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The effects of minimally invasive and open surgical approaches on immune effector cell function and the implications for early-stage non-small-cell lung cancer

Posted on:2008-07-12Degree:Ph.DType:Thesis
University:University of MinnesotaCandidate:Whitson, Bryan AlanFull Text:PDF
GTID:2444390005473320Subject:Biology
Abstract/Summary:
Advances in optics, instrumentation, and anesthesia are enabling more operations to be performed through minimally invasive (MIS) approaches. When procedures are amenable to MIS approaches, compared to the traditional open approaches, patients are spared large morbid incisions and prolonged convalescence. Data are beginning to suggest that MIS approaches have superior clinical outcomes. In oncologic settings, specifically non-small cell lung cancer (NSCLC), there may be improved cancer related outcomes. These outcome differences may be mediated by immune effector cell function.; The hypotheses tested are that in the setting of lobectomy for treatment of NSCLC (1) the MIS approach is associated with improved clinical outcomes as compared with the open approach; and (2) the MIS approach has a less detrimental effect on immune effector cell function as compared with the open approach. Hypothesis 1 was evaluated through a clinical outcome analysis of patients undergoing lobectomy for NSCLC at the University of Minnesota Medical Center and a systematic review of the relevant published world's literature. Hypothesis 2 was evaluated through both non-oncologic (Roux-en-Y gastric bypass) and oncologic (lobectomy for NSCLC) basic science models. The non-oncologic model attempted to remove clinical confounders. While the oncologic model evaluated the effect of surgical stress in the same patient population as was included in the clinical outcome analyses (hypothesis 1).; The MIS approaches to surgery demonstrated less perioperative immunosuppression than did the traditional open approaches. This phenomenon was reproducible in both non-oncologic (Roux-en-Y gastric bypass) and oncologic (lobectomy for early-stage NSCLC) settings. The MIS approach to lobectomy for early-stage NSCLC demonstrated superior outcomes, as compared to the thoracotomy approach: less morbidity (i.e., fewer overall complications, pneumonias, shorter length of hospital stay, and fewer number of chest tube days) and improved overall survival. Differential gene expression changes in immune effector cells, attributable to the influences of surgical approach, may represent the underlying mechanisms for these observed functional and clinical outcome differences. These investigations serve as the basis for future investigations into tailoring surgical therapy to individual patients and disease processes as well as immunomodulative adjuncts to surgical treatment of both non-oncologic and oncologic diseases.
Keywords/Search Tags:Immune effector cell function, Approach, Surgical, MIS, Open, Both non-oncologic, NSCLC, Early-stage
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