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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., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The goal of this study was to analyze factors predictive of recurrence and disease-free survival in patients with completely resected esophageal carcinoma., Methods: We conducted a retrospective review of a prospective database to identify patients with completely resected esophageal carcinoma. Medical records were reviewed. Recurrence rates, time to recurrence, and disease-free survival were analyzed. The Kaplan-Meier method was used for time to event estimation, and multivariate Cox regression models were constructed to analyze factors thought to be significant in determining both freedom from recurrence and disease-free survival., Results: From 1988 to 2009, 465 of 500 patients underwent complete resection for esophageal carcinoma. Median follow-up for living patients was 49 months; 197 patients (42.4%) had recurrence, leading to 175 patients dying of cancer and 22 patients living with recurrent disease. Multivariate regression adjusted for P stage identified the following variables as independent predictors of freedom from recurrence: performance status greater than 0 (hazard ratio [HR], 1.84; 95 confidence interval [CI], 1.35-2.49]; P < .001), poor differentiation (HR, 1.50; CI, 1.12-2.01; P = .006), induction therapy (HR, 1.65; CI, 1.21-2.25]; P = .002), en bloc resection (HR, 0.61; CI, 0.43-0.88; P = .007), and advanced pathologic stages (II/III/IV) (HR, 5.46; CI, 3.05-9.78; P < .001). Independent predictors of disease-free survival adjusted for P stage were performance status greater than 0 (HR, 1.73; CI, 1.34-2.23; P < .001), en bloc resection (HR, 0.63; CI, 0.47-0.84; P = .002), induction therapy (HR, 1.34; CI, 1.02-1.76; P = .033), and advanced pathologic stages (II/III/IV) (HR, 3.16; CI, 2.15-4.65; P < .001)., Conclusions: For patients with completely resected esophageal cancer, independent predictors of improved freedom from recurrence and disease-free survival include good performance status, en bloc resection, and early pathologic stage., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: In clinical stage IIIA non-small cell lung cancer, the role of surgical resection, particularly pneumonectomy, after induction therapy remains controversial. Our objective was to determine factors predictive of survival after postinduction surgical resection., Methods: We retrospectively reviewed a prospectively collected database of 136 patients who underwent surgical resection after induction chemotherapy (n = 119) or chemoradiation (n = 17) from June 1990 to January 2010., Results: One hundred five lobectomies or bilobectomies and 31 pneumonectomies were performed. There was 1 perioperative death (pneumonectomy). Seventy-one patients had downstaging to N0 or N1 nodal status (52%). There were 2 complete pathologic responses. Median follow-up was 42 months (range, 0.69-136 months). Overall 5-year survival for entire cohort was 33% (36% lobectomy, 22% pneumonectomy, P = .001). Patients with pathologic downstaging to pN0 or pN1 had improved 5-year survival (45% vs 20%, P = .003). For patients with pN0 or pN1 disease, survival after lobectomy was better than after pneumonectomy (48% vs 27%, P = .011). In patients with residual N2 disease, there was no statistically significant survival difference between lobectomy and pneumonectomy (5-year survival, 21% vs 19%; P = .136). Multivariate analysis showed as independent predictors of survival age (hazard ratio, 1.05; P = .002), extent of resection (hazard ratio, 2.01; P = .026), and presence of residual pN2 (hazard ratio, 1.60; P = .047)., Conclusions: After induction therapy for patients with clinical stage IIIA disease, both pneumonectomy and lobectomy can be safely performed. Although survival after lobectomy is better, long-term survival can be accomplished after pneumonectomy for appropriately selected patients. Nodal downstaging is important determinant of survival, particularly after lobectomy., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Although patients with esophageal cancer (EC) often develop lymph node metastases in the cervical and recurrent laryngeal (CRL) distribution, lymphadenectomy in this field is rarely performed. The purpose of this study was to determine factors associated with CRL node positivity and to determine the appropriate indications to perform a "three field" lymphadenectomy., Methods: In a retrospective review, EC patients who underwent three-field lymphadenectomy were analyzed. Predictors of positive CRL nodes were examined univariately, then selected for inclusion in a multivariate logistic regression model., Results: From 1994 to 2009, 185 patients had a three-field lymphadenectomy, of whom 46 patients (24.9%) had positive CRL nodes. Final pathology stages (seventh edition) were I in 24 patients, II in 43, III in 109, and IV in 1 patient. Eight patients had a major pathologic response after induction therapy. On univariate analysis, variables significantly associated with positive CRL nodes included squamous