Henning A. Gaissert

Data from The Society of Thoracic Surgeons General Thoracic Surgery database: the surgical management of primary lung tumors.

OBJECTIVE Our objective was to investigate the surgical management of primary lung cancer by board-certified thoracic surgeons participating in the general thoracic surgery portion of The Society of Thoracic Surgeons database. METHODS We identified all pulmonary resections recorded in the general thoracic surgery prospective database from 1999 to 2006. Among the 49,029 recorded operations, 9033 pulmonary resections for primary lung cancer were analyzed. RESULTS There were 4539 men and 4494 women with a median age of 67 years (range 20-94 years). Comorbidity affected 79% of patients and included hypertension in 66%, coronary artery disease in 26%, body mass index of 30 kg/m2 or more in 25.7%, and diabetes mellitus in 13%. The type of resection was a wedge resection in 1649 (18.1%), segmentectomy in 394 (4.4%), lobectomy in 6042 (67%), bilobectomy in 357 (4.0%), and pneumonectomy in 591 (6.5%). Mediastinal lymph nodes were evaluated in 5879 (65%) patients; via mediastinoscopy in 1928 (21%), nodal dissection 3722 (41%), nodal sampling in 1124 (12.4%), and nodal biopsy in 729 (8%). Median length of stay was 5 days (range 0-277 days). Operative mortality was 2.5% (179 patients). One or more postoperative events occurred in 2911 (32%) patients. CONCLUSION The patients in the general thoracic surgery database are elderly, gender balanced, and afflicted by multiple comorbid conditions. Mediastinal lymph node evaluation is common and the pneumonectomy rate is low. The length of stay is short and operative mortality is low, despite frequent postoperative events.

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

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

Comparison of early functional results after volume reduction or lung transplantation for chronic obstructive pulmonary disease

BACKGROUND Bilateral lung volume reduction is designed to improve pulmonary function in selected patients with severe emphysema by improving diaphragmatic and chest wall mechanics. Early results of lung volume reduction suggest significant improvement to selected patients with chronic obstructive pulmonary disease, some of whom might otherwise be considered for lung transplantation. The purpose of this review was to compare intermediate results of volume reduction with single and bilateral lung transplantation. METHODS Functional performance and survival after volume reduction were compared with single and bilateral sequential lung transplantation. After evaluation, patients were enrolled in a supervised intensive preoperative and postoperative program of pulmonary rehabilitation. Functional assessment, including pulmonary function tests, room air arterial blood gas analysis, and 6-minute walk distance, was obtained before the operation and 3, 6, and 12 months after the operation. RESULTS Thirty-three patients underwent volume reduction (mean age 57 years), 39 patients single lung transplantation (55 years), and 27 patients bilateral lung transplantation (49 years). Early mortality was 0, 1 of 39, and 2 of 25 and mortality at 12 months was 1 of 33, 4 of 39, and 4 of 25 in the volume reduction, single, and bilateral lung transplantation groups, respectively. At 6 months, mean forced expiratory volume in 1 second was improved by 79% (volume reduction), by 231% (single lung transplantation), and by 498% (bilateral lung transplantation) over preoperative values. Exercise endurance as measured by 6-minute walk distance increased by 28% (volume reduction), by 47% (single lung transplantation), and by 79% (bilateral lung transplantation) from baseline. At 6 months, all patients having single or bilateral lung transplantation and 26 of 33 patients having volume replacement were free of supplemental oxygen. CONCLUSIONS Although single and bilateral lung transplantation result in superior lung function, volume reduction achieves satisfactory improvement of disabling symptoms early after operation while avoiding immunosuppression and transplant-specific complications. Our experience suggests that (1) volume reduction is a suitable alternative in selected patients eligible for transplantation; (2) volume reduction provides an earlier option for treatment in patients who may require transplantation at some future date; (3) volume reduction is the only surgical treatment available to the many patients who are not current or future transplant candidates. Conversely, in patients not suitable for volume reduction, transplantation remains the only choice for surgical therapy.

Predictors of prolonged length of stay after lobectomy for lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk-adjustment model.

