Bryan A. Whitson

Surgery for Early-Stage Non-Small Cell Lung Cancer: A Systematic Review of the Video-Assisted Thoracoscopic Surgery Versus Thoracotomy Approaches to Lobectomy

Video-assisted thoracoscopic surgery (VATS) for lobectomy has been touted to provide superior outcomes, compared with thoracotomy, for patients with early-stage non-small-cell lung cancer (NSCLC). However, supporting data are limited to case series and small observational studies. We hypothesized that a systematic review of the literature would enable a more objective evaluation of the evidence in order to determine the potential superiority of the VATS approach, compared with thoracotomy, in terms of short-term morbidity and long-term survival. To identify relevant articles for inclusion in our analysis, we performed a systematic review of the MEDLINE database. We looked for randomized controlled trials, observational studies, and case series that reported outcomes after VATS or thoracotomy lobectomy for NSCLC. For statistical testing, we used a two-sided approach (alpha = 0.05) under the hypothesis that VATS lobectomy is superior to thoracotomy lobectomy. We screened 17,923 studies. After independent review of the abstracts by 2 reviewers, we included 39 studies (only one randomized controlled trial) in our analysis. In aggregate, these 39 studies involved 3256 thoracotomy and 3114 VATS patients. The characteristics of the two groups were not significantly different. Compared with thoracotomy, VATS lobectomy was associated with shorter chest tube duration, shorter length of hospital stay, and improved survival (at 4 years after resection), all statistically significant. Compared with lobectomy performed by thoracotomy, VATS lobectomy for patients with early-stage NSCLC is appears to favor lower morbidity and improved survival rates.

Survival After Lobectomy Versus Segmentectomy for Stage I Non-Small Cell Lung Cancer: A Population-Based Analysis

BACKGROUND Data comparing survival after lobectomy versus that after segmentectomy for stage I non-small cell lung cancer (NSCLC) are limited to single-institution observational studies and 1 clinical trial. We sought to determine if lobectomy offers a survival advantage over segmentectomy for stage I NSCLC based on population-based data. METHODS Using the Surveillance Epidemiology and End Results (SEER) database (1998 to 2007), we identified patients who underwent either anatomic segmentectomy or lobectomy. Wedge resections were excluded. Analysis was limited to patients with stage I adenocarcinoma or squamous cell carcinoma. After stratifying patients based on tumor size (less than or equal to 2.0 cm, 2.1 to 3.0 cm, and 3.1 to 7.0 cm), we assessed for association between extent of resection and survival using the Kaplan-Meier method. To adjust for potential confounding variables, we used Cox proportional hazards regression models. RESULTS There were 14,473 patients who met our inclusion criteria. Lobectomy conferred superior unadjusted overall (p < 0.0001) and cancer-specific (p = 0.0053) 5-year survival compared with segmentectomy. Even after adjusting for patient factors, tumor characteristics, and geographic location, we noted that patients who underwent lobectomy had superior overall and cancer-specific survival rates, regardless of tumor size. Squamous cell histologic type, male sex, low lymph node counts, and increasing age, tumor size, and grade were all independent negative prognostic factors. CONCLUSIONS Using a population-based data set, we found that lobectomy confers a significant survival advantage compared with segmentectomy. Our results provide additional evidence supporting the role of lobectomy as the standard of care for resection of stage I NSCLC regardless of tumor size.

Endobronchial Ultrasound-Guided Fine-Needle Aspiration of Mediastinal Lymph Nodes: A Single Institution's Early Learning Curve

