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Purpose: Steroid hormones and growth factors affect lung cancer, and it is possible they act in concert to influence patient outcome.Experimental Design: Primary lung tumors and normal lung tissue were analyzed for expression and localization of estrogen receptor α and β-1 (ERα and ERβ), aromatase, progesterone receptor (PR), and epidermal growth factor receptor (EGFR).Results: Tumors expressed higher levels of ERβ compared to matched normal lung, whereas the reverse was true of PR. High cytoplasmic ERβ expression was identified as an independent negative prognostic predictor of overall survival (OS; HR = 1.67), and low total PR was identified as an independent negative predictor of time to progression (TTP; HR = 1.59). After adjusting for stage, age, sex, and smoking, combined high cytoplasmic ERβ and low total PR showed enhanced effects on OS (HR = 2.64) and on TTP (HR = 6.02). Further effects on OS were observed when EGFR expression was included (HR = 5.32). Patients with low cytoplasmic ERβ, low aromatase, low EGFR, and high total PR had shorter OS than patients with the opposite pattern (HR = 6.60). Contribution of these markers to survival showed no significant sex differences in a multivariable model. ERα was elevated in tumors but was not predictive of survival, and appears to represent a variant ERα protein that is only recognized by a C-terminal antibody.Conclusions: Hormonal and EGFR pathways together may contribute to lung cancer prognosis. Lung tumors with high ERβ-1/low PR may define patients with aggressive biology. A validation study is necessary to fully assess the predictive value of these markers. Clin Cancer Res; 17(1); 154–64. ©2010 AACR.

Supplementary Figure S1 from A Combination of Molecular Markers Accurately Detects Lymph Node Metastasis in Non–Small Cell Lung Cancer Patients

Supplementary Tables S1-S3 from A Combination of Molecular Markers Accurately Detects Lymph Node Metastasis in Non–Small Cell Lung Cancer Patients

Occult lymph node metastasis (micrometastasis) is a good prognostic indicator in non–small cell lung cancer (NSCLC) and could be used to direct adjuvant chemotherapy in stage I patients. This study was designed to evaluate molecular markers for detection of occult lymph node metastasis in NSCLC, define the best marker or marker combination to distinguish positive from benign lymph nodes, and evaluate these markers in lymph nodes from pathologically node-negative (pN0) NSCLC patients. Potential markers were identified through literature and database searches and all markers were analyzed by quantitative reverse transcription-PCR in a primary screen of six NSCLC specimens and 10 benign nodes. Selected markers were further evaluated on 21 primary NSCLC specimens, 21 positive nodes, and 21 benign nodes, and the best individual markers and combinations were identified. A combination of three markers was further validated on an independent set of 32 benign lymph nodes, 38 histologically positive lymph nodes, and 462 lymph nodes from 68 pN0 NSCLC patients. Forty-two markers were evaluated in the primary screen and eight promising markers were selected for further analysis. A combination of three markers (SFTPB, TACSTD1, and PVA) was identified that provided perfect classification of benign and positive nodes in all sample sets. PVA and SFTPB are particularly powerful in tumors of squamous and adenocarcinoma histologies, respectively, whereas TACSTD1 is a good general marker for NSCLC metastasis. The combination of these genes identified 32 of 462 (7%) lymph nodes from 20 of 68 (29%) patients as potentially positive for occult metastasis. Long-term follow-up will determine the clinical relevance of these findings.

The role of anatomic segmentectomy as an acceptable, lung parenchymal sparing alternative to pulmonary lobectomy for the small peripheral stage I lung cancer is under great scrutiny today. This is not a new consideration, particularly for the patient with impaired cardiopulmonary reserve where preservation of lung function may be a critical issue in deciding on surgical resection for local/regional control of their cancer. In this review, we discuss the oncologic issues along with past and present evidence supporting “anatomic” lung preservational surgery in the management of lung cancer.

The purpose of the current study is to determine the efficacy of a PI3K/mTOR dual inhibitor, LY3023414, on established EAC in an in vivo model.Esophageal adenocarcinoma (EAC) is a highly lethal cancer with limited treatment options. The PI3K/mTOR pathway is upregulated in EAC and may be a target for novel therapies.Esophagojejunostomy was performed on Sprague-Dawley rats to induce carcinogenesis, and LY3023414 was cyclically administered intraperitoneally between 32 and 40 weeks postsurgery to treatment animals. Magnetic resonance imaging (MRI) and histology were used to determine clinical response. Immunohistochemistry, immunofluorescence, and Western blot were used to validate apoptosis by cleaved caspase-3, proliferation by Ki67, and pathway inhibition, respectively.Mean MRI tumor volume increased by 109.2% in controls (n = 32) and decreased by 56.8% in treatment animals (n=17) (P0.01). Treatment with LY3023414 demonstrated tumor volume increase in 0% (control = 46.4%) (P0.01), decrease in 58.8% (control = 7.1%) (P0.01), and stable volume in 41.2% (control = 46.4%) (P = 0.77). EAC prevalence in controls increased by 25%; whereas, prevalence in treatment animals decreased by 29.4% (P0.01). Approximately, 75% of treatment animals presenting with residual masses on MRI had a histological response50%. Increased apoptosis by cleaved caspase-3 (P = 0.03) and decreased proliferation by Ki67 (P0.01) were demonstrated in the treatment arm, when compared with the control arm. On Western blot analysis of pathway checkpoints, p-mTOR (p=0.03) and PI3K-α (P = 0.04) were downregulated in treatment responsive residual tumors, when compared with controls.LY3023414 demonstrates efficacy against EAC in a preclinical model, establishing the rationale for clinical testing.

Standard treatment for early-stage non–small cell lung cancer has traditionally involved lobectomy. Historical data that demonstrates suboptimal results for sublobar resection compared to lobectomy have been challenged in recent years with retrospective data for patients with T1a disease. For patients who are not candidates for lobectomy, options for sublobar resection include wedge resection or anatomic segmentectomy. Segmentectomy has long been held to be a better cancer operation than wedge resection, and its role in treating early-stage lung cancer remains controversial in patients who are candidates for lobectomy. A review of available literature involving segmentectomy and possible predictors of failure for segmentectomy was performed in an attempt to clarify the role of segmentectomy for early-stage lung cancer. Current evidence is conflicting regarding the optimal scenario for sublobar resection with segmentectomy. Two large-scale randomized trials are currently addressing the question. In the meantime, certain preoperative and intraoperative considerations should be taken into account when considering segmentectomy for the treatment of early-stage non–small cell lung cancer.

