Philip W. Carrott

Lung ischemia-reperfusion injury (IRI), characterized by inflammation, vascular permeability, and lung edema, is the major cause of primary graft dysfunction after lung transplantation. Here, we investigated the cellular mechanisms underlying lung IR–induced activation of endothelial TRPV4 channels, which play a central role in lung edema and dysfunction after IR. In a left lung hilar-ligation model of IRI in mice, we found that lung IRI increased the efflux of ATP through pannexin 1 (Panx1) channels at the endothelial cell (EC) membrane. Elevated extracellular ATP activated Ca ²⁺ influx through endothelial TRPV4 channels downstream of purinergic P2Y2 receptor (P2Y2R) signaling. P2Y2R-dependent activation of TRPV4 channels was also observed in human and mouse pulmonary microvascular endothelium in ex vivo and in vitro models of IR. Endothelium-specific deletion of P2Y2R, TRPV4, or Panx1 in mice substantially prevented lung IRI–induced activation of endothelial TRPV4 channels and lung edema, inflammation, and dysfunction. These results identify endothelial P2Y2R as a mediator of the pathological sequelae of IRI in the lung and show that disruption of the endothelial Panx1-P2Y2R-TRPV4 signaling pathway could be a promising therapeutic strategy for preventing lung IRI after transplantation.

Video-assisted thoracic surgery (VATS) lobectomy has become the standard of care for early stage lung cancer throughout the world. Teaching this complex procedure requires adequate case volume, adequate instrumentation, a committed operating room team and baseline experience with open lobectomy. We outline what key maneuvers and steps are required to teach and learn VATS lobectomy. This is most easily performed as part of a thoracic surgery training program, but with adequate commitment and proctoring, there is no reason experienced open surgeons cannot become proficient VATS surgeons. We provide videos showing the key portions of a subcarinal lymph node dissection, posterior hilar dissection of the right upper lobe, fissureless right middle lobectomy, and fissureless left lower lobectomy. These videos highlight what we feel are important principals in VATS lobectomy, i.e., N2 and N1 lymph node dissection, fissureless techniques, and progressive responsibility of the learner. Current literature in simulation of VATS lobectomy is also outlined as this will be the future of teaching in VATS lobectomy.

The ability to assess and compare the impact of postoperative complications in major cancer surgery is currently limited. The Accordion Severity Grading System provides the opportunity to categorize complications according to treatment responses and resource use. A retrospective review of patient demographics, perioperative outcomes, and costs was performed using a prospective IRB-approved database of patients undergoing esophagectomy from 2000 to 2008. This study included 285 consecutive patients, 83% were male, and mean age was 63.7 years. Histology was predominantly adenocarcinoma (80%). For patients with invasive cancer, overall survival at 5 years was 50%. Mean overall cost and length of stay were $23,419 and 10.4 days, respectively. Neoadjuvant therapy was used in 156 patients (54.7%) and operative mortality rate was 0.7%. Complications were documented in 144 patients (50.5%), with Accordion grades assigned as 1 (29%), 2 (59%), 3 (3%), 4 (6%), 5 (2%), and 6 (0.7%). Accordion grade was significantly related to costs and length of stay in univariate (p < 0.005) and multivariate analyses (p < 0.005). There was a statistically significant difference in survival between those patients who did and did not experience complications; however, no significant differences were noted among individual Accordion grades. Cox regression multivariate analysis demonstrated a significant relationship between overall survival and occurrence of postoperative complications. The Accordion Severity Grading System provides a meaningful approach to classifying complications according to resource use, which also directly correlates with treatment costs and length of stay. Survival is affected by overall occurrence of complications, but was not related to individual Accordion grades in this study. The Accordion Severity Grading System should be a component of prospective data collections and can be used in major cancer surgery to study areas appropriate for quality improvement and cost containment.