BACKGROUND The gold standard for mediastinal lymph node evaluation is mediastinoscopy, which is invasive and allows access to only a limited number of mediastinal lymph node (MLN) stations (1, 2, 3, 4, and 7). Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) is emerging as a useful, less invasive technique that offers access to a wider range of MLN stations (2, 3, 4, 7, 10, and 11). We report our initial experience with this procedure. METHODS Using our prospectively maintained database, we performed a single-institution retrospective chart review. Our study group consisted of all patients at the University of Minnesota who underwent EBUS-FNA for evaluation of mediastinal lymphadenopathy or for thoracic malignancy staging from September 1, 2006, through December 15, 2007. To assess our learning curve, we plotted the cumulative sensitivity (%) and accuracy (%) of our EBUS-FNA results as a function of the number of procedures we performed. RESULTS During the study period, 100 patients underwent EBUS, 92 with FNA. Of these, 56 patients (34 women, 22 men; mean age, 60.4 +/- 13.7 years) met our inclusion criteria. We found no complications. After our first 10 procedures, the sensitivity of our EBUS-FNA results was 96.2%; accuracy was 97.8% (rates comparable with other large series in the literature). CONCLUSIONS We conclude that the learning curve for EBUS-FNA for thoracic surgeons is about 10 procedures.

Thoracoscopic Versus Thoracotomy Approaches to Lobectomy: Differential Impairment of Cellular Immunity

BACKGROUND Video-assisted thoracoscopic surgery (VATS) for patients with early-stage non-small-cell lung cancer is associated with lower stress responses and potentially improved outcomes, as compared with thoracotomy. The goal of our study was to examine the cellular components of the postoperative immune response. Specifically, we assessed the cytotoxic capacity of peripheral blood mononuclear cells (PBMCs) of patients undergoing lobectomy for non-small-cell lung cancer by either VATS or thoracotomy. METHODS We performed a prospective cohort study of lobectomy patients undergoing either VATS or thoracotomy. We isolated PBMCs from perioperative blood samples, and performed cytokine analysis on plasma fractions. Using flow cytometry, we analyzed PBMC phenotype (CD3, CD16/56, CD4, CD8) and T-cell activation markers (CD25, CD69, HLA-DR). Using a chromium release assay, we quantified cellular cytotoxicity. To assess gene expression differences, we used Affymetrix messenger ribonucleic acid microarray and polymerase chain reaction analysis. RESULTS A total of 13 patients enrolled in our study: 6, VATS; 7, thoracotomy. On postoperative day 1, interleukin-6 and matrix metalloproteinase-9 were significantly different between the two groups. On day 2, cellular cytotoxicity (0.34) was significantly greater (p < 0.05) after VATS, as compared with thoracotomy (0.18). In both groups, cytotoxicity returned to baseline and was equivalent at first follow-up (VATS, 29.4 days versus thoracotomy, 29.3 days; p > 0.05). We noted minimal yet significant differences in PBMC phenotype, but no differences in T-cell activation makers. A 9-gene polymerase chain reaction-validated subset clustered the two groups with complete concordance. CONCLUSIONS Video-assisted thoracoscopic surgery lobectomy for non-small-cell lung cancer is associated with less impairment of cellular cytotoxicity, as compared with thoracotomy. We found that this difference was not accounted for by PBMC phenotypic changes. Instead, PBMC gene expression changes likely represent the molecular basis of this differential immune response.

Determination of the minimum number of lymph nodes to examine to maximize survival in patients with esophageal carcinoma: data from the Surveillance Epidemiology and End Results database.

OBJECTIVE We used a population-based cancer registry to examine the association between lymph node counts and mortality to determine the minimum number of lymph nodes that should be examined as part of esophageal resection. METHODS Using the Surveillance Epidemiology and End Results database, we identified patients who had an esophagectomy for invasive esophageal carcinoma from 1988 through 2005 and who had a known number of lymph nodes examined pathologically. After stratifying patients (0, 1-11, 12-29, and 30 or more lymph nodes examined) based on a recursive partitioning analysis, we assessed the association between lymph nodes counts and mortality using the Kaplan-Meier method. To adjust for potential confounding covariates, we used a Cox proportional hazards regression model. RESULTS Of the patients in the Surveillance Epidemiology and End Results database with esophageal cancer, 4882 met our inclusion criteria. We noted a significant difference between the lymph node groups with regards to unadjusted all-cause (P < .0001) and cancer-specific mortality (P = .004). After adjusting for cancer registry, patient factors, tumor characteristics, and timing of radiation therapy, we noted a significant difference between the lymph node groups with regards to all-cause and cancer-specific mortality. Compared with patients who had no lymph node evaluation, only patients who had more than 12 lymph nodes examined had a significant improvement in mortality; patients who had 30 or more lymph nodes examined had significantly lower mortality rates than the other groups. CONCLUSION To maximize all-cause and cancer-specific survival, esophageal cancer patients should have at least 30 lymph nodes examined pathologically as part of esophageal resection.

