Lobectomy offers improved survival outcomes relative to segmentectomy for >2 but ≤4 cm non-small cell lung cancer tumors.

Objective: The objective was to compare overall survival (OS) between lobectomy and segmentectomy for patients with non-small cell lung cancers (NSCLCs) > 2 but ≤4 cm. Methods: The National Cancer Database was queried to identify treatment-naïve patients with NSCLC tumors >2 but ≤4 cm. Eligible patients were diagnosed with pT1 or T2 N0 M0 disease, underwent lobectomy or segmentectomy, and received no adjuvant therapy. OS was compared using the Kaplan-Meier method, and the Cox proportional-hazards model was used to identify prognostic factors for death. Propensity score matching was performed to minimize the effects of potential confounders. Results: Included were 32,792 patients: lobectomy (n = 31,353) and segmentectomy (n = 1439). Five-year OS was improved following lobectomy over segmentectomy for patients with >2 but ≤4 cm NSCLCs (62.3% vs 52.6%; P < .0001). Further stratification demonstrated improved 5-year OS following lobectomy over segmentectomy: >2 but ≤3 cm (64.9% vs 54.3%; P < .0001) and >3 but ≤4 cm (56.9% vs 47.6%; P = .0003). In patients with a Charlson-Deyo comorbidity index of 0, 5-year OS was greater following lobectomy for >2 but ≤4 cm tumors (67.1% vs 62.1%; P = .03). Further stratification demonstrated improved 5-year OS following lobectomy for patients with Charlson-Deyo comorbidity index of 0 and > 3 but ≤4 cm tumors (61.8% vs 54.6%; P = .02). Segmentectomy was prognostic for increased risk of death in the year 1 through 5 postoperative period (hazard ratio, 1.35; P < .0001). Five-year OS remained greater following lobectomy after propensity score matching (59.6% vs 52.7%; P = .02). Conclusions: Lobectomy is associated with superior 5-year OS compared with segmentectomy and may be preferred for NSCLC tumors >2 but ≤4 cm when feasible.

Enhanced Recovery After Surgery Protocol Minimizes Intensive Care Unit Utilization and Improves Outcomes Following Pulmonary Resection.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been associated with improved postoperative outcomes but require further validation in thoracic surgery. This study evaluated outcomes of patients undergoing pulmonary resection before and after implementation of an ERAS protocol. METHODS: Electronic medical records were queried for all patients undergoing pulmonary resection between April 2017 and April 2019. Patients were grouped into pre- and post-ERAS cohorts based on dates of operation. The ERAS protocol prioritized early mobilization, limited invasive monitoring, euvolemia, and non-narcotic analgesia. Primary outcome measures included intensive care unit (ICU) utilization, postoperative pain metrics, and perioperative morbidity. Regression analyses were performed to identify predictors of morbidity. Subgroup analyses were performed by pulmonary risk profile and surgical approach. RESULTS: A total of 64 pre- and 67 post-ERAS patients were included in the study. ERAS implementation was associated with reduced postoperative ICU admission (pre: 65.6% vs. post: 19.4%, p < 0.0001), shorter ICU median length of stay (LOS) (pre: 1 vs. post: 0, p < 0.0001), and decreased opioid usage measured by median morphine milligram equivalents (pre: 40.5 vs. post: 20.0, p < 0.0001). Post-ERAS patients also reported lower visual analog scale (VAS) pain scores on postoperative days (POD) 1 and 2 (pre: 6.3/5.6 vs. post: 5.3/4.2, p = 0.04/0.01) as well as average VAS pain score over POD0-2 (pre: 6.2 vs. post: 5.2, p = 0.005). CONCLUSIONS: Implementation of an ERAS protocol for pulmonary resection, which dictated reduced ICU admissions, did not increase major postoperative morbidity. Additionally, ERAS-enrolled patients reported improved postoperative pain control despite decreased opioid utilization.

Differential outcomes of residual disease in surgically-resected non-small cell lung cancer and the importance of guideline-concordant adjuvant therapy.

BACKGROUND: Positive mediastinal lymph nodes, a marker for systemic disease, and positive margins, a marker for local disease, following resection of non-small cell lung cancer (NSCLC) are forms of residual disease. The objective of this study is to compare survival of patients with residual disease and to study the effect of receipt of guideline vs. non-guideline concordant care. METHODS: The National Cancer Database (NCDB) was used to identify patients who underwent treatment naïve surgical resection with clinical stage T1-3N0-1M0 NSCLC between 2006-2016 and had pN2 disease, positive surgical margins, or both. Concordant care was determined based on form of chemotherapy and radiation, dosage, volume, modality, and duration. Kaplan-Meier survival curves and log-rank tests were used to compare five-year survival. Multivariable analysis using Cox proportional hazards modeling identified factors that contributed to worse overall survival. RESULTS: There were 8,189 patients included: pN2 (5,416), positive margins (2,386), and both (387). Five-year survival rates for all patients were pN2 (35.8%), positive margins (33.9%), and both (22.9%) (P<0.0001). On multivariable analysis, positive margins were an independent predictor of better survival relative to pN2 disease (HR =0.729, CI: 0.676, 0.787, P<0.0001). Receipt of non-guideline concordant treatment was an independent predictor of worse survival compared to receipt of guideline-concordant treatment (HR =1.61, CI: 1.504, 1.725, P<0.0001). CONCLUSIONS: In upfront surgical patients, guideline-concordant treatment in the setting of residual disease is associated with better overall survival compared with non-guideline concordant treatment. Pathologic N2 disease is associated with a lower survival rate than positive resection margins, possibly reflecting the systemic nature of pN2 disease.