Objective We hypothesize that segmentectomy is associated with similar recurrence-free and overall survival when compared with lobectomy in the setting of patients with clinical T1cN0M0 non–small cell lung cancer (NSCLC; >2-3 cm), as defined by the American Joint Committee on Cancer 8th edition staging system. Methods We performed a single-institution retrospective study identifying patients undergoing segmentectomy (90) versus lobectomy (279) for T1c NSCLC from January 1, 2003, to December 31, 2016. Univariate, multivariable, and propensity score–weighted analyses were performed to analyze the following endpoints: freedom from recurrence, overall survival, and time to recurrence. Results Patients undergoing segmentectomy were older than patients undergoing lobectomy (71.5 vs 68.8, respectively, P = .02). There were no differences in incidence of major complications (12.4% vs 11.7%, P = .85), hospital length of stay (6.2 vs 7 days, P = .19), and mortality at 30 (1.1% vs 1.7%, P = 1) and 90 days (2.2% vs 2.3%, P = 1). In addition, there were no statistical differences in locoregional (12.2% vs 8.6%, P = .408), distant (11.1% vs 13.9%, P = .716), or overall recurrence (23.3% vs 22.5%, P = 1), as well as 5-year freedom from recurrence (68.6% vs 75.8%, P = .5) or 5-year survival (57.8% vs 61.0%, P = .9). Propensity score–matched analysis found no differences in overall survival (hazard ratio [HR], 1.034; P = .764), recurrence-free survival (HR, 1.168; P = .1391), or time to recurrence (HR, 1.053; P = .7462). Conclusions In the setting of clinical T1cN0M0 NSCLC, anatomic segmentectomy was not associated with significant differences in recurrence-free or overall survival at 5 years. Further prospective randomized trials are needed to corroborate the expansion of the role of anatomic segmentectomy to all American Joint Committee on Cancer 8th Edition Stage 1A NSCLC.

Background Individualized prediction of outcomes may help with therapy decisions for patients with non-small cell lung cancer. We developed a nomogram by analyzing 17 clinical factors and outcomes from a randomized study of sublobar resection for non-small cell lung cancer in high-risk operable patients. The study compared sublobar resection alone with sublobar resection with brachytherapy. There were no differences in primary and secondary outcomes between the study arms, and they were therefore combined for this analysis. Methods The clinical factors of interest (considered as continuous variables) were assessed in a univariate Cox proportional hazards model for significance at the 0.10 level for their impact on overall survival (OS), local recurrence-free survival (LRFS), and any recurrence-free survival (RFS). The final multivariable model was developed using a stepwise model selection. Results Of 212 patients, 173 had complete data on all 17 risk factors. Median follow-up was 4.94 years (range, 0.04 to 6.22). The 5-year OS, LRFS, and RFS were 58.4%, 53.2%, and 47.4%, respectively. Age, baseline percent diffusing capacity of lung for carbon monoxide, and maximum tumor diameter were significant predictors for OS, LRFS, and RFS in the multivariable model. Nomograms were subsequently developed for predicting 5-year OS, LRFS, and RFS. Conclusions Age, baseline percent diffusing capacity of lung for carbon monoxide, and maximum tumor diameter significantly predicted outcomes after sublobar resection. Such nomograms may be helpful for treatment planning in early stage non-small cell lung cancer and to guide future studies.

Background Sublobar resection (SR) in high-risk operable patients may result in a long-term decrease in pulmonary function. We previously reported 3-month pulmonary function outcomes from a randomized phase III study of SR alone compared with SR with brachytherapy in patients with non-small cell lung cancer. We now report long-term pulmonary function after SR. Methods Pulmonary function was measured at baseline and at 3, 12, and 24 months. A decline of 10% or more from baseline in the percentage predicted forced expiratory volume of 1 percentage or in the diffusion capacity of the lung for carbon monoxide was considered clinically meaningful. The effect of study arm, tumor location, size, approach (video-assisted thoracoscopic surgery vs thoracotomy), and SR type (wedge vs segmentectomy) on pulmonary function was assessed using a Wilcoxon rank sum test. A generalized estimating equation model was used to assess the effect of each factor on longitudinal data, including all four time points. Results Complete pulmonary function data at all time points was available in 69 patients. No significant differences were observed in pulmonary function between SR and SR with brachytherapy, thus the study arms were combined for all analyses. A decline of 10% or more ( p = 0.02) in the percentage predicted forced expiratory volume in 1 second was demonstrated for lower-lobe resections at 3 months but was not at 12 or 24 months. A decline of 10% or more ( p = 0.05) in the percentage predicted diffusion capacity of the lung for carbon monoxide was seen for thoracotomy at 3 months but was not at 12 or 24 months. Conclusions Clinically meaningful declines in pulmonary function occurred after lower lobe resection and after thoracotomy at 3 months but subsequently recovered. This study suggests that SR does not result in sustained decreased pulmonary function in high-risk operable patients.

Peroral endoscopic myotomy (POEM) has been performed as a novel endoscopic procedure to treat achalasia with favorable outcome. The objective of this study was to assess the outcome of POEM in our initial series and to assess the safety and efficacy of POEM in a variety of esophageal motility-related clinical problems.This is a retrospective cross-sectional study involving all patients with esophageal motility disorders defined by the Chicago classification, who had undergone consideration for POEM at our institution. Validated questionnaires such as gastroesophageal reflux disease health-related quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease-specific health-related quality of life were obtained pre- and postoperatively.From January 2013 to October 2014, a total of 35 POEMs (achalasia n = 25, non-achalasia n = 10) were performed on 33 patients (female n = 20, male n = 13, mean age 56.9 years). There was no mortality. The rate of inadvertent mucosotomy was 17.1%. The rate of complications requiring interventions was 5.7%. During a mean follow-up period of 7 months (range 0.5-17), 92% of patients with achalasia and 75% of those with non-achalasia motility disorders had a symptomatic improvement in dysphagia. Chest pain was completely resolved in all patients with achalasia (8/8) and 80% of patients with non-achalasia (4/5). The GERD-HRQL, RSI and dysphagia scores significantly improved after POEM in patients with achalasia. There was a significant improvement in GERD-HRQL and RSI scores, and a trend toward lower dysphagia score in patients with non-achalasia.The outcome of POEM to treat achalasia and non-achalasia motility disorders is consistent with previous studies. Potential benefit of POEM includes not only its flexibility to adjust the length and location of myotomy but also the ability to extend myotomy proximally without thoracoscopy or thoracotomy. POEM can be combined with laparoscopic procedures and used as "salvage" for localized esophageal dysmotility.