Risk of Adverse Outcomes Associated With Blood Transfusion After Cardiac Surgery Depends on the Amount of Transfusion

BACKGROUND Blood product transfusion has been known for immunosuppressive effects, and over-transfusion is linked with adverse outcomes. In cardiac surgery, the risk of non-transfusion can be poor postoperative oxygen delivery and hemorrhage. We hypothesized that infectious complications, organ dysfunction, and mortality result after a given threshold of blood product transfusion is exceeded. METHODS Retrospectively, a prospectively maintained institutional database was analyzed from April 1, 2004 through December 31, 2006. All patients undergoing coronary artery bypass and/or valve operations were evaluated for bivariate and multivariate associations of blood-product transfusion with postoperative complications and mortality. Additionally, risk factors associated with transfusion were assessed. Receiver operator characteristic (ROC) curves analyses were employed to determine transfusion thresholds associated with complications. RESULTS During the study period, 741 patients met inclusion criteria. Fifty-four percent received postoperative blood-product transfusions. Previous cardiac intervention, renal dysfunction, stroke, and immunosuppression were some of the risks associated with transfusion (P < 0.05). Specific complications independently (P < 0.05) associated with total blood product transfusion identified from the multivariate analysis were infectious, neurologic, organ dysfunction, cardiac, and death. From ROC curve analyses, 5.5 units of total blood product transfusion was the inflection point for infectious complications (sensitivity 73%, specificity 64%) and organ dysfunction (sensitivity 73%, specificity 64%). For mortality, the inflection point was a transfusion of 7.5 units of total blood-products (sensitivity 73%, specificity 71%). CONCLUSION Bloodless cardiac surgery is associated with a decreased morbidity and mortality. Limiting transfusion is advisable. Transfusion of less than 5.5 units of total blood-products may not have deleterious effects on outcomes.

Repression of Cap-Dependent Translation Attenuates the Transformed Phenotype in Non-Small Cell Lung Cancer Both In vitro and In vivo

Aberrant hyperactivation of the cap-dependent protein synthesis apparatus has been documented in a wide range of solid tumors, including epithelial carcinomas, but causal linkage has only been established in breast carcinoma. In this report, we sought to determine if targeted disruption of deregulated cap-dependent translation abrogates tumorigenicity and enhances cell death in non-small cell lung cancer (NSCLC). NSCLC cell lines were stably transfected with either wild-type 4E-BP1 (HA-4E-BP1) or the dominant-active mutant 4E-BP1(A37/A46) (HA-TTAA). Transfected NSCLC cells with enhanced translational repression showed pronounced cell death following treatment with gemcitabine. In addition, transfected HA-TTAA and HA-4E-BP1wt proteins suppressed growth in a cloning efficiency assay. NSCLC cells transduced with HA-TTAA also show decreased tumorigenicity in xenograft models. Xenograft tumors expressing HA-TTAA were significantly smaller than control tumors. This work shows that hyperactivation of the translational machinery is necessary for maintenance of the malignant phenotype in NSCLC, identifies the molecular strategy used to activate translation, and supports the development of lung cancer therapies that directly target the cap-dependent translation initiation complex.

Multilaminate resorbable biomedical device under biaxial loading

The design and test of a multilaminate sheet developed for a hernia repair application is presented. As biomaterial applications become more complex, characterization of uniaxial properties becomes insufficient and biaxial testing becomes necessary. A measure of the in-plane biaxial strength of the device is inferred from a ball burst test. The results of this test for different thicknesses of the device are correlated with the uniaxial strength of the material. A biaxial test such as the ball burst test is more indicative of the properties of a planar material than would be a uniaxial test. The interactions in the biaxial mode of failure are of value and can be related back to a classical uniaxial tensile test from the ball burst test. The material used in this study to fabricate the device was a resorbable biomaterial called small intestinal submucosa (SIS). The effects of rehydration on the stiffness and associated ball burst properties of the SIS device were also measured. It is shown that at a rehydration time of 5 min from a reference dry state, steady-state mechanical properties are reached.

