Cameron D. Wright

POSTINTUBATION TRACHEAL STENOSIS. TREATMENT AND RESULTS

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

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.

Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer.

PURPOSE The main objectives of this study were (a) to ascertain the feasibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in stage IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate tumor response, resection rate, pathologic tumor downstaging, and survival. METHODS Eligibility included biopsy-proven N2 lesion (stage IIIA) by mediastinoscopy, Karnofsky performance score > or = 70, and weight loss less than 5% in the 3 months before diagnosis. The treatment program consisted of two courses of preoperative cisplatin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; and one more course of postoperative chemotherapy and 12 to 18 Gy of concurrent twice-daily radiation. RESULTS Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enrolled onto this prospective study. Forty of 42 patients tolerated the intended dose (42 Gy) of preoperative radiation and 37 of 39 resected patients received prescribed postoperative radiation. The intended dose of chemotherapy was given in 100%, 70%, and 60% of patients for the first, second, and third courses of chemotherapy. Marked dysphagia that required intravenous hydration was noted in 14% of patients (six of 42). Myelotoxicities included grade > or = 3 granulocytopenia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% of 113 chemotherapy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. The overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2,3, and 5 years, respectively, with a median follow-up time of 48 months. Pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (NO) in 24% (10 of 42), and to stage 0 (TONO) in 9.5%, for a total of 67%. The degree of tumor downstaging was also translated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04). CONCLUSION Concurrent chemoradiotherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful intermediate end point for survival benefit in stage IIIA (N2) NSCLC.

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.

Vaccination With Irradiated Autologous Tumor Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor Augments Antitumor Immunity in Some Patients With Metastatic Non–Small-Cell Lung Carcinoma

PURPOSE We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial. PATIENTS AND METHODS Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals. RESULTS Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed. CONCLUSION Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.

Thymoma: State of the Art

Thymoma is the most common tumor of the anterior mediastinum. This tumor is associated with unique paraneoplastic syndromes, such as myasthenia gravis, hypogammaglobulinemia, and pure red cell aplasia. The rarity of this tumor, however, has somewhat obscured the optimal treatment for this disease. For the majority of patients who present with localized tumor, surgical extirpation remains the standard of choice. Adjuvant radiotherapy seems to improve local control and survival. In more advanced disease, systemic therapy has been demonstrated to produce a 50% to 80% objective response rate. These observations have led to the development of multimodality therapy for the treatment of patients with advanced thymoma. In this article, we will review the current perspectives on the management of early stage and advanced thymoma.

Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: A Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model

OBJECTIVE To create a model for perioperative risk of esophagectomy for cancer using the Society of Thoracic Surgeons General Thoracic Database. METHODS The Society of Thoracic Surgeons General Thoracic Database was queried for all patients treated with esophagectomy for esophageal cancer between January 2002 and December 2007. A multivariable risk model for mortality and major morbidity was constructed. RESULTS There were 2315 esophagectomies performed by 73 participating centers. Hospital mortality was 63/2315 (2.7%). Major morbidity (defined as reoperation for bleeding [n = 12], anastomotic leak [n = 261], pneumonia [n = 188], reintubation [n = 227], ventilation beyond 48 hours [n = 71], or death [n = 63]) occurred in 553 patients (24%). Preoperative spirometry was obtained in 923/2315 (40%) of patients. A forced expiratory volume in 1 second < 60% of predicted was associated with major morbidity (P = .0044). Important predictors of major morbidity are: age 75 versus 55 (P = .005), black race (P = .08), congestive heart failure (P = .015), coronary artery disease (P = .017), peripheral vascular disease (P = .009), hypertension (P = .029), insulin-dependent diabetes (P = .009), American Society of Anesthesiology rating (P = .001), smoking status (P = .022), and steroid use (P = .026). A strong volume performance relationship was not observed for the composite measure of morbidity and mortality in this patient cohort. CONCLUSIONS Thoracic surgeons participating in the Society of Thoracic Surgeons General Thoracic Database perform esophagectomy with a low mortality. We identified important predictors of major morbidity and mortality after esophagectomy for esophageal cancer. Volume alone is an inadequate proxy for quality assessment after esophagectomy.

STS Database Risk Models: Predictors of Mortality and Major Morbidity for Lung Cancer Resection

BACKGROUND The aim of this study is to create models for perioperative risk of lung cancer resection using the STS GTDB (Society of Thoracic Surgeons General Thoracic Database). METHODS The STS GTDB was queried for all patients treated with resection for primary lung cancer between January 1, 2002 and June 30, 2008. Three separate multivariable risk models were constructed (mortality, major morbidity, and composite mortality or major morbidity). RESULTS There were 18,800 lung cancer resections performed at 111 participating centers. Perioperative mortality was 413 of 18,800 (2.2%). Composite major morbidity or mortality occurred in 1,612 patients (8.6%). Predictors of mortality include the following: pneumonectomy (p < 0.001), bilobectomy (p < 0.001), American Society of Anesthesiology rating (p < 0.018), Zubrod performance status (p < 0.001), renal dysfunction (p = 0.001), induction chemoradiation therapy (p = 0.01), steroids (p = 0.002), age (p < 0.001), urgent procedures (p = 0.015), male gender (p = 0.013), forced expiratory volume in one second (p < 0.001), and body mass index (p = 0.015). CONCLUSIONS Thoracic surgeons participating in the STS GTDB perform lung cancer resections with a low mortality and morbidity. The risk-adjustment models created have excellent performance characteristics and identify important predictors of mortality and major morbidity for lung cancer resections. These models may be used to inform clinical decisions and to compare risk-adjusted outcomes for quality improvement purposes.

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

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

Reinforced primary repair of thoracic esophageal perforation

BACKGROUND Treatment of esophageal perforation, especially when diagnosed late, remains controversial. METHODS Twenty-eight patients were treated for thoracic esophageal perforation with reinforced primary repair regardless of time of presentation. RESULTS Fifteen patients were treated early (< 24 hours) with no deaths. Two had contained postoperative leaks, which healed. Thirteen were treated late (mean, 5.5 days) with four deaths (3 with healed repairs). Postoperative leaks occurred in 7 patients; of the leaks, 4 healed, 2 became a controlled fistula, and 1 required reoperation. Primary healing with preservation of the native esophagus was achieved in 25 patients (89%). Among the 18 patients without evidence of sepsis preoperatively, post-operative leaks developed in 2 (11%). Ten patients had evidence of sepsis preoperatively, and postoperative leaks developed in 7 (70%). CONCLUSIONS Patients who present with sepsis have an increased risk of postoperative leak and therefore should have the repair buttressed. Overall mortality was 14% and no deaths were due to persistent leaks or mediastinal sepsis. Reinforced primary repair retains the native esophagus and avoids the need for later reconstructive operations. In the absence of a nondilatable stricture or cancer, reinforced primary repair should be performed for most thoracic esophageal perforations, early or late.