Understanding thoracic surgeons' perceptions of administrative database analyses and guidelines in clinical decision-making.

OBJECTIVES: This study explored cardiothoracic surgeons' perceptions of health services research and practice guidelines, particularly how both influence providers' clinical decision-making. METHODS: A trained interviewer conducted open-ended, semistructured phone interviews with cardiothoracic surgeons across the United States. The interviews explored surgeons' experiences with lung cancer treatment and their perceptions of health services research and guidelines. Researchers coded the transcribed interviews using conventional content analysis. Interviews continued until thematic saturation was reached. RESULTS: The 27 surgeons interviewed mostly were general thoracic surgeons (23/27) who attend tumor board weekly (21/27). Five themes relating to physician perceptions of health services research and guidelines emerged. Databases analyses' inherent selection bias and perceived deficit of pertinent clinical variables made providers skeptical of using these studies as primary decision drivers; however, providers thought that database analyses are useful to supplement other data and drive future research. Likewise, providers generally felt that although guidelines provide a useful framework, they often have difficulty applying guidelines to individual patients. An analysis of provider characteristics revealed that younger physicians in practice for fewer years appeared more likely to report using guidelines, and physicians who were aged 50 years or more and not purely academic surgeons appeared to find database analyses less impactful. CONCLUSIONS: Health services research, including database analyses, comprise much of the surgical literature; however, this study suggests that perceptions of database analyses and guidelines are mixed and questions whether thoracic surgeons routinely use either to inform their decisions. Researchers must address how to present compelling data to influence clinical practice.

Ethanol differentially modulates P2X4 and P2X7 receptor activity and function in BV2 microglial cells.

Neuroinflammation is one of the mechanisms leading to neurodegenerative brain damage induced by chronic alcohol (ethanol) exposure. Microglia play a major role in the development of innate immune responses to environmental injuries including ethanol. Adenosine 5″-triphosphate (ATP)-activated purinergic P2X receptor (P2XR) subtypes, P2X4Rs and P2X7Rs, are endogenously expressed in microglia and can modulate their activity. These 2 P2XR subtypes differ pharmacologically and functionally: 1) P2X4Rs are activated at lower (≤0.1 mM) whereas P2X7Rs - at higher (≥1.0 mM) ATP concentrations; 2) P2X4R activation contributes to the release of brain derived neurotrophic factor and its role in tactile allodynia and neuropathic pain is demonstrated; 3) Due to its role in the secretion of pro-inflammatory IL-1ß, P2X7Rs have been implicated in the development of neurodegenerative pathologies, pain and morphine tolerance. To date, the roles of individual P2XR subtypes in ethanol effects on microglia and the functional consequences are not completely understood. Based on the existing knowledge on the pharmacological and functional differences between P2X4Rs and P2X7Rs, the present work tested the hypothesis that P2X4Rs and P2X7Rs play differential roles in ethanol action in microglia. Effects of ethanol on P2X4R and P2X7R activity, expression and functional consequences were determined using murine BV2 microglial cells. Ethanol (≥100 mM) inhibited P2X4Rs but was inactive on P2X7 channel activity. Ethanol (25, 100 mM) inhibited P2X4R-mediated microglia migration whereas it potentiated pore formation in P2X7Rs. Furthermore, ethanol (25, 100 mM) potentiated P2X7R-mediated IL-1ß secretion from BV2 microglia. Ethanol also induced protein expression for both P2XR subtypes. Overall, the findings identify differential roles for P2X4Rs and P2X7Rs in regards to ethanol effects on microglia which may be linked to different stages of ethanol exposure.

Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals.

Prior to testing novel therapeutics in humans, short and long term preclinical (i.e., animal), repetitive pharmacological and toxicological testing is required. In most cases, the preferred route of administration is via oral delivery. At the present time, oral delivery is mostly accomplished using an oral gavage procedure, in part, because it can achieve consistent and precise dosing in the animal model. Although this method is well established it does have complications that can result in a high rate of animal attrition. To this end, the procedure introduced here describes an alternative to the oral gavage method in which the desired drug is incorporated into a tastant, orally dissolving strip (ODS) that can simply be presented to the test animal where it is then rapidly taken up with minimal manipulation of the test subject. Herein, we demonstrate that preclinical, oral drug delivery using the ODS method represents a safe, convenient, and humane alternative to oral gavage.