimising preoperative risk assessment. This article summarises the point of view of the Surgical Task Force @ SIOG (International Society for Geriatric Oncology), pointing out differences from, and similarities to, the younger cohorts of cancer patients, and highlighting the latest updates and trends specifically related to senior cancer patients.

Thoracoscopic staging and surgical therapy for esophageal cancer.

Esophageal cancer continues to be a major health problem with an associated poor prognosis. New technology is being applied to the staging of this cancer. The new staging system requires assessment of depth of wall penetration and lymph node status prior to resection. To determine penetration and node status with a high degree of accuracy generally requires some combination of chemotherapy, magnetic resonance imaging, endoesophageal ultrasound, and/or surgical staging. Several variables need to be considered in planning the surgical approach to the patient with esophageal cancer: the intent of the surgeon to either cure or palliate, the anatomic location of the tumor, and the method of reconstruction. Surgery is optimal for localized esophageal cancer. Neoadjuvant chemoradiation has increased survival in specific subgroups. Phase 2 trials have shown the safety and efficacy of chemoradiation. Randomized multi-institutional trials are needed to verify the encouraging results of recent phase 2 trials.

Mesothelioma and radical multimodality therapy: who benefits?

The incidence of malignant pleural mesothelioma is increasing. Untreated, patients with this disease experience a rapid and horrendous clinical decline. Surgery plays a role in the diagnosis, staging, and treatment of this malignancy. Surgery, chemotherapy, and radiotherapy alone have been unable to achieve major improvements in survival for most patients. More recent phase II trials suggest that surgery, at one time a purely palliative approach, may have a potentially curative role when used in combination with chemotherapy and radiotherapy.

Esophagectomy after induction chemoradiation.

The definition of a standard therapy for resectable esophageal cancer remains a clinical controversy. In the past decade, a variety of strategies have been developed in an attempt to improve local control and decrease the all too common problem of distant metastases. Preoperative treatment with radiotherapy or chemotherapy has been proved to be feasible, although neither strategy has resulted in improved survival rates. More recently, concurrent, neoadjuvant chemoradiation has been utilized with encouraging pathologic responses. Equally important is the recognition that such aggressive therapy does not lead to worse surgical outcomes. The evidence for the safety, feasibility, and efficacy of induction therapy followed by esophagectomy is presented in the context of developing a rational methodology to allow for the ongoing modification of standards of care in the management of this difficult disease.

Video-assisted thoracic surgery in the elderly. A review of 307 cases.

STUDY OBJECTIVE: The objective of the study was to investigate the impact of video-assisted thoracic surgery (VATS) on age-related morbidity and mortality for thoracic surgical procedures. DESIGN: Prospective data were collected on 896 consecutive VATS procedures from July 1991 to June 1994. Daily in-hospital, postoperative data collection by a full-time thoracic surgical nurse and postdischarge follow-up in a thoracic surgery clinic at 1 and 6 weeks were done. PATIENTS: On 296 patients aged 65 or older, 307 procedures were performed. One hundred nine procedures were performed on patients between 65 and 69 years, 110 on patients between 70 and 74 years, 55 on patients between 75 and 79 years, and 33 on those between 80 and 90 years. MEASUREMENTS AND RESULTS: The population was divided into four cohorts of 5-year age spans for analysis. Comparison was made with Fisher's Exact Test. Overall, 61% of the 307 procedures were for pulmonary disease. There were 32 anatomic lung resections (VATS lobectomies or segmentectomies), 156 extra-anatomic lung resections (thoracoscopic wedge or bullectomy), 78 procedures for pleural disease (25%), 27 mediastinal dissections (9%), and 14 pericardial windows (5%). There was a trend toward a lower mean FEV1 with increasing age. There were 3 deaths; overall mortality was less than 1%. There were 4 conversions to open thoracotomy (1%). Complications occurred with 45 procedures (15% morbidity). Twenty-two operations (7%) were associated with major complications adding to the length of stay and 27 procedures (9%) had minor complications. Median length of stay after VATS was 4 days for patients aged 65 to 79 years and 5 days for those aged 80 to 90 years. Morbidity and mortality were unrelated to age. CONCLUSIONS: The 30-day operative mortality is superior to previous reports of standard thoracotomy. Morbidity is low and length of hospital stay appears improved. VATS techniques may be safer than open thoracotomy in the aged. Age alone should not be a contraindication to operative intervention.