Primary Palmoplantar Hyperhidrosis and Thoracoscopic Sympathectomy: A New Objective Assessment Method

BACKGROUND This study was conducted to establish an objective approach to evaluate symptoms and sweat production in patients with primary palmoplantar hyperhidrosis (PPH) and assess their response to bilateral thoracoscopic sympathectomy (BTS). METHODS We conducted two institutional review board-approved studies. We performed a one-time evaluation of healthy volunteers (controls) with three questionnaires (Hyperhidrosis Disease Severity Scale, Dermatology Life Quality Index, and Short Form-36) and measurement of transepidermal water loss (TEWL; g/m(2)/h). We evaluated PPH patients with these same tools before and 1 month after BTS and compared them with controls. RESULTS We evaluated 35 controls (mean age, 23.0 +/- 3.3 years) and 45 PPH patients (mean age, 26.5 +/- 12.3 years); 18 PPH patients underwent BTS and the 1-month postoperative evaluation. Hyperhidrosis Disease Severity Scale and Dermatology Life Quality Index scores were higher in PPH patients than in controls (p < 0.0001), but normalized after BTS. Short Form-36 scale scores were lower in PPH patients than in controls (p < 0.05), but improved significantly after BTS. Compared with controls, preoperative TEWL values were significantly higher in PPH patients (palmar: 142.7 +/- 43.6 PPH vs 115.8 +/- 48.7 controls, p = 0.011; plantar: 87.5 +/- 28.8 PPH vs 57.7 +/- 24.7 controls, p < 0.0001). After BTS, palmar TEWL values were significantly lower (49.1 +/- 29.8, p < 0.0001). Plantar TEWL did not change significantly (77.6 +/- 46.6, p = 0.52). CONCLUSIONS PPH patients should be objectively evaluated with standardized quality of life measures and TEWL measurements before and after treatment. We believe that this objective practical approach provides a benchmark for clinical practice and research.

Impact of preoperative smoking status on postoperative complication rates and pulmonary function test results 1-year following pulmonary resection for non-small cell lung cancer

There is a lack of evidence in the literature regarding the impact of preoperative smoking status on pulmonary function test (PFT) results 1 year after resection for non-small cell lung cancer (NSCLC). Furthermore, there is disagreement in the literature regarding the impact of preoperative smoking cessation on postoperative complication rates. We performed a single-institution retrospective review of all NSCLC patients who underwent resection from April 2000 through April 2006. Timing of smoking cessation was stratified as follows: smoking cessation more than a month before surgery (Distant Smokers), smoking cessation within a month before surgery (Recent Smokers), and failure to achieve smoking cessation before surgery (Current Smokers). During the study period, 213 patients underwent NSCLC resection, 121 of whom (all males; mean age, 67.4 years) completed pre- and postoperative PFTs. After adjusting for potential confounding covariates (age, type of resection, and use of radiation therapy), we noted no significant difference (p>0.40) between groups after resection with regard to either relative (-12.20+/-15.77L [Distant Smokers], -15.38+/-19.38L [Recent Smokers], -9.61+/-15.54L [Current Smokers]) or absolute changes in percent predicted forced expiratory volume in 1s (-0.14+/-0.20L [Distant Smokers], -0.18+/-0.19L [Recent Smokers], -0.12+/-0.20L [Current Smokers]). Because 92 patients did not complete postoperative PFTs, we performed a stratified analysis to assess for selection bias; as compared with those who completed PFTs, baseline PFT results did not significantly differ. We found no significant differences between the 3 groups with regard the overall rate of postoperative complications or the rate of any specific postoperative complication. In conclusion, smoking cessation immediately before NSCLC resection does not significantly impact postoperative pulmonary complication rates or 1-year postoperative PFT results and therefore should not be a reason to delay surgical resection.