Paul C. Lee

Thoracoscopic lobectomy is associated with lower morbidity than open lobectomy: A propensity-matched analysis from the STS database

BACKGROUND Several single-institution series have demonstrated that compared with open thoracotomy, video-assisted thoracoscopic lobectomy may be associated with fewer postoperative complications. In the absence of randomized trials, we queried the Society of Thoracic Surgeons database to compare postoperative mortality and morbidity following open and video-assisted thoracoscopic lobectomy. A propensity-matched analysis using a large national database may enable a more comprehensive comparison of postoperative outcomes. METHODS All patients having lobectomy as the primary procedure via thoracoscopy or thoracotomy were identified in the Society of Thoracic Surgeons database from 2002 to 2007. After exclusions, 6323 patients were identified: 5042 having thoracotomy, 1281 having thoracoscopy. A propensity analysis was performed, incorporating preoperative variables, and the incidence of postoperative complications was compared. RESULTS Matching based on propensity scores produced 1281 patients in each group for analysis of postoperative outcomes. After video-assisted thoracoscopic lobectomy, 945 patients (73.8%) had no complications, compared with 847 patients (65.3%) who had lobectomy via thoracotomy (P < .0001). Compared with open lobectomy, video-assisted thoracoscopic lobectomy was associated with a lower incidence of arrhythmias [n = 93 (7.3%) vs 147 (11.5%); P = .0004], reintubation [n = 18 (1.4%) vs 40 (3.1%); P = .0046], and blood transfusion [n = 31 (2.4%) vs n = 60 (4.7%); P = .0028], as well as a shorter length of stay (4.0 vs 6.0 days; P < .0001) and chest tube duration (3.0 vs 4.0 days; P < .0001). There was no difference in operative mortality between the 2 groups. CONCLUSIONS Video-assisted thoracoscopic lobectomy is associated with a lower incidence of complications compared with lobectomy via thoracotomy. For appropriate candidates, video-assisted thoracoscopic lobectomy may be the preferred strategy for appropriately selected patients with lung cancer.

Total Number of Resected Lymph Nodes Predicts Survival in Esophageal Cancer

Objective:Several population-based studies have shown that the total number of surgically removed lymph nodes is independently associated with overall and disease-free survival in a variety of gastrointestinal cancers. In this retrospective study, the impact of total nodal count on overall survival in esophageal cancer was examined using a single institution surgical database. Methods:We conducted a retrospective review of 264 patients with esophageal cancer treated by esophagectomy without neoadjuvant therapy between January 1988 and December 2006. The association between overall survival (the primary endpoint) and the total number of dissected lymph nodes was evaluated using multivariable Cox regression models. Results:When the total number of resected nodes was examined as a categorical variable based on quartiles (category 1: ≤16, category 2: 17–25, category 3: 26–40, category 4: >40) there was a reduced hazard of death with increasing number of examined nodes. Compared with those in category 1, the death hazard was reduced by 34% (P = 0.08), 48% (P = 0.001), and 49% (P = 0.001), respectively, for patients in categories 2, 3, and 4. For node negative patients a significantly reduced hazard was present only when more than 40 nodes were resected (HR = 0.23, P = 0.01). For node positive patients the death hazard was significantly reduced for those in all higher categories compared with those in category 1 (HR = 0.53, 0.39, 0.49; P = 0.03, 0.001, 0.02, respectively). Conclusion:These data support the findings from population based studies in esophageal cancer and other gastrointestinal tumors, suggesting that a higher nodal count favorably influences survival.

Phase II Proof-of-Concept Study of Pazopanib Monotherapy in Treatment-Naive Patients With Stage I/II Resectable Non-Small-Cell Lung Cancer

PURPOSE Patients with early-stage, resectable, non-small-cell lung cancer (NSCLC) are at risk for recurrent disease, and 5-year survival rates do not exceed 75%. Angiogenesis inhibitors have shown clinical activity in patients with late-stage NSCLC, raising the possibility that targeting the vascular endothelial growth factor pathway in earlier-stage disease may be beneficial. This proof-of-concept study examined safety and efficacy of short-term, preoperative pazopanib monotherapy in patients with operable stage I/II NSCLC. PATIENTS AND METHODS Patients scheduled for resection received oral pazopanib 800 mg/d for 2 to 6 weeks preoperatively. Tumor response was measured by high-resolution computed tomography, permitting estimation of change in tumor volume and diameter. Gene-expression profiling was performed on 77 pre- and post-treatment lung samples from 34 patients. RESULTS Of 35 patients enrolled, 33 (94%) had clinical stage I NSCLC and two (6%) had clinical stage II NSCLC. Median treatment duration was 16 days (range, 3 to 29 days). Thirty patients (86%) achieved tumor-volume reduction after pazopanib treatment. Two patients achieved tumor-volume reduction > or = 50%, and three patients had partial response according to Response Evaluation Criteria in Solid Tumors. Pazopanib was generally well tolerated. The most common adverse events included grade 2 hypertension, diarrhea, and fatigue. One patient developed pulmonary embolism 11 days after surgery. Several pazopanib target genes and other angiogenic factors were dysregulated post-treatment. CONCLUSION Short-duration pazopanib was generally well tolerated and demonstrated single-agent activity in patients with early-stage NSCLC. Several target genes were dysregulated after pazopanib treatment, validating target-specific response and indicating a persistent pazopanib effect on lung cancer tissue. Further clinical evaluation of pazopanib in NSCLC is planned.