Thoracic surgeons are commonly consulted to provide anterior thoracic exposure for infection and malignant neoplasms involving the thoracolumbar spine. These cases can present significant technical and management challenges secondary to the underlying pathology, associated anatomic inflammation, and impaired functional status. In this study, we review the perioperative outcomes in patients undergoing anterior spinal exposure for infection and neoplasm.130 consecutive patients (61 women, 69 men) undergoing corpectomy, debridement, or debulking for osteomyelitis (n=50) or neoplasms (n=80) with decompression/stabilization at a single institution were analyzed. Primary endpoints included morbidity, mortality, and perioperative neurologic outcomes.The mean age was 61.1 years. A cervical/sternotomy (n=8) approach was used for levels C7 to T2, thoracotomy (n=79) for levels T3 to T10, and thoracoabdominal (n=43) for T11 to L2 involvement. Primary spinal neoplasms (n=22, 16.9 %) and metastases (n=58, 44.6%) were treated with corpectomy and prosthetic stabilization and were associated with increased operative time (310 vs 243 minutes, p=0.02) and blood loss (825 vs 500 mL, p=0.002). Osteomyelitis was associated with longer hospital stays (12 vs 7 days, p0.001). The 30-day and 90-day mortality was 9.2% and 20.8%, respectively. The major complication rate was 27.7%. The median length of stay was 9 days. Surgical intervention resulted in significant improvement in pain, numbness, weakness, and bowel and bladder dysfunction.Anterior spinal exposure represents an important modality in facilitating the treatment of patients with osteomyelitis, pathologic fractures, and spinal cord compression syndromes. These procedures are associated with a significant risk of morbidity and mortality, but they are effective in achieving spinal stabilization and alleviating neurologic symptoms.

Background Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). Methods Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5 Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63 Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). Results Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. Conclusions The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.

ObjectiveThe incidence of esophageal adenocarcinoma is rapidly increasing in the western population. Despite aggressive treatment, survival after esophagectomy is suboptimal. The main objective of the present study was to evaluate the gene expression profiles in esophageal adenocarcinoma and determine their association with survival after resection.MethodsWe conducted a prospective National Institutes of Health/National Cancer Institute funded study to evaluate the prognostic significance of gene expression in patients with esophageal adenocarcinoma undergoing esophagectomy. Gene expression in tumor tissue was analyzed using high-throughput oligonucleotide arrays. The association of gene expression and overall survival was analyzed using the tail-strength statistic and Cox regression analysis. Gene signatures were constructed with semisupervised methods using principal components. A cross-validated risk score was devised by conducting 10-fold cross-validation, 100 times.ResultsWe evaluated the gene expression in 64 patients with esophageal adenocarcinoma who underwent esophagectomy. The median overall survival was 27 months (95% confidence interval 22 to not reached). After filtering, 10,214 probe sets were used for survival analysis. The tail-strength statistic for these probe sets (0.318) indicated a significant association with overall survival. Patients were classified into high- and low-risk groups, according to the gene signature. High-risk patients had a predicted median survival of 19 months, but the median was not reached for the low-risk group (P

Background Toll-like receptors (TLRs) recognize known molecules from microbes and have an established role in tumorigenesis. Using a rat model of esophageal adenocarcinoma, and human clinical samples, we investigated genes central to TLR-mediated signal transduction and characterized the esophageal microbiome across the spectrum of esophageal adenocarcinoma carcinogenesis. Methods We surgically induced bile/acid reflux in rats and their esophagi were harvested at 40 weeks post-surgery. Tissue samples from the model were selected for gene expression profiling. Additionally, for rat and human samples microbiome analysis was performed using PCR-ESI-MS-TOF technology with validation by fluorescence in situ hybridization. Results Gene expression results in the rat model indicated a significant upregulation of TLRs 1-3, 6, 7 and 9 in EAC compared to normal epithelium. PCR-ESI-MS-TOF analysis revealed a prevalence of Escherichia coli in Barrett’s esophagus (60 %) and esophageal adenocarcinoma (100 %), which was validated by fluorescence in situ hybridization. In the human clinical samples, Streptococcus pneumonia was detected in high abundance in gastroesophageal reflux disease and Barrett’s esophagus (50–70 %) in comparison to tumor adjacent normal epithelium, dysplasia, and esophageal adenocarcinoma (20–30 %). E. coli was detected in the Barrett’s esophagus and esophageal adenocarcinoma groups but was absent in the tumor adjacent normal epithelium, dysplasia, and the gastroesophageal reflux disease groups. Conclusions We demonstrated an association between the TLR signaling pathway and E. coli hinting towards possible early molecular changes being mediated by microbes in the rat model of esophageal adenocarcinoma carcinogenesis. Studies on human clinical samples also corroborate results to some extent; however, a study with larger sample size is needed to further explore this association. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2093-8) contains supplementary material, which is available to authorized users.

Background The standard treatment of stage I non-small cell lung cancer (NSCLC) is lobectomy with systematic mediastinal lymph node evaluation. Unfortunately, up to 25% of patients with stage I NSCLC are not candidates for lobectomy because of severe medical comorbidity. Methods A panel of experts was convened through the Thoracic Oncology Network of the American College of Chest Physicians and the Workforce on Evidence-Based Surgery of the Society of Thoracic Surgeons. Following a literature review, the panel developed 13 suggestions for evaluation and treatment through iterative discussion and debate until unanimous agreement was achieved. Results Pretreatment evaluation should focus primarily on measures of cardiopulmonary physiology, as respiratory failure represents the greatest interventional risk. Alternative treatment options to lobectomy for high-risk patients include sublobar resection with or without brachytherapy, stereotactic body radiation therapy, and radiofrequency ablation. Each is associated with decreased procedural morbidity and mortality but increased risk for involved lobe and regional recurrence compared with lobectomy, but direct comparisons between modalities are lacking. Conclusions Therapeutic options for the treatment of high-risk patients are evolving quickly. Improved radiographic staging and the diagnosis of smaller and more indolent tumors push the risk-benefit decision toward parenchymal-sparing or nonoperative therapies in high-risk patients. Unbiased assessment of treatment options requires uniform reporting of treatment populations and outcomes in clinical series, which has been lacking to date.

