Lung and blood perioperative metalloproteinases in patients undergoing oncologic lung surgery: Prognostic implications.

BACKGROUND: Metalloproteinases (MMPs) have been reported to be related to oncologic outcomes. The main goal of the study was to study the relationship between these proteins and the long-term prognosis of patients undergoing oncologic lung resection surgery. METHODS: This was a substudy of the phase IV randomized control trial (NCT02168751). We analyzed MMP-2, -3, -7, and -9 in blood samples and bronchoalveolar lavage (LBA) and the relationship between MMPs and long postoperative outcomes (survival and disease-free time of oncologic recurrence). RESULTS: Survival was longer in patients who had lower MMP-2 levels than those with higher MMP-2 in blood samples taken 6 h after surgery (6.8 vs. 5.22 years; p = 0.012) and MMP-3 (6.82 vs. 5.35 years; p = 0.03). In contrast, survival was longer when MMP-3 levels were higher in LBA from oncologic lung patients than those with lower MMP-3 (7.96 vs. 6.02 years; p = 0.005). Recurrence-free time was longer in patients who had lower MMP-3 levels in blood samples versus higher (5.97 vs. 4.23 years; p = 0.034) as well as lower MMP-7 (5.96 vs. 4.5 years; p = 0.041) or lower MMP-9 in LBA samples (6.21 vs. 4.18 years; p = 0.012). CONCLUSION: MMPs were monitored during the perioperative period of oncologic lung resection surgery. These biomarkers were associated with mortality and recurrence-free time. The role of the different MMPs analyzed during the study do not have the same prognostic implications after this kind of surgery.

Influence of postoperative complications on long-term outcome after oncologic lung resection surgery. Substudy of a randomized control trial.

Lung resection surgery (LRS) causes an intense local and systemic inflammatory response. There is a relationship between inflammation and postoperative complications (POCs). Also, it has been proposed that the inflammation and complications related with the surgery may promote the recurrence of cancer and therefore deterioration of survival. We investigated the association between inflammatory biomarkers, severity of POCs and long-term outcome in patients who were discharged after LRS. This is a prospective substudy of a randomized control trial. We established three groups based in the presence of POCs evaluated by Clavien-Dindo (C-D) classification: Patients with no postoperative complications (No-POCs group) (C-D = 0), patients who developed light POCs (L-POCs group) (C-D = I-II), and major POCs (M-POCs group) (C-D = III, IV, or V). Kaplan-Meier curves and Cox regression model were created to compare survival and oncologic recurrence in those groups. Patients who developed POCs (light or major) had an increase in some inflammatory biomarkers (TNF-α, IL-6, IL-7, IL-8) compared with No-POCs group. This pro-inflammatory status plays a fundamental role in the appearance of POCs and therefore in a shorter life expectancy. Individuals in the M-POCs group had a higher risk of death (HR = 3.59, 95% CI 1.69 to 7.63) compared to individuals in the No-POCs group (p = 0.001). Patients of L-POCs group showed better survival than M-POCs group (HR = 2.16, 95% CI 1.00 to 4.65, p = 0.049). Besides, M-POCs patients had higher risk of recurrence in the first 2 years, when compared with L-POCs (p = 0,008) or with No-POCs (p = 0.002). In patients who are discharged after undergoing oncologic LRS, there is an association between POCs occurrence and long term outcome. Oncologist should pay special attention in patients who develop POCs after LRS.

Effect of intraoperative paravertebral or intravenous lidocaine versus control during lung resection surgery on postoperative complications: A randomized controlled trial.

BACKGROUND: Use of minimally invasive surgical techniques for lung resection surgery (LRS), such as video-assisted thoracoscopy (VATS), has increased in recent years. However, there is little information about the best anesthetic technique in this context. This surgical approach is associated with a lower intensity of postoperative pain, and its use has been proposed in programs for enhanced recovery after surgery (ERAS). This study compares the severity of postoperative complications in patients undergoing LRS who have received lidocaine intraoperatively either intravenously or via paravertebral administration versus saline. METHODS/DESIGN: We will conduct a single-center randomized controlled trial involving 153 patients undergoing LRS through a thoracoscopic approach. The patients will be randomly assigned to one of the following study groups: intravenous lidocaine with more paravertebral thoracic (PVT) saline, PVT lidocaine with more intravenous saline, or intravenous remifentanil with more PVT saline. The primary outcome will be the comparison of the postoperative course through Clavien-Dindo classification. Furthermore, we will compare the perioperative pulmonary and systemic inflammatory response by monitoring biomarkers in the bronchoalveolar lavage fluid and blood, as well as postoperative analgesic consumption between the three groups of patients. We will use an ANOVA to compare quantitative variables and a chi-squared test to compare qualitative variables. DISCUSSION: The development of less invasive surgical techniques means that anesthesiologists must adapt their perioperative management protocols and look for anesthetic techniques that provide good analgesic quality and allow rapid rehabilitation of the patient, as proposed in the ERAS protocols. The administration of a continuous infusion of intravenous lidocaine has proven to be useful and safe for the management of other types of surgery, as demonstrated in colorectal cancer. We want to know whether the continuous administration of lidocaine by a paravertebral route can be substituted with the intravenous administration of this local anesthetic in a safe and effective way while avoiding the risks inherent in the use of regional anesthetic techniques. In this way, this technique could be used in a safe and effective way in ERAS programs for pulmonary resection. TRIAL REGISTRATION: EudraCT, 2016-004271-52; ClinicalTrials.gov, NCT03905837 . Protocol number IGGFGG-2016 version 4.0, 27th April 2017.

Usefulness of combining clinical and biochemical parameters for prediction of postoperative pulmonary complications after lung resection surgery.

Early detection of patients with a high risk of postoperative pulmonary complications (PPCs) could improve postoperative strategies. We