Outcomes after lobectomy using thoracoscopy vs thoracotomy: a comparative effectiveness analysis utilizing the Nationwide Inpatient Sample database

OBJECTIVES We examined the Nationwide Inpatient Sample (NIS) database to compare short-term postoperative outcomes following open and thoracoscopic lobectomy. Thoracoscopic (video-assisted thoracic surgery) lobectomy has been demonstrated to be associated with fewer postoperative complications compared with open thoracotomy lobectomy in several large case series. However, as no randomized trial has been performed, there are many who question this. METHODS We examined the NIS database for all patients undergoing lobectomy as their principal procedure either via thoracoscopic or open thoracotomy from 2007 to 08. We compared the postoperative outcomes of these two groups of patients after propensity matching these groups based on several preoperative variables. RESULTS Over a 2-year-period, 68 350 patients underwent a lobectomy by either thoracoscopy [n = 10 554 (15%)] or thoracotomy [n = 57 796(85%)]. Thirty-two percent of thoracoscopic lobectomies (n = 3421) were performed in either rural or non-teaching urban centres. Although in propensity-matched cohorts there was no difference in operative mortality, thoracoscopic lobectomy was associated with a lower incidence of postoperative complications [n = 4146 (40.8%) vs n = 13 913 (45.1%), P < 0.001] and shorter length of stay (5.0 vs 7.0 days; P < 0.001) compared with open lobectomy. Specifically, the incidences of supraventricular arrhythmias, myocardial infarction, pulmonary embolism and empyema were lower. CONCLUSIONS This large national database study demonstrates that thoracoscopic lobectomy is associated with fewer in-hospital postoperative complications compared with open lobectomy. Thoracoscopic lobectomy appears to be applicable to the wider general thoracic surgical community.

CXCL12 and CXCR4 in adenocarcinoma of the lung: Association with metastasis and survival

OBJECTIVES Although the chemokine CXCL12 and its receptor CXCR4 have been implicated in metastasis of non-small cell lung carcinoma, the prognostic significance of these molecules is poorly defined. This study aimed to determine whether expression of these molecules is associated with clinicopathologic features and disease-free survival in non-small cell lung carcinoma. METHODS Immunohistochemical staining for CXCL12 and CXCR4 was performed on 154 primary non-small cell lung carcinomas. Staining intensity was compared with tumor histotype, TNM stage, and disease-free survival; correlation was assessed by using the Fishers exact test, and Kaplan-Meier and Cox multivariate proportional hazards regression analysis. RESULTS Intense CXCL12 immunostaining was associated with nodal metastasis, although no difference in survival was observed. The prognostic relevance of CXCR4 was dependent on its subcellular location: in univariate analysis intense nuclear staining was significantly associated with lower T classification and improved disease-free survival in patients with adenocarcinoma, whereas cytomembranous staining was associated with distant metastasis and decreased disease-free survival. On multivariate analysis, cytomembranous CXCR4 expression conferred a significantly worse disease-free survival (relative risk, 2.8; 95% confidence interval, 1.4-5.7; P = .004). CONCLUSIONS Cytomembranous expression of the chemokine receptor CXCR4 in adenocarcinoma of the lung is an independent risk factor associated with worse disease-free survival, whereas nuclear staining confers a survival benefit. These findings are consistent with a model in which CXCR4 promotes tumor cell proliferation and metastasis when present in the cytoplasm or cell membrane, whereas localization of this molecule in the nucleus prevents it from exerting these effects.