Single cell analysis and cell sorting has enabled the study of development, growth, differentiation, repair and maintenance of "liquid" tissues and their cancers. The application of these methods to solid tissues is equally promising, but several unique technical challenges must be addressed. This report illustrates the application of multidimensional flow cytometry to the identification of candidate stem/progenitor populations in non-small cell lung cancer and paired normal lung tissue. Seventeen paired tumor/normal lung samples were collected at the time of surgical excision and processed immediately. Tissues were mechanically and enzymatically dissociated into single cell suspension and stained with a panel of antibodies used for negative gating (CD45, CD14, CD33, glycophorin A), identification of epithelial cells (intracellular cytokeratin), and detection of stem/progenitor markers (CD44, CD90, CD117, CD133). DAPI was added to measure DNA content. Formalin fixed paraffin embedded tissue samples were stained with key markers (cytokeratin, CD117, DAPI) for immunofluorescent tissue localization of populations detected by flow cytometry. Disaggregated tumor and lung preparations contained a high proportion of events that would interfere with analysis, were they not eliminated by logical gating. We demonstrate how inclusion of doublets, events with hypodiploid DNA, and cytokeratin+ events also staining for hematopoietic markers reduces the ability to quantify epithelial cells and their precursors. Using the lung cancer/normal lung data set, we present an approach to multidimensional data analysis that consists of artifact removal, identification of classes of cells to be studied further (classifiers) and the measurement of outcome variables on these cell classes. The results of bivariate analysis show a striking similarity between the expression of stem/progenitor markers on lung tumor and adjacent tumor-free lung.

Objectives Energy-based tissue fusion technology is being increasingly used for vascular division in numerous intra-abdominal applications. Very few data, however, are available regarding the application of this technology in the chest during anatomic lung resection. In the present review, we evaluated the use of energy-based fusion and lung sealants during anatomic lung resection. Methods We performed a review of case series and published studies to evaluate the use of energy-based coagulative fusion technology and lung sealants during anatomic lung resection. We then used energy-based coagulative fusion technology during anatomic lung resection (segmentectomy or lobectomy) in 316 cases from 2008 to 2011. Two energy applications were applied to the arterial and venous branches before vessel division. Results In the first 12 cases, we used a device with a small curved jaw (range, 3.3-4.7 mm). Two partial venous dehiscences were noted and controlled intraoperatively. For the remaining cases, we used a larger jaw (6 mm × 22 mm) with no arterial or venous dehiscence occurring (vessels ranged from 0.4 to 1.2 cm). Autologous or synthetic tissue sealants applied to the parenchymal staple lines might reduce the severity and duration of perioperative air leaks. Suture line buttressing with pericardial or absorbable biosynthetic polyester strips might reduce the severity of air leaks in patients with severe emphysema undergoing anatomic lung resection or lung volume reduction surgery. Conclusions The bipolar tissue fusion system provides a safe and effective technique for the division of the pulmonary arterial and venous branches during anatomic lung resection. Surgical sealants and buttressing adjuncts might reduce perioperative air leak potential.

Background Anatomic segmentectomy is a versatile sublobar resection approach that can be both diagnostic and therapeutic in the setting of the indeterminate pulmonary nodule (IPN), metastasectomy, as well as small, peripheral cancers. We analyzed the clinical indications and perioperative outcomes after anatomic segmentectomy and explored its utility in the diagnosis and treatment of IPNs and small stage IA lung cancers. Methods This study is a retrospective review of 785 consecutive patients undergoing anatomic segmentectomy from 2002 to 2010. Primary outcome variables include perioperative course, morbidity, mortality, recurrence patterns, and survival. Results Surgical indications included IPN (62.4%), known lung cancer (27.6%), suspected metastasis (4.1%), bullous disease (3.7%), or other (2.2%). Video-assisted thoracic surgery was employed in 468 (59.6%) and open thoracotomy in 317 (40.4%) patients. Median length of stay was 6 days. Overall complication rate was 34.9%. Thirty-day mortality was 1.1%. Among 490 patients with an IPN, 381 (77.7%) were found to have lung cancer, 41 (8.4%) metastatic cancer, and 68 (13.9%) benign disease. Among patients with pathologic stage IA lung cancer, there was no difference in recurrence rates (14.5% vs 13.9%) or 5-year freedom from recurrence estimates (78% in each group, p = 0.738) when comparing segmentectomy and lobectomy. Conclusions Anatomic segmentectomy provides acceptable morbidity and mortality when approaching the IPN. Cancer is identified in 86% of lesions. Complete surgical resection can be achieved with generous parenchymal margins and thorough nodal staging for small, peripheral stage IA non-small cell lung cancer. The use of anatomic segmentectomy should be considered in this era of competing image-guided diagnostic and therapeutic approaches to peripheral lung pathology.

ObjectiveAnatomic segmentectomy may achieve results comparable to lobectomy for early-stage non–small cell lung cancer. The 7th edition of the AJCC Cancer Staging Handbook stratified the previous T1 tumor designation into T1a and T1b subsets, which still define stage 1A node-negative non–small cell lung cancer. We are left to hypothesize whether this classification may aid in directing the extent of surgical resection. We retrospectively reviewed our anatomic segmentectomy and lobectomy management of stage 1A non–small cell lung cancer to determine differences in survival and local recurrence rates based on the new stratification.MethodsWe performed a retrospective review of 429 patients undergoing resection of pathologically confirmed stage 1A non–small cell lung cancer via lobectomy or anatomic segmentectomy. Primary outcome variables included mortality, recurrence, and survival. Recurrence-free and cancer-specific survivals were estimated using the Kaplan–Meier method.ResultsPatients undergoing segmentectomy were older than patients undergoing lobectomy (mean age 69.2 vs 66.8 years, P

We have tested PJ34, a potent inhibitor of poly(ADP-ribose) polymerase (PARP), against various lung cancer cell lines (Calu-6, A549, and H460) and normal human bronchial epithelial cells (HBECs). While using WST1 dye assay, lung cancer cells exhibited LD(50) values of approximately 30 μM PJ34 (72-hr assay). Molecular data showed that the effect of PJ34-induced apoptosis on lung cancer cells occurs via a caspase-dependent pathway. The present study has clearly shown that (a) PARP inhibitor can independently kill tumor cells, (b) caspase-3 has modest influence on PARP-inhibitor-mediated cancer-specific toxicity, and (c) a pan-caspase inhibitor decreases the apoptotic effect of PJ34.