New surgical options for elderly lung cancer patients.

To understand the size of the aging population in the United States, the imminent need to include the elderly in clinical studies on lung cancer, and the safe potential of video-assisted thoracic surgery, and to change awareness of the elderly's need for and ability to undergo treatment for lung cancer, clinical studies of video-assisted thoracic surgery in patients > or = 70 years of age are presented. The elderly are a fast-growing part of the American population who are at high risk for lung cancer and should be included in clinical studies. Age alone should not be a contradiction to thoracic surgical interventions when video thoracoscopy is performed as treatment.

Management of the solitary pulmonary nodule: role of thoracoscopy in diagnosis and therapy.

OBJECTIVES: The solitary pulmonary nodule remains a common clinical problem. The essential question is whether the lesion is malignant or not. This discussion presents the clinical practice and looks at the problem. DESIGN: Didactic. SETTING: Academic tertiary-care hospital. PATIENTS: Prospective thoracic database. INTERVENTIONS: Minimally invasive technique. RESULTS: The workup and treatment of the solitary pulmonary nodule is presented with particular emphasis on the role of minimally invasive techniques. A small single-institution series is referenced. CONCLUSIONS: The approach is safe and highly effective in diagnosing and often in treating solitary pulmonary nodules.

Sequential thoracic metastasectomy prolongs survival by re-establishing local control within the chest.

OBJECTIVE: The value of sequential thoracic metastasectomies is unknown. We evaluate repeat metastasectomy for limited recurrences within the thorax. METHODS: From July 1988 to September 1998, 54 patients underwent 2 to 6 separate sequential procedures to excise metastases after recurrence isolated to the thorax. Kaplan-Meier survival and Cox modeling determined prognostic variables. RESULTS: Thirty-three men and 21 women, 22 to 76 years underwent 2 (100%, n = 54), 3 (50%), 4 (22%), or 5 to 6 (11%) metastasectomies. Fifty-four percent of patients had carcinoma, 35% sarcoma, 9% germ cell, and 2% melanoma. There were no operative deaths; all late deaths occurred from cancer. Median follow-up was 48 months. Cumulative 5-year survival from the second procedure was 57%. After the second, third, fourth, and fifth procedures, respectively, permanent control was achieved in 15 (27%) of 54 patients, 5 (19%) of 27, 1 (8%) of 12, and 0 of 7. Recurrence amenable to additional surgery occurred in 27 (50%) of 54, 12 (44%) of 27, 6 (50%) of 12, and 1 (17%) of 6. Mean hazard for the development of unresectable recurrence increased from 0.21 after the second procedure to 0.91 after the fifth procedure. The 5-year survival for the 27 patients undergoing only 2 metastasectomies was 60% (median not yet reached), 33% for the 15 patients undergoing only 3 metastasectomies (median 34.7 months), and 38% for the 12 patients undergoing 4 or more (median 45.6 months). From the time a recurrence was declared unresectable, patients had a 19% 2-year survival (median 8 months). CONCLUSIONS: Multiple attempts to re-establish intrathoracic control of metastatic disease is justified in carefully selected patients, but the magnitude of benefit decays with each subsequent attempt.

Surveillance transbronchial lung biopsies: implication for survival after lung transplantation.