Lobectomy in Octogenarians With Non-Small Cell Lung Cancer: Ramifications of Increasing Life Expectancy and the Benefits of Minimally Invasive Surgery

BACKGROUND As the population ages, clinicians are increasingly confronted with octogenarians with resectable non-small cell lung cancer (NSCLC). We reviewed the outcomes of octogenarians who underwent lobectomy for NSCLC by video-assisted thoracic surgery (VATS) versus open thoracotomy, to determine if there was a benefit to the VATS approach in this group. METHODS We conducted a retrospective single-institution review of patients age 80 years or greater who underwent a lobectomy for NSCLC from 1998 to 2009. Outcomes including complication rates, length of stay, disposition, and long-term survival were analyzed. RESULTS One hundred twenty-one octogenarians underwent lobectomy: 40 VATS and 81 through open thoracotomy. Compared with thoracotomy, VATS patients had fewer complications (35.0% vs 63.0%, p = 0.004), shorter length of stay (5 vs 6 days, p = 0.001), and were less likely to require admission to the intensive care unit (2.5% vs 14.8%, p = 0.038) or rehabilitation after discharge (5% vs 22.5%, p = 0.015). In multivariate analysis, VATS was an independent predictor of reduced complications (odds ratio, 0.35; 95% confidence interval, 0.15 to 0.84; p = 0.019). Survival comparisons demonstrated no significant difference between the two techniques, either in univariate analysis of stage I patients (5-year VATS, 76.0%; thoracotomy, 65.3%; p = 0.111) or multivariate analysis of the entire cohort (adjusted hazard ratio, 0.59; 95% confidence interval, 0.27 to 1.28; p = 0.183). CONCLUSIONS Octogenarians with NSCLC can undergo resection with low mortality and survival among stage I patients, which is comparable with the general lung cancer population. The VATS approach to resection reduces morbidity in this age demographic, resulting in shorter, less intensive hospitalization, and less frequent need for postoperative rehabilitation.

Multifocal neoplasia and nodal metastases in T1 esophageal carcinoma: implications for endoscopic treatment.

Objective:There has been an increase in interest in endoscopic therapy (ET) for intramucosal (T1a) or submucosal (T1b) esophageal carcinoma. The objective of the present study was to determine the prevalence of nodal metastases, lymphatic vascular invasion, and multifocal neoplasia in patients with pT1 esophageal carcinoma who underwent esophagectomy without preoperative therapy and assess their potential implication for ET. Methods:We retrospectively reviewed the records of all patients who underwent esophagectomy without preoperative therapy for pT1 esophageal cancer. A detailed review of all pathology reports was performed to identify relevant pathologic criteria including depth of invasion (T1a or T1b), cell type (adenocarcinoma/squamous), tumor differentiation (poor vs. well/moderate), extent of Barrett esophagus (short segment [SSBE] and long segment [LSBE]), nodal status, lymphovascular invasion (LVI), and the presence of multifocal neoplasia (MFN) (high-grade dysplasia or invasive carcinoma). Overall survival and disease-specific survival were determined by the Kaplan-Meier method. Results:There were 75 consecutive patients (58 men, 17 women) between January 1994 and September 2006. Median age was 68 years. Hospital mortality was 2.6% (2 of 75). Thirty patients had T1a and 45 had T1b. Sixty patients had adenocarcinoma. Nodal metastases were present in 2 of 30 (6%) T1a and 8 of 45 (17.5%) T1b tumors. MFN was present in 30% (9 of 30) of T1a tumors and 29% (13 of 45) of T1b tumors. All 9 patients with LVI had T1b tumors. Collectively, 10 of 30 (33.3%) patients with T1a and 25 of 45 (58%) with T1b had MFN, LVI, or nodal metastases. Forty-nine patients had adenocarcinoma with associated BE (23 SSBE, 26 LSBE). There was no difference between patients with SSBE and those with LSBE in the incidence of nodal disease (2 of 23 vs. 2 of 26) but a significant difference in the incidence of MFN (3 of 23 vs. 13 of 26, P = 0.006). Four patients with squamous carcinoma had nodal metastases and 5 had MFN. Overall 5-year survival was 78% (T1a:90% T1b: 71%, P = 0.07). Five-year disease-specific survival was 86.5% (T1a: 96.7%, T1b: 79.6%, P = 0.06). Conclusion:The combined high incidence of MFN, LVI, and occult nodal metastases does not support the use of ET in patients with T1 esophageal cancer regardless of depth of invasion, cell type, differentiation or extent of BE. ET may be of value in patients in whom surgical risk is considered prohibitive.