Background The recent initiation of screening protocols and greater utilization of computed tomography has led to an increasing proportion of non-small cell lung cancer (NSCLC) patients presenting with subcentimeter stage IA tumors. The aim of this study was to compare the oncologic outcomes of lobectomy, segmentectomy, and wedge resection in patients with NSCLC tumors 1 cm or less in diameter. Methods Data were extracted from medical records of patients undergoing surgical resection for stage IA NSCLC and a pathologically confirmed tumor diameter measuring 1 cm or less. Primary oncologic outcomes were disease recurrence and disease-free survival. Statistical comparisons were performed using Fisher's exact test and unpaired t test. Kaplan-Meier curves were compared using the log rank test. Significance was defined as a two-tailed p value less than 0.05. Results A total of 107 patients underwent complete (R0) surgical resection for stage IA NSCLC 1 cm or less in diameter (lobectomy, 32; segmentectomy, 40; wedge, 35). Age, sex distribution, tumor size, and histology were similar between groups. There was 1 perioperative mortality in the lobectomy group (3%). At a mean follow-up of 42.5 months, overall disease recurrence was equivalent, occurring in 3 lobectomy patients (9%), 4 segmentectomy patients (10%), and 3 wedge resection patients (9%; p = 0.99). Estimated 5-year disease-free survival was comparable among cohorts (lobectomy, 87%; segmentectomy, 89%; wedge, 89%; p >0.402). Conclusions Sublobar resections are associated with oncologic outcomes that are comparable to those of lobectomy for subcentimeter stage IA NSCLC, suggesting that they may be appropriate surgical interventions in this patient cohort. The validity of these observations needs to be assessed in a prospective setting.

Background Lymph node status is a major determinant of stage and survival in patients with lung cancer; however, little information is available about the expected yield of a mediastinal lymphadenectomy. Methods The American College of Surgeons Oncology Group Z0030 prospective, randomized trial of mediastinal lymph node sampling vs complete mediastinal lymphadenectomy during pulmonary resection enrolled 1,111 patients from July 1999 to February 2004. Data from 524 patients who underwent complete mediastinal lymph node dissection were analyzed to determine the number of lymph nodes obtained. Results The median number of additional lymph nodes harvested from a mediastinal lymphadenectomy following systematic sampling was 18 with a range of one to 72 for right-sided tumors, and 18 with a range of four to 69 for left-sided tumors. The median number of N2 nodes harvested was 11 on the right and 12 on the left. A median of at least six nodes was harvested from at least three stations in 99% of patients, and 90% of patients had at least 10 nodes harvested from three stations. Overall, 21 patients (4%) were found to have occult N2 disease. Conclusions Although high variability exists in the actual number of lymph nodes obtained from various nodal stations, complete mediastinal lymphadenectomy removes one or more lymph nodes from all mediastinal stations. Adequate mediastinal lymphadenectomy should include stations 2R, 4R, 7, 8, and 9 for right-sided cancers and stations 4L, 5, 6, 7, 8, and 9 for left-sided cancers. Six or more nodes were resected in 99% of patients in this study. Trial registry ClinicalTrials.gov; No.: NCT00003831; URL: clinicaltrials.gov

Background The density of tumor-infiltrating lymphocytes (TIL) in lung cancer is variable and may have an impact on disease course. We reviewed the histology of lobectomy specimens from patients with pathologic stage IA-IB non-small-cell lung cancer to determine the impact of TILs on recurrence and survival. Materials and methods Two hundred nineteen lobectomies performed between 2002 and 2005 for stage IA-IB non-small-cell lung cancer were reviewed. Patients were stratified according to tumor size. Infiltrating patterns were graded as follows: group 1 (none to mild infiltrate) or group 2 (moderate to severe infiltrate). Recurrence rates and disease-free survival were compared between groups in each tumor size cohort. Results A higher density of TILs was associated with lower disease recurrence (60%, group 1 versus 21%, group 2, P = 0.02) and improved 5-y disease-free survival (35.9%, group 1 versus 75.6%, group 2, P = 0.04) in patients with tumors 5cm or greater in diameter. There were no correlations in patients with smaller tumors. Conclusions A higher degree of TILs within large node-negative non-small-cell lung cancer correlates with decreased risk of disease recurrence and improved disease-free survival. This subset of patients with tumor infiltration needs to be examined more closely with regards to outcomes of adjuvant chemotherapy.

Objective The minimally invasive, video-assisted thoracoscopic surgical (VATS) approach to resection of the thymus is frequently practiced for benign disease; however, a VATS approach for thymoma remains controversial. The objective of the present study was to evaluate the feasibility of VATS thymectomy for the treatment of early-stage thymoma and to compare the outcomes with those after open resection. Methods A retrospective review of 40 patients who underwent surgical resection of early-stage thymoma during a 12-year period was conducted. Data on patient characteristics, morbidity, recurrence, and survival were collected. The primary endpoint studied was overall survival. Results Of the 40 patients, 14 underwent thymectomy for stage I and 26 for stage II thymoma; 19 were men and 21 were women (median age, 64 years; range, 35–86 years). Open thymectomy was performed in 22 patients, and VATS was performed in 18. The operative mortality rate was 0%. The tumor stage and number of patients undergoing adjuvant radiotherapy were comparable in both surgical groups. The median length of hospital stay was shorter in the VATS group (3 days) than in the open group (5 days) ( P = .0001). The median follow-up was 36 months. No significant differences were found in the estimated recurrence-free and overall 5-year survival rates (83%–100%) between the 2 groups. Conclusions VATS of early-stage thymoma appears safe and feasible and was associated with a shorter hospital stay. The oncologic outcomes were comparable in the open and VATS groups during intermediate-term follow-up. Additional follow-up is required to evaluate the long-term results of thoracoscopic thymectomy for early-stage thymoma.

A patient undergoing radical extrapleural pneumonectomy for epithelioid malignant mesothelioma developed acute paraplegia postoperatively related to long-segment spinal cord ischemia. The usual area of concern for this complication is the T9 to T12 area where the artery of Adamkiewicz is most likely to originate. In this patient, there was ligation of only upper thoracic, ipsilateral segmental arteries from the T3 to T6 level, yet he still developed paraplegia. Our hypothesis is variant mid-thoracic vascular anatomy. Previously unreported, to our knowledge, this should be understood as a rare complication of this surgery.

Objectives Mechanical stapling devices have been established as the mainstay of therapy in the selective isolation and division of bronchial and vascular structures during anatomic lung resection. Few data are available regarding the application of energy-based tissue fusion technology during anatomic lung resection. In the present study, we evaluated the use of energy-based instruments for the division of the pulmonary arterial and venous branches during anatomic lung resection. Methods Anatomic lung resection (segmentectomy or lobectomy) was performed using energy-based coagulative fusion technology. A low-profile jaw can be used to facilitate dissection in both open and video-assisted thoracic surgery cases, applying a seal 6 mm wide by 22 mm in length. Two energy applications were applied to the arterial and venous branches before vessel division. Results The bipolar tissue fusion system was used in 211 patients between 2008 and 2010 (104 lobectomies and 107 anatomic segmentectomies). Initially, we used a device with a smaller, curved jaw (n = 12), producing a 3.3- to 4.7-cm seal. No arterial dehiscences and 2 partial venous dehiscences that were recognized and controlled intraoperatively occurred. For the remaining cases, we used a new device with a larger jaw that applied a seal 6 mm wide by 22 mm in length. No arterial or venous dehiscences (vessel size range, 0.4-1.2 cm) occurred. Conclusions The bipolar tissue fusion system provided safe and reliable control of pulmonary arterial and venous branches during anatomic lung resection. The use of energy-based tissue fusion technology represents a reasonable alternative to mechanical stapling devices during anatomic lung resection.