OBJECTIVES: We wished to determine whether early rejection after lung transplantation as assessed by surveillance transbronchial biopsy predicts for survival. METHODS: Between 1990 and 1997, 96 consecutive patients had lung transplantation: 89 had a minimum 1-month follow-up. For 71 consecutive patients we have 1-year follow-up and for 69 patients we have the results of the first 3 biopsies. Cytomegalovirus status, bronchiolitis obliterans prevalence, and use of total lymphoid irradiation are noted. Biopsies were done at 1 week and 1, 3, and 6 months. Standard immunosuppression consisted of induction antilymphocyte globulin and high-dose methylprednisolone induction for 1 week and standard maintenance triple therapy. Acute rejection treatment was with pulse methylprednisolone. Bronchiolitis obliterans syndrome was treated with total lymphoid irradiation and a change to tacrolimus and mycophenolate. Blinded grading using International Society for Heart and Lung Transplantation classification was done retrospectively. RESULTS: Survival at 1 month and 1, 2, and 3 years for the 96-patient cohort with 1-year follow-up was 93%, 74%, 62%, and 56%. Survival was not significantly different for subsets with rejection on any combination of the first 3 biopsies (1/3, 2/3, 3/3) or absence of rejection on the first 3 biopsies. Ninety-one positive biopsy results were graded. Eighteen of 71 patients had one or more moderate or severe rejection episodes without survival difference relative to the others. There was no statistically significant association between acute rejection on the first 3 surveillance biopsy results and bronchiolitis obliterans. CONCLUSIONS: Intensive induction and maintenance immunotherapy with surveillance transbronchial biopsies and aggressive treatment of acute rejection is associated with a survival similar to that of patients without early acute rejection. This regimen appears to uncouple the association between early acute rejection and bronchiolitis obliterans. Further study may elucidate this mechanism.

Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients.

OBJECTIVES: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma. METHODS: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy. RESULTS: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05). CONCLUSIONS: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.

An historical perspective of multi-modality treatment for resectable non-small cell lung cancer.

We examine the origins of surgical therapy, radiotherapy, and chemotherapy as they were applied to lung cancer in the mid-portion of this century. Surgical therapy for lung cancer started in the 1930s with pneumonectomies. The prognostic significance of nodal metastases was soon recognized, and surgical staging procedures became an important part of patient workup. Radical radiotherapy for potential cure of lung cancer began in the 1950s with megavoltage linear accelerators. The first application of chemotherapy for lung cancer was the use of nitrogen mustards in the 1940s. Single modality surgical therapy has become the treatment of choice for Stages I and II non-small cell lung cancer, but 50% of clinical Stage I patients die of recurrent disease, and 70% of those recur outside the chest. Biologic markers may identify high risk subgroups of Stage I and II patients who may benefit from adjuvant chemo- or radiotherapy. Within the last decade, several single and multi-institutional Phase II trials and two single institution Phase III trials have reported improved survival in Stage IIIA patients treated with cisplatin-based neoadjuvant chemotherapy prior to surgical resection. These trials have reported high response and resectability rates, but at a substantial toxicity. A new standard of care for Stage IIIA disease has not been conclusively established.

Open-lung biopsy guides therapy in children.

BACKGROUND: Open-lung biopsy is uncommon in children. Modern indications and outcomes are unknown. METHODS: This is a retrospective review of 64 open-lung biopsies (58 patients) from 1976 to 1996. Open-lung biopsies were used to grade vasculopathy in 8 patients (12% of 64) with pulmonary hypertension and in 10 patients (16% of 64) with combined pulmonary hypertension and lung parenchymal disease. Forty-six biopsies (72%) were obtained to diagnose parenchymal disease. Comparisons were made between biopsies performed from 1976 to 1989 and from 1990 to 1996. RESULTS: In the period 1990 to 1996, there were significantly more infants (p = 0.03), comorbid disease (p = 0.009), extracorporeal membrane oxygenation support (p < 10(-4)), and ventilator dependence (p = 0.05) and significantly less immunocompromise (p = 0.04). A definitive diagnosis was made in 43 of 64 cases (67%) and altered workup in 63 of 64 cases (98%). No correlation existed between Heath-Edwards grade of microangiopathy and catheterization data. Definitive diagnosis was most strongly associated with a nonimmunocompromised patient (p < 10(-4)). Although only one death (1.5%) was related to open-lung biopsy, the procedure was associated with a 30% inhospital mortality rate and an 11% morbidity rate. Of the 19 deaths, 1 patient died from the procedure, 13 died from their diseases, and 5 had support withdrawn. Death was associated with preoperative ventilator dependence (p < 10(-4)) and extracorporeal membrane oxygenation (p = 0.007). CONCLUSIONS: Pediatric open-lung biopsy commonly alters the diagnostic workup (98%). It is recommended for children who have been supported for 2 weeks by extracorporeal membrane oxygenation and for those with combined pulmonary hypertension and parenchymal lung disease. It is less useful in immunocompromised children.