cell histology, proximal location, advanced clinical presentation, the presence of clinical nodal disease, higher pT classification, and higher pN classification. There was no reduction in the rate of positive CRL nodes after induction chemotherapy. On multivariate analysis, higher pN classification (adjusted odds ratio 16.25, 95% confidence interval: 5.40 to 48.87; p < 0.0001) and squamous histology (adjusted odds ratio 6.04, 95% confidence interval: 2.21 to 16.56; p < 0.0001) predicted positive CRL nodes., Conclusions: Complete lymphadenectomy is necessary in esophageal cancer to appropriately stage patients. Low rates of positive CRL nodes are present with early clinical stage, with pT0-2 tumors, and with pN0 classification, particularly in patients with adenocarcinoma and gastroesophageal junction tumors. Dissection of the CRL field should be considered with advanced disease for adenocarcinoma and in all patients with squamous cell cancer., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: In patients with esophageal cancer, a complete pathologic response after preoperative therapy is universally regarded as a favorable prognostic factor. However, less is known about factors predictive of outcome in patients with persistent nodal disease. The purpose of this study is to determine which variables affect survival in this patient population., Methods: We reviewed a prospectively maintained esophageal cancer database. Patients with positive lymph nodes after preoperative therapy and surgery were selected. Predictors of survival were examined univariately using the log-rank test. Factors identified at P < .20 by univariate analysis were selected for inclusion in a multivariate model., Results: Ninety-six patients with 1 or more positive nodes received preoperative therapy. Pathologic T classification was 0 to 2 in 25 (26%) patients and 3 to 4 in 71 (74%) patients. In 29 (30%) patients, nonregional nodal disease was present (M1). Final pathologic stages were IIB in 18 (19%), III in 49 (51%), and IV in 29 (30%). Postoperatively, 44 (46%) patients received additional chemotherapy. On univariate analysis, pathologic stage, pathologic T classification, and number of positive nodes significantly affected overall survival. On multivariate analysis, clinical stage (hazard ratio [HR], 2.25; P = .05), pathologic T classification (HR, 3.06; P = .006), and number of positive nodes (HR 1.03 per node, P = .09) were significant predictors of overall survival., Conclusion: Long-term survival can be achieved in patients with esophageal cancer who have persistent nodal disease after neoadjuvant therapy and surgical resection. Clinical stage, pathologic T classification, and number of positive nodes best predict survival. Nonregional nodal disease does not adversely affect outcome. Postoperative chemotherapy conferred no additional survival benefit in this patient population., (2010. Published by Mosby, Inc.)

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., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Patients with esophageal carcinoma and celiac, cervical, or other nonregional nodal metastases generally have a poor prognosis after surgical resection. Factors predicting long-term survival are unclear. The goal of this study was to analyze factors predicting long-term survival in this subset of patients., Methods: We conducted a retrospective review of a prospective database over a 20-year period to identify patients with resected esophageal carcinoma with nonregional lymph node metastases. Medical records were reviewed and risk factors were analyzed., Results: Sixty-seven patients underwent esophagectomy for M1a or M1b disease from 1987 to 2007. Esophagectomy was transthoracic in 62 patients and transhiatal in 5. The median number of lymph nodes harvested was 36. Sites of nodal metastases were the following: recurrent nodal chain in 42 patients, celiac in 20, both recurrent and celiac in 4, and paratracheal in 1. Median length of follow-up was 66 months. The 5-year overall survival for the entire cohort was 25%. The 5-year overall survival was significantly higher with earlier T-status, (pathologic tumor [pT]1/T2 vs pT3/T4; 62% vs 15%, p = 0.006). Thirteen patients who had nonregional nodal metastases without involvement of regional nodes (pN0) had a significant improvement in 5-year survival (67% vs 15%; p < 0.001). Patients with squamous cell carcinomas had higher 5-year survival compared with those with adenocarcinomas (42% vs 14%; p = 0.009). Patients treated with induction chemotherapy had prolonged 5-year survival (41%, p = 0.06) compared with those treated with adjuvant chemotherapy (11%) or no therapy (20%). Multivariate analysis demonstrated that chemotherapy treatment, squamous cell type, and early T stage (pT1/T2) are significant positive predictors of survival., Conclusions: Surgical resection for patients with esophageal cancer associated with nonregional nodal metastases results in 25% survival at five years. Squamous histology, earlier T status, and perioperative chemotherapy are independent positive predictors of long-term survival.