Patients with clinical stage I lung cancer can be considered as arising from three treatment groups: (1) good-risk patients, who are usually treated with lobectomy; (2) high-risk patients, who are usually treated with sublobar (segmental or wedge) resection; and (3) medically inoperable patients, who have traditionally been treated with external beam radiation. Stereotactic body radiation therapy and radiofrequency ablation are two approaches that are gaining increasing popularity for medically inoperable patients. Some have even argued that stereotactic body radiation therapy may be equivalent to lobectomy because of equivalent local control. This assumption is incorrect, because the definitions of local control in the surgical, radiation oncology, and radiology literature are not the same. At best, stereotactic body radiation therapy and radiofrequency ablation can only approximate a wedge resection if it is assumed that 100% tumor destruction has occurred. Lymph node dissection and sampling can also be undertaken at the time of sublobar resection, potentially improving outcomes and allowing identification of unsuspected nodal disease. Despite this, stereotactic body radiation therapy and radiofrequency ablation may be clinically equivalent to sublobar resection for the high-risk patient because of lower procedural morbidity and more rapid return to normal function; however, this has not yet been determined in prospective studies. We review current data on oncologic and secondary outcomes such as morbidity and effect on pulmonary function to help define which therapy is best.

Lung cancer is the most common cause of cancer related mortality in the United States. Surgical resection with a lobectomy is the standard treatment for Stage I non-small cell lung cancer (NSCLC). With an aging population however, there are a significant number of patients who have other co-morbidities that preclude surgical resection. Image-guided radiofrequency ablation is a new emerging modality of treatment which may be applicable in this high-risk group of patients. In this article, we review the principles of radiofrequency ablation, the common devices in use, the results of ablate and resect studies, future directions, and the results of treatment for Stage I non-small cell lung neoplasm.

Lung cancer is the most common cause of cancer-related mortality in the United States. Surgical resection remains the standard treatment for early stage, non-small cell lung cancer, and limited pulmonary metastases. However, many patients with resectable disease have significant co-morbidities which preclude surgical resection. Radiofrequency and microwave ablation are emerging modalities of treatment for these high-risk patients. Here, we review the principles, common devices in use, and treatment results of ablative therapy for lung tumors.

COPD is a heterogeneous disorder with clinical assessment becoming increasingly multidimensional. We hypothesized HRCT phenotype would strongly influence clinical outcomes including health status, exacerbation frequency, and BODE. COPD subjects were characterized via the SF-12, SGRQ, MMRC, physiologic testing, and standardized volumetric chest HRCT. Visual semi-quantitative estimation of bronchial wall thickness (VBT) and automated quantification of emphysema percent and bronchial wall thickness were generated. Multivariate modeling compared emphysema severity and airway abnormality with clinical outcome measures. Poisson models were used to analyze exacerbation frequency. SGRQ and SF-12 physical component scores were influenced by FEV(1)% predicted, emphysema percent, and VBT. VBT scores > 2 (scale 0-48) were associated with increased exacerbation frequency (p = 0.009) in the preceding year adjusting for age, gender, emphysema percent, smoking history and FEV(1)% predicted, although this effect was attenuated by age. Emphysema percent correlated with total BODE score in unadjusted (r = 0.73; p < 0.0001) and adjusted (p < 0.0001) analyses and with BODE individual components. HRCT provides unique COPD phenotyping information. Radiographic quantification of emphysema and bronchial thickness are independently associated with SGRQ and physical component score of the SF-12. Bronchial thickness but not emphysema is associated with exacerbation frequency, whereas emphysema is a stronger predictor of BODE and its systemic components MMRC, 6MWT, and BMI. Future research should clarify whether CT parameters complement BODE score in influencing survival.

Central lung cancers with pulmonary hilar involvement can pose a technical challenge when a lateral thoracotomy is used. Proximal vascular control and pulmonary vascular dissection from this approach can be challenging and potentially dangerous. We describe the use of a Chamberlain anterior minithoracotomy as an alternative approach for safe and reliable access to the pulmonary hilum. One hundred two consecutive patients undergoing the Chamberlain approach were identified through retrospective chart review from 2002 to 2009. The supine position was used, thus reducing the likelihood of down-lung syndrome. An 8-cm anterior thoracotomy was performed over the second interspace along the line of the pectoral fibers, with preservation of the mammary artery medially and the thoracoacromial neurovascular bundle laterally. Primary outcome variables included hospital course, complications, and mortality rate. The mean age was 64.8 years (range, 20–89 years). Sex ratio (female:male) was 44:58. Neoadjuvant therapy was used in 43 patients (42.2%). Proposed resections were successful in 101 (99%) of 102 patients. Conversion to hemiclamshell was required in 1 patient for vascular control. Three perioperative deaths (2.9%; two pneumonectomies, one lobectomy) occurred. The Chamberlain mini anterior thoracotomy provides direct access to the pulmonary hilum, facilitating dissection and vascular control for large and central tumors. Reduced perioperative pain and down-lung syndrome compared to lateral approaches can be achieved. Muscle function is preserved, and intrapericardial/hilar access is expeditious. This approach enhances hilar access and avoids the vascular control and hilar exposure challenges inherent with lateral thoracotomy.

Background Surgical resection is the standard of care for patients with resectable non–small cell lung cancer or selected patients with pulmonary metastases. However, for high-risk patients radiofrequency ablation (RFA) may offer an alternative option. The objective of this study was to evaluate computed tomography–guided RFA for high-risk patients and report our initial experience in 100 consecutive patients by a thoracic surgical service. Methods Medically inoperable patients were offered RFA. Thoracic surgeons evaluated and performed RFA under computed tomography guidance. Patients were followed in the thoracic surgery clinic. The primary end point evaluated was overall survival. Results One hundred patients underwent image-guided RFA for lung neoplasm (40 men, 60 women; median age, 73.5 years; range, 26 to 95 years). Forty-six patients (46%) with primary lung neoplasm, 25 patients (25%) with recurrent cancer, and 29 patients (29%) with pulmonary metastases underwent RFA. The mean follow-up for alive patients was 17 months. The median overall survival for the entire group of patients was 23 months. The probabilities of 2-year overall survival for the entire group, primary lung cancer patients, recurrent cancer patients, and metastatic cancer patients were 49% (95% confidence interval, 37 to 60), 50% (95% confidence interval, 33 to 65), 55% (95% confidence interval, 25 to 77), and 41% (95% confidence interval, 19 to 62), respectively. Conclusions Our experience indicates that image-guided RFA done by the thoracic surgeons is feasible and safe in high-risk patients with lung neoplasm with reasonable results in patients who are not fit for surgery. Thoracic surgeons can perform RFA safely, and should continue to investigate this new image-guided modality that may offer an alternative option in medically inoperable patients.