Thoracoscopic staging of esophageal cancer: a prospective, multiinstitutional trial. Cancer and Leukemia Group B Thoracic Surgeons.

BACKGROUND: Lymph node metastasis has been shown to be an important prognosticator in esophageal cancer. A prospective, multiinstitutional study of thoracoscopic lymph node staging in patients with biopsy-proven esophageal cancer was undertaken at University of Maryland, Medical University of South Carolina, and Brigham and Women's Hospital. METHODS: Forty-nine patients underwent thoracoscopic staging between September 1991 and August 1993. Five procedures were incomplete due to adhesions. Preoperative computed tomography, magnetic resonance imaging, esophageal ultrasound, and bronchoscopy were performed. After our initial experience with the left side of the chest, thoracoscopic staging was done through the right side of the chest unless specific indications dictated otherwise. Beginning in January 1993 routine laparoscopic/mini-laparotomy lympho node staging of the celiac axis was performed. RESULTS: Satisfactory thoracoscopic lymph node staging was achieved in 44 patients (95%). Of 33 patients undergoing esophageal resection, 29 were correctly staged (88%). Since initiating concomitant laparoscopic lymph node staging, we have correctly staged all of the last 9 patients with regard to celiac lymph nodes as well. Information regarding T status obtained at thoracoscopy was as follows: 3 patients were correctly "downstaged" to T3 despite preoperative noninvasive tests suggesting T4. In 2 patients thoracoscopy correctly predicted T4 invasion, whereas in 2 patients, thoracoscopy missed T4 lesions. CONCLUSIONS: Thoracoscopy is a valuable tool for staging intrathoracic tumors. Preoperative staging of esophageal cancer may allow better allocation of adjuvant therapy. This pilot study suggests that thoracoscopic staging can correctly predict thoracic lymph node status with high accuracy and aid in better defining T status.

Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival.

BACKGROUND: This study was undertaken to determine the predictive value of nodal status at resection in regards to long-term outcome of patients undergoing neoadjuvant therapy and resection for stage IIIA N2-positive non-small cell lung cancer (NSCLC). METHODS: We reviewed the medical records of all patients found on surgical staging to have N2-positive NSCLC and who underwent induction therapy followed by resection between 1988 and 1996 at our hospital. Complete follow-up information was examined utilizing Kaplan-Meier survival analysis and Cox proportional hazards multivariate analysis. RESULTS: One hundred three patients (59 men) with stage IIIA N2-positive NSCLC received neoadjuvant therapy before surgical resection. Preoperative therapy consisted of platinum-based chemotherapy (76), radiotherapy (18), or chemoradiation (9). Operations included pneumonectomy (38), bilobectomy (6), and lobectomy (59). There were four deaths and seven major complications. Eighty-five patients were followed until death. Median survival among 18 living patients is 60.9 months (range 29 to 121 months). Twenty-nine patients were downstaged to N0 and had 5-year survival of 35.8% (median survival 21.3 months). Seventy-four patients with persistent tumor in their lymph nodes (25 N1 and 49 N2) had significantly worse, 9%, 5-year survival, p = 0.023 (median survival 15.9 months). Other negative prognostic factors were adenocarcinoma and pneumonectomy. CONCLUSIONS: Patients with N2-positive NSCLC whose nodal disease is eradicated after neoadjuvant therapy and surgery enjoy significantly improved cancer-free survival. These data support surgical resection for patients downstaged by induction therapy; however, patients who are not downstaged do not benefit from surgical resection. Direct effort should be made to improve the accuracy of restaging before resection.

Transthoracic esophagectomy with radical mediastinal and abdominal lymph node dissection and cervical esophagogastrostomy for esophageal carcinoma.