Background: Median sternotomy is the traditional approach used to resect anterior mediastinal masses or access the anterosuperior compartment of the mediastinum. A partial upper sternotomy is an alternative, less invasive technique. Our goal in this study is to analyze the circumstances under which partial upper sternotomy is appropriate and to determine the outcomes of these patients., Methods: From January 1994 to July 2008, 35 patients underwent partial upper sternotomy, solely or as part of a larger procedure. We analyzed these patients to determine the utility of this approach, the ability to achieve complete resection, and outcomes., Results: Of the 35 patients, 13 patients underwent resection for thymoma (9 stage I, 4 stage II), 5 for cervical node dissection, 7 for thymic hyperplasia, 3 for thyroid resection, 3 for esophagectomy, 2 for thymic cyst, 1 for bronchogenic cyst, and 1 for thymic cholesterol granuloma. Median age of patients was 51 (range 28-79) years with 54% (n = 19) males. There were no intraoperative complications or deaths within 30 days. Median length of stay was 3 days. Complete resection was possible for all patients who underwent resection for thymic masses, hyperplasia, or cystic mediastinal structures (n = 24). There were no recurrences on long-term follow-up for those with thymomas., Conclusions: Partial upper median sternotomy is a safe and effective means of accessing the anterosuperior mediastinum. It is an alternative to full sternotomy and provides a less invasive means of resecting small anterior mediastinal masses as well as accessing the thoracic inlet.

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 Fisher's 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.

Study Objective: Despite renewed interest in early detection of lung cancer, the relationship between tumor size and survival remains controversial. The objective of this study was to evaluate the relationship between size and stage in patients with T1 (< or = 3.0 cm) non-small cell lung cancer (NSCLC)., Patients and Methods: A retrospective review of a lung cancer database from 1995 to 2003 identified 503 patients with completely resected invasive NSCLC with tumors < or = 3 cm. All clinical and pathologic characteristics were recorded. Univariate associations between nodal status and other prognostic factors were explored by chi2 and t tests. The independent effect of tumor size > 2 cm vs < or = 2 cm on the risk of nodal disease was analyzed using a logistic regression model., Results: Of the 503 patients, 324 patients (64.4%) had stage IA disease, 52 patients (10.3%) had stage IB disease, 37 patients (7.4%) had stage IIA disease, 15 patients (3%) had stage IIB disease, 43 patients (8.6%) had stage IIIA disease, 24 patients (4.8%) had stage IIIB disease, and 8 patients (1.6%) had stage IV disease. One hundred patients (19.9%) had nodal metastases. The mean (+/- SD) tumor size of cases without nodal disease was 1.90 +/- 0.67 cm, compared to 2.18 +/- 0.69 cm for node-positive tumors (p = 0.0003; 95% confidence interval [CI] for mean difference, 0.13 to 0.43). Forty-eight of 308 patients (15.6%) with smaller carcinomas (< or = 2.0 cm) compared to 52 of 195 patients (26.7%) with carcinomas > 2.0 cm had nodal metastases (p = 0.002). Exploratory multivariate analysis revealed that only tumor size (< or = 2.0 cm [referent] vs > 2.0 cm) affected nodal status and thus stage (adjusted odds ratio, 2.0; 95% CI, 1.3 to 3.1; p = 0.002)., Conclusions: Primary invasive NSCLC > 2.0 cm was twice as likely to have nodal metastases than carcinomas < or = 2.0 cm. Our results suggest that in lung cancer smaller lesions may represent earlier stage disease. These results also suggest the need for further subclassification by tumor size within the current International Union Against Cancer/American Joint Committee on Cancer stage I, with tumors < 2 cm in size contained in a separate substage. This refinement may help to better clarify which patients might benefit from novel adjuvant or neoadjuvant therapeutic interventions.