Background Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with minimal mediastinal contamination at the time of diagnosis could be managed successfully with nonoperative treatment modalities. Methods We performed a retrospective review of 119 consecutive patients with esophageal perforation from 1998 to 2008. Demographics, cause of perforation, clinical presentation, diagnostic methods, and management results were evaluated. The decision to operate was based on the extent of mediastinal contamination and systemic sepsis rather than cause of perforation. Results Median time to diagnosis among all patients was 12 hours (range, 1–120). Spontaneous (Boerhaave's) perforation occurred in 44 (37%) patients. Iatrogenic perforations constituted the remaining patients (n = 75). After instrumental perforation, 9 patients (13%) required esophagectomy, 48 patients were managed with repair and drainage, and the remaining 18 were managed nonoperatively. All 34 patients undergoing operative therapy for spontaneous perforations were treated with esophageal repair. Overall mortality was 14%, with intrathoracic perforations having 18% mortality, cervical 8%, and gastroesophageal junction 3%. Patients undergoing nonoperative therapy had a shorter hospitalizations (13 vs 24 days), fewer complications (36% vs 62%), and less mortality (4% vs 15%) compared with those undergoing operative intervention. Conclusion An approach to esophageal perforation based on injury severity and the degree of mediastinal and pleural contamination is of paramount importance. Although operative management remains the standard in the majority of patients with esophageal perforation, nonoperative management may be successfully implemented in selected patients with a low morbidity and mortality if favorable radiographic and clinical characteristics are present.

Background The diagnostic yield and accuracy of new approaches to diagnose cancer should focus on comparison with established surgical techniques. Our objective was to evaluate the diagnostic performance of endobronchial ultrasound (EBUS) to detect cancer in patients with radiographically abnormal mediastinal lymph nodes. Methods The medical records of patients who underwent EBUS and had abnormal mediastinal lymph nodes (short-axis >1 cm and [or] positron emission topography-positive) over a 25 month period at the University of Pittsburgh were reviewed. Demographic and clinical data, cytology, and pathology results were entered in a database and analyzed. Results A total of 172 patients [male to female=1.8:1; median age, 67 years (range, 20 to 90]) were included. The diagnostic yield of EBUS cytology was 79.7% (137 of 172). Pathologic testing was available in 68% (117 of 172) and 82% (96 of 117) had a diagnostic EBUS. The diagnostic accuracy of EBUS was 91.7%. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were 88.1% (95% confidence interval [CI], 77.3 to 94.3), 100% (95% CI, 85.9 to 100), 100% (95% CI, 92.4 to 100), and 80.6% (95% CI, 63.4 to 91.2), respectively. In 67 patients who had a suspected or biopsy-proven primary lung cancer, diagnostic yield was 86.6% and accuracy was 94.8%. In this subgroup the sensitivity, specificity, PPV, and NPV were 93% (95% CI, 76.5 to 98.9), 100% (95% CI, 69.9 to 100), 100% (95% CI, 85 to 100), and 83.3% (95% CI, 56.2 to 97.5). Conclusions Diagnostic performance data support the clinical usefulness of EBUS in the evaluation of patients with a radiographically abnormal mediastinum. It should be considered complementary to mediastinoscopy rather than substitutive.

Recent adjuvant chemotherapy trials after resection of stage II and III non-small cell lung cancer (NSCLC) have identified important survival differences among patients with immunohistochemical evidence suggesting platinum resistance. No clinical information exists regarding the impact upon survival of patients treated with platinum agents who exhibit cellular evidence of their tumors’ resistance to platinum. We evaluated the utility of the extreme drug resistance (EDR) assay to predict mortality among a consecutive group of stage II through IV NSCLC patients receiving adjuvant or definitive platinum-based chemotherapy after resection or surgical biopsy. The Extreme Drug Resistance (EDR) Assay is a clinically validated cellular proliferation assay used to test tumors for chemotherapy drug resistance. Based on response in the EDR assay, tumor specimens from stage II through IV NSCLC patients were segregated into three groups: extreme drug resistant (EDR), intermediate drug resistant (IDR), and low drug resistant (LDR). Patient survival was evaluated after platinum-based chemotherapy. Platinum IDR/EDR was statistically significant in predicting shorter overall survival (29.8 months vs. 15.6 months) among platinum IDR/EDR-resistant patients compared with LDR patients (P = 0.047). Median survival was 16.6 months for patients with IDR/EDR to platinum and any other second agent of doublet therapy compared with patients with LDR to any platinum-based doublet where median survival was not achieved (P = 0.0268). This is the first study to demonstrate the utility of the EDR assay to predict poor clinical outcome when platinum-based therapy is used to treat patients with biological evidence of tumor resistance to platinum. These data corroborate the finding of recent studies evaluating possible molecular correlates to poor response to specific chemotherapeutic agents.

The management of Barrett's esophagus with high-grade dysplasia is controversial. The standard of care has traditionally been esophagectomy. However, a number of treatment options aimed at esophageal preservation are increasingly being utilized by many centers. These esophageal-sparing approaches include endoscopic surveillance, mucosal ablation, and endoscopic mucosal resection. In this guideline we review the best evidence supporting these commonly used strategies for high-grade dysplasia to better define management and guide future investigation.

Signal pathway inhibitors (SPI) are designed to act synergistically with conventional cytotoxic drugs to control cancer progression. The objective of this study was to evaluate the effect of various SPI, both alone and in combination with cisplatin, on three different non-small cell lung cancer (NSCLC) cell lines.Cell lines (A549, 201T, 273T) representing NSCLC were treated for 72 h in the presence or absence of inhibitors to PI3K (LY-294002; Tocris Bioscience, Ellisville, MO), BCL-2 (Gossypol; Sigma-Aldrich, St. Louis, MO), Cox-2 (NS-398 [Sigma-Aldrich] or Celecoxib [Pfizer]), MAPK (U0126 [Sigma-Aldrich]), and EGFR (Iressa; AstraZeneca, Macclesfield, United Kingdom) both alone and in combination with 10 or 30 mum cisplatin (Sigma-Aldrich) (18 possible regimens for each cell line). MTT assay (Trevigen, Gaithersburg, MD) was used to measure cytotoxicity. Controls were represented by cells with either a pure culture medium (monotherapy regimen control) or culture medium with the corresponding dose of cisplatin (combination regimen control). Unpaired t-test was used to classify response to therapy as highly sensitive (P0.01), sensitive (0.01or = P0.05), or resistant (Por = 0.05). Concordance was defined as a similar response category between cell lines.The concordance rate was 50% between each of the three cell lines when SPI were used as monotherapy. In combination regimens, the concordance rates were 33% (A549 and 273T), 17% (A549 and 201T), and 75% (273T and 201T). The 273T cells were most susceptible to therapy, having 11 (61%) highly sensitive responses, whereas A549 cells were least susceptible with 14 (78%) resistant responses.There is a substantial degree of variability between NSCLC cell lines in response to SPI, both alone and in combination with cisplatin.