BACKGROUND Few reliable estimations of operative risk exist for lung cancer patients undergoing lobectomy. This study identified risk factors associated with prolonged length of hospital stay (PLOS) after lobectomy for lung cancer as a surrogate for perioperative morbid events. METHODS The Society of Thoracic Surgeons (STS) General Thoracic Surgery Database was queried for patients with lobectomy for lung cancer. A model of preoperative risk factors was developed by multivariate stepwise logistic regression setting the threshold for PLOS at 14 days. Morbidity was measured as postoperative events as defined in the STS database. Risk-adjusted results were reported to participating sites. RESULTS From January 2002 to June 2006, 4979 lobectomies were performed for lung cancer at 56 STS sites, and 351 (7%) had a PLOS. They had more postoperative events than patients without PLOS (3.4 vs 1.2; p < 0.0001). Patients with PLOS also had higher mortality than those with normal LOS, at 10.8% (38 of 351) vs 0.7% (33 of 4628; p < 0.0001). Significant predictors of PLOS included age per 10 years (odds ratio [OR], 1.30, p < 0.001), Zubrod score (OR, 1.51; p < 0.001), male sex (OR, 1.45; p = 0.002), American Society of Anesthesiology score (OR, 1.54; p < 0.001), insulin-dependent diabetes (OR. 1.71; p = 0.037), renal dysfunction (OR, 1.79; p = 0.004), induction therapy (OR, 1.65; p = 0.001), percentage predicted forced expiratory volume in 1 second in 10% increments (OR, 0.88; p < 0.001), and smoking (OR, 1.33; p = 0.095). After risk adjustment, twofold interhospital variability existed in PLOS among STS sites CONCLUSIONS We identified significant predictors of PLOS, a surrogate morbidity marker after lobectomy for lung cancer. This model may be used to provide meaningful risk-adjusted outcome comparisons to STS sites for quality improvement purposes.

Complication of benign tracheobronchial strictures by self-expanding metal stents

OBJECTIVES Self-expanding metal stents are used to palliate benign strictures. We examined the complications of this approach. METHODS Between 1997 and 2002, we observed recurrent airway obstruction and extension of benign inflammatory strictures after the placement of tracheobronchial Microvasive Ultraflex stents and Wallstents (Boston Scientific Corp, Natick, Mass), in 10 patients with postintubation strictures and 5 with other indications; all but 1 patient were referred to us. Patients with tracheal (9), subglottic (1), combined tracheal and subglottic (3), and bronchial (2) strictures had been treated with covered and uncovered Wallstents (6) and Microvasive Ultraflex stents (9). RESULTS After stent insertion, stricture and granulations within previously normal airway were seen in all patients. New subglottic strictures resulting from the stent caused hoarseness in 4 patients. A bronchoesophageal fistula was found in 1 patient at presentation and a tracheoesophageal fistula in another during extraction of a Wallstent. Primary surgical reconstruction, judged to have been feasible before wire stent insertion in 10 patients, was possible after stenting in only 7 and failed in 2. Palliative tubes were placed in 60% (9/15). Self-expanding metal stents may lengthen luminal damage, incite subglottic strictures, and cause esophagorespiratory fistula in inflammatory airway strictures. The injury is severe, occurs after a short duration of stenting, and precludes definitive surgical treatment or requires more extensive tracheal resection. CONCLUSION The current generation of self-expanding metal stents should be avoided in benign strictures of trachea and bronchi.

Survival and function after sleeve lobectomy for lung cancer

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

Tissue-engineered esophagus: experimental substitution by onlay patch or interposition

