title: Thoracoscopic versus thoracotomy approaches to lobectomy: differential impairment of cellular immunity.
abstract: 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.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Whitson
authors.forename: Jonathan
authors.initials: J
authors.lastname: D'Cunha
authors.forename: Rafael S
authors.initials: RS
authors.lastname: Andrade
authors.forename: Rosemary F
authors.initials: RF
authors.lastname: Kelly
authors.forename: Shawn S
authors.initials: SS
authors.lastname: Groth
authors.forename: Baolin
authors.initials: B
authors.lastname: Wu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
authors.forename: Michael A
authors.initials: MA
authors.lastname: Maddaus
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000379:methods / Q000401:mortality; D011182:Postoperative Care / Q000379:methods; D011183:Postoperative Complications / Q000453:epidemiology / Q000276:immunology; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D020775:Thoracic Surgery, Video-Assisted / Q000379:methods* / Q000401:mortality; D013908:Thoracotomy / Q000379:methods* / Q000401:mortality
chemical_list: D015415:Biomarkers; D016207:Cytokines