BACKGROUND: Several techniques for esophageal resection have been reported. This study examines the morbidity, mortality, and early survival of patients after transthoracic esophagectomy for esophageal carcinoma using current staging techniques and neoadjuvant therapy. The technique includes right thoracotomy, laparotomy, and cervical esophagogastrostomy (total thoracic esophagectomy) with radical mediastinal and abdominal lymph node dissection. METHODS: Three hundred forty-two patients had surgery for esophageal carcinoma between 1989 and 2000 at our institution. Two hundred fifty consecutive patients had esophagectomy using this technique. Kaplan-Meier curves and univariate and multivariate analyses were performed by postsurgical pathologic stage. RESULTS: Median age was 62.7 years (31 to 86 years). Fifty-nine were female. Eighty-one percent (202) had induction chemotherapy (all patients with clinical T3/4 or N1). Early postoperative complications included recurrent laryngeal nerve injury (14% [35]), chylothorax (9%, [22]), and leak (8%, [19]). Median length of stay was 13 days (5 to 330 days). In-hospital or 30-day mortality was 3.6% (9). Overall survival at 3 years was 44%; median survival was 25 months, and 3-year survival by posttreatment pathologic stage was: stage 0 (complete response) (n = 60), 56%; stage I (n = 32), 65%; stage IIA (n = 67), 41%; stage IIB (n = 30), 46%; and stage III (n = 49), 17%. Mean follow-up was 24 months (SEM 1.6, 0 to 138 months). Five patients with tumor in situ, 6 patients with stage IV disease, and 1 patient who could not be staged (12 pts) were excluded from survival and multivariate calculations. In univariate and different models of multivariate analysis, age more than 65 years, posttreatment T3, and nodal involvement were predictive of poor survival. For univariate analysis, p = 0.002, p = 0.004, p = 0.02, respectively; for multivariate analysis, p = 0.001, p = 0.003, p = 0.02, respectively. CONCLUSIONS: Total thoracic esophagectomy with node dissection for esophageal cancer appears to have acceptable morbidity and mortality with encouraging survival results in the setting of neoadjuvant therapy. Patients who show complete response after induction chemoradiotherapy appear to have improved long-term survival.

The safety and versatility of video-thoracoscopy: a prospective analysis of 895 consecutive cases.

BACKGROUND: The application of video-endoscopy to general thoracic surgery is radically changing the approach to many benign and malignant diseases of the chest. Since July 1991, we have performed 794 purely thoracoscopic and 101 video-assisted thoracic surgical (VATS) procedures on 860 patients. STUDY DESIGN: Comprehensive, prospectively acquired data examining the specific indications for and outcomes of this new technique were prospectively entered into a thoracic surgical database. Preoperative, intraoperative, postoperative, and outcome variables were studied for the entire group as well as three high-risk cohorts: age over 70 years (n = 198), forced expiratory volume in one second (FEV1) of less than 1 L (n = 46), and Karnofsky performance index of less than 8 (n = 61). RESULTS: The 895 cases involved 449 men and 446 women of ages 15 to 89 years (mean 56 +/- 16 years standard deviation). The indications for surgery were diagnostic in 501 cases (56 percent), therapeutic in 244 cases (27 percent), and both diagnostic and therapeutic in an additional 150 cases (17 percent). The specific procedures performed were operations on the lung (569 cases), pleura (196 cases), esophagus (42 cases), mediastinum (51 cases), and pericardium (37 cases). Fifty-seven percent of the procedures were for a malignant process and 43 percent were for benign or infectious pathology. There were nine deaths for a series operative mortality rate of 1.0 percent. Thirteen patients (1.4 percent) required conversion to a limited thoracotomy for technical reasons. There were 127 complications in 121 patients yielding a morbidity rate in all patients of 14 percent. Mortality rates in the elderly, poor lung function, and depressed performance index cohorts were 1.5, 2.1, and 9.8 percent, respectively. Morbidity rates in these high-risk populations were 19, 30, and 18 percent, respectively. The median postoperative length of stay was three days after closed thoracoscopy and five days after VATS resection. CONCLUSIONS: These data underscore the flexibility, safety, efficacy, and potential for cost savings of videoscopic surgery in patients with thoracic diseases. The ability to perform excisional biopsy improves diagnostic specificity and sensitivity to nearly 100 percent. Video-assisted thoracic surgical techniques also offer a minimally invasive procedure with acceptable risk to patients heretofore inoperable by standard thoracotomy.