Background Anatomic segmentectomy for stage I non-small cell lung cancer (NSCLC) offers the potential of surgical cure with preservation of lung function. This may be of particular importance in elderly NSCLC patients with declining cardiopulmonary status and a limited life expectancy. Methods The study compared outcomes of 78 elderly patients (aged > 75 years) with stage I NSCLC undergoing segmentectomy and 106 undergoing lobectomy for stage I NSCLC from 2002 to 2007. Primary outcome variables included perioperative morbidity and mortality, hospital course, recurrence patterns, and survival. Results Age, gender, tumor histology, and surgical approach were similar between groups. Comorbidities were similar except for a higher incidence of chronic obstructive pulmonary disease and diabetes in segmentectomy patients. The tumors in the lobectomy group were significantly larger (3.5 vs 2.5 cm, p = 0.0001). Operative mortality was 1.3% for segmentectomy and 4.7% for lobectomy. Segmentectomy patients had fewer major complications (11.5% vs 25.5%, p = 0.02). There were no differences in median hospitalization (7 vs 6 days). The estimated overall survival at 2, 3, and 5 years was 76%, 69%, and 46% for segmentectomy patients and 68%, 59%, and 47% for lobectomy patients ( p = 0.28). The 5-year disease-free survival was equivalent (segmentectomy, 49.8%; lobectomy, 45.5%; p = 0.80). Conclusions Anatomic segmentectomy can be performed safely in elderly patients with early-stage NSCLC. This approach is associated with reduced perioperative complications and comparable oncologic efficacy compared with lobectomy in older patients with a limited life expectancy.

Objectives Surgical resection is the preferred treatment in selected patients with pulmonary metastases. In high-risk patients, radiofrequency ablation (RFA) may offer an alternative option. RFA may be used alone or combined with surgical resection as a lung parenchymal-sparing approach. Our objectives were to evaluate the intermediate term outcomes after RFA and to determine the prognostic variables associated with outcome in patients with pulmonary metastases. Methods Thoracic surgeons evaluated and performed RFA under computed tomography (CT) guidance or combined with surgical resection. Patients were monitored in the thoracic surgery clinic for recurrence and survival. Results Twenty-two patients (10 men, 12 women; median age, 63 years [range, 37 to 88]) underwent RFA. The primary cancer was colorectal in 9 (41%), renal in 2 (9%), sarcoma in 4 (18%), and other in 7 (32%). CT-guided RFA was the sole treatment in 17 patients (77%) and combined with surgical resection in 5 (23%). No procedurally related deaths occurred. At a mean follow-up of 27 months (range, 13.3 to 53.6 months), 9 patients are alive. The median survival was 29 months (95% confidence interval, 9.1 to 33.8). Lesion size was an important prognostic variable associated with overall and disease-free survival ( p ω 0.05). Conclusions RFA is safe in this group of pulmonary metastases patients, with reasonable results. Surgical resection remains the standard for resectable patients, but RFA offers an alternative in selected patients or may be used as a parenchymal-sparing approach in combination with surgical resection in selected patients.

Background The management of non-small cell lung cancer (NSCLC) depends on the stage, with a satellite nodule in the same lobe being classified as T4 stage IIIB even in node negative patients. Controversy exists as to the optimal management of these patients. Our objectives were to evaluate the outcomes in surgically resected patients with a T4 satellite lesion and to analyze the prognostic factors associated with outcome. Methods Patients who underwent resection for T4 (satellite nodule) N0-2M0 were identified. Patients with pure bronchoalveolar carcinoma were excluded. The primary endpoint studied was overall survival. Multiple covariates were analyzed for association with survival and recurrence. Results A total of 51 T4 N0-2 patients (men 22, women 29; median age 71 years [48 to 87]) underwent resection over a 7-year period. At a median follow-up of 26.4 months the estimated 5-year overall survival was 26% (95% confidence interval [CI] 14% to 50%; median survival 25.2 months). The estimated 5-year overall survival for T4 N0 patients was 40% (95% CI 23% to 68%; median survival 34.8 months). Size of the primary tumor, histology, and nodal status were significantly associated with overall survival; size and nodal status were significantly associated with disease-free survival. Conclusions Our results indicate that T4 (satellite nodule) N0 patients experienced excellent survival after surgical resection. These data support surgical resection in node negative patients. Size, histology, and nodal status were important prognostic variables associated with outcome. Consideration should be given to multimodality treatment in patients with adverse prognostic features. Further larger multiinstitutional studies are required to validate these findings.

ObjectiveThe study objective was to determine the clinical usefulness and accuracy of endobronchial ultrasound-guided needle aspiration of mediastinal and hilar lymph nodes.MethodsA retrospective analysis of a thoracic surgery unit's experience was performed.ResultsIn a period of 19 months, 75 patients underwent the procedure (mean age = 65.5 ± 1.6 years; male to female = 2:1) most commonly for mediastinal lymphadenopathy in the setting of diagnosed or suspected lung cancer. It was diagnostic in 68.9% after rapid on-site evaluation and 74.3% after final cytologic examination. The rapid on-site evaluation and final cytology results were discordant in 16.2% (P < .001). In 50 cases, the needle aspirate cytology could be compared with pathology results. The sensitivity and specificity for the diagnosis of cancer were 85% and 100%, respectively. The false-negative rate endobronchial ultrasound cytology was 8.1%. Mediastinal lymph node station 7 was most commonly biopsied. The stations with the highest diagnostic yield were: 11R, 3, 10L, and 7. Of the patients with a positive positron emission tomography scan with suspected clinical stage III lung cancer, cancer was downstaged in 40% after endobronchial ultrasound.ConclusionEndobronchial ultrasound-guided needle aspiration is a clinically useful minimally invasive option for lung cancer staging and evaluation of mediastinal lymphadenopathy. The procedure should be considered complementary to mediastinoscopy.