OBJECTIVES We proposed to fabricate a tissue-engineered esophagus and to use it for replacement of the abdominal esophagus. METHODS Esophagus organoid units, mesenchymal cores surrounded by epithelial cells, were isolated from neonatal or adult rats and paratopically transplanted on biodegradable polymer tubes, which were implanted in syngeneic hosts. Four weeks later, the tissue-engineered esophagus was either harvested or anastomosed as an onlay patch or total interposition graft. Green Fluorescent Protein labeling by means of viral infection of the organoid units was performed before implantation. Histology and immunohistochemical detection of the antigen alpha-actin smooth muscle were performed. RESULTS Tissue-engineered esophagus grows in sufficient quantity for interposition grafting. Histology reveals a complete esophageal wall, including mucosa, submucosa, and muscularis propria, which was confirmed by means of immunohistochemical staining for alpha-actin smooth muscle. Tissue-engineered esophagus architecture was maintained after interposition or use as a patch, and animals gained weight on a normal diet. Green Fluorescent Protein-labeled tissue-engineered esophagus preserved its fluorescent label, proving the donor origin of the tissue-engineered esophagus. CONCLUSIONS Tissue-engineered esophagus resembles the native esophagus and maintains normal histology in anastomosis, with implications for therapy of long-segment esophageal tissue loss caused by congenital absence, surgical excision, or trauma.

Tracheobronchial gland tumors

BACKGROUND Tracheal tumors are uncommon, making up only 0.2% of all respiratory malignancies in the United States. One consequence of this low incidence is that few centers accumulate meaningful experience. Another is the lack of awareness of effective therapy. Bronchial gland tumors demonstrate oncologic diversity and include benign, low-grade, and high-grade malignant tumors. METHODS We reviewed the present knowledge of bronchial gland tumors of the trachea, carina, and bronchi, including the epidemiology, presentation, evaluation, tumor types, and treatment options. RESULTS The malignant bronchial gland tumors, adenoid cystic carcinoma and mucoepidermoid carcinoma, are far more common than benign mucinous cystadenoma or pleomorphic adenoma. Complete resection of localized tumors has excellent long-term results in symptomatic benign tumors. The disease-free survival after resection of malignant tumors is limited by distant metastasis and regional disease, while local recurrence is uncommon. Postoperative mediastinal radiation is now accepted adjuvant therapy. Experience at our institute demonstrates a significant survival advantage for patients with complete resection compared to unresectable patients. CONCLUSIONS Expanding knowledge of diagnostic evaluation and surgical therapy can improve the long-term survival of patients with tracheobronchial gland tumors.

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

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

Pulmonary Resection of Metastatic Sarcoma: Prognostic Factors Associated With Improved Outcomes

BACKGROUND There are few data to predict the benefit of pulmonary metastasectomy in patients with extrathoracic sarcoma. This study analyzes prognostic factors associated with improved outcomes. METHODS Between June 2002 and December 2008, 97 patients underwent pulmonary resection for metastatic sarcoma at Massachusetts General Hospital. Eight patients were excluded because of lack of follow-up data. Analysis was performed using Kaplan-Meier estimates of survival, log-rank test, and multivariate Cox model. RESULTS Overall 5-year survival for the cohort was 50.1%. Patients who had multiple operations for recurrent pulmonary metastases had better 5-year survival compared with patients who had a single operation (69 versus 41%; p = 0.017). Median disease- free survival (DFS) for the reoperation group was 12.9 months compared with 9.1 months for the single-operation group (p < 0.028). Patients with a disease-free interval (DFI) greater than 12 months from detection of primary sarcoma to pulmonary metastasectomy had improved survival compared with those whose DFI was less than 12 months (p < 0.0001). Patients with bilateral metastasectomy had lower 5-year survival compared with metastasectomy for unilateral disease (22% versus 68% ;p < 0.0001). Two or more metastases were associated with poorer outcome compared with a single metastasis (p = 0.0007). A positive resection margin portended worse survival compared with a negative resection margin (p = 0.004). Patients with lesions larger than 3 cm had decreased survival compared with patients with lesions smaller than 3 cm (p = 0.017) with no difference in median DFS. Histologic type, grade of tumor, and use of chemotherapy had no effect on survival. Multivariate analysis showed that patients with a DFI greater than 12 months (p = 0.001), single-sided metastasis (p = 0.001), negative margins (p = 0.002), and multiple operations (p = 0.018) had better survival. CONCLUSIONS Pulmonary metastasectomy for sarcoma can be associated with prolonged survival. Tumor resectability, DFI, number of metastases, and laterality are important factors in determining patient selection for curative surgical intervention. Repeated pulmonary metastasectomy in select patients may improve survival despite recurrent disease.