Clinical T2-T3N0M0 Esophageal Cancer: The Risk of Node Positive Disease

BACKGROUND No consensus exists on the optimal treatment strategy for clinical T2-T3N0M0 esophageal cancer. This study was conducted to determine rates of nodal positivity (N+) and to evaluate results of treatment strategies in this cohort. METHODS Surgically treated patients with cT2-T3N0M0 esophageal cancer were reviewed. Adequacy of lymph node dissection was assessed by guidelines applied to clinical stage. Survival was determined by Kaplan-Meier analysis. Univariate and multivariate analyses were done for predictors of N+ and survival. RESULTS We identified 102 patients, 51 cT2N0 and 51 cT3N0, 39 (38%) of whom had induction therapy. Despite being clinically node negative, 61 patients (60%) had nodal metastases. Applied to cT classification, adequate nodal dissection was achieved in 64 patients (63%). Transthoracic esophagectomy was more likely than transhiatal esophagectomy to achieve adequate nodal dissection (69% versus 31%, p=0.005). Adequate nodal dissection was more likely to document pN+ disease in both the surgery alone group (70% versus 50%, p=0.13) and induction therapy group (71% versus 33%, p=0.02). Five-year overall survival was 44% with surgery alone and 55% with induction therapy. On multivariate analysis, pN+ was the strongest predictor of overall survival (relative risk 2.73, confidence interval: 1.29 to 5.78). CONCLUSIONS Most cT2-T3N0M0 patients have pN+ disease. Despite induction therapy, more than 50% have persistent nodal disease. Transthoracic esophagectomy is more likely to detect pN+ disease and more likely to meet criteria of adequate nodal dissection than is transhiatal esophagectomy. Therefore, the majority of patients with cT2-T3N0M0 should be considered for neoadjuvant protocols and should be treated by transthoracic resection whenever possible.

Long-Term Survival After Lobectomy for Non-Small Cell Lung Cancer by Video-Assisted Thoracic Surgery Versus Thoracotomy

BACKGROUND Video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) is increasingly popular. However, the oncologic soundness of VATS for patients with NSCLC as measured by long-term survival has not been proven. The objective here is to determine the overall survival (OS) and disease-free survival (DFS) in two well-matched groups of patients with NSCLC resected by VATS or thoracotomy. METHODS We conducted a retrospective review of a prospective database to identify patients who had a lobectomy for NSCLC. A propensity score-matched analysis was done with variables of age, sex, smoking history, Charlson comorbidity index, forced expiratory volume in 1 second, lung diffusing capacity for carbon monoxide, histology, and clinical T and N status. Medical records were reviewed and survival was analyzed. RESULTS After matching, there were 208 patients in each group. Patient and tumor characteristics were similar. The VATS group had a shorter length of stay. More nodes (14.3 versus 11.3; p=0.001) and more nodal stations (3.8 versus 3.1; p<0.001) were removed by thoracotomy. No differences were seen in OS and DFS. Median follow-up was 36 months. More than 90% of patients had clinical stage I disease, with 3- and 5-year OS of 87.4% and 76.5%, respectively, for VATS, and 81.6% and 77.5%, respectively, for thoracotomy (p=0.672). Both the incidence and distribution of recurrence were similar. Multivariate Cox regression analyses of OS and DFS confirmed the noninferiority of VATS. CONCLUSIONS For patients with clinical stage I NSCLC, VATS lobectomy offered similar OS and DFS compared with thoracotomy. Thoracotomy offers a more thorough lymph node evaluation, and may be appropriate for patients with more advanced clinical disease.

Surgical management of chylothorax.

BACKGROUND Chylothorax remains an uncommon but challenging clinical problem. Thoracic duct ligation is the treatment of choice for postsurgical patients. However, the optimal treatment for traumatic patients is unclear. We wanted to examine the outcomes of patients with high output or recurrent chylothorax who were treated by surgical means. METHODS From December 1992 to April 2008, 29 patients underwent surgical procedures for high output (> 1 L/day) (16) or recurrent chylothorax (13). We analyzed these patients to determine the surgical approach, perioperative complications, and outcomes of the treatment approach. RESULTS Of the 29 patients, 12 patients developed chylothorax following esophagectomy, in 5 patients it resulted from lymphoproliferative disorders, in 2 patients following ascending aneurysm repair, in 2 after trauma, in 3 following lung resection, and in 1 patient respectively from coronary artery bypass grafting (CABG), thymectomy for thymoma, vasculitis, and metastatic lung cancer, while 1 patient had no clear etiology. The median age of patients was 61 (range 20-79) years. 22 patients initially underwent thoracic duct ligation, 6 had talc pleurodesis, and one underwent bilateral pleuroperitoneal shunt placement. Approaches for thoracic duct ligation included: right thoracotomy (16), left thoracotomy (3), VATS (2), and right thoracotomy together with laparotomy (1). There were no intraoperative complications or deaths within 30 days or during postoperative hospitalization. The success rate after initial thoracic duct ligation was 95 % (21/22). One patient needed re-exploration after ligation with resolution of chylothorax after the second operation. The success rate after pleurodesis was 83 % (5/6). One patient after pleurodesis needed subsequent thoracic duct ligation for resolution of bilateral chylothoraces. All patients in this series had resolution of chylothorax. CONCLUSIONS Thoracic duct ligation is the treatment of choice for high output or recurrent chylothorax with a 96 % success rate. Surgical pleurodesis is effective in some cases and may be an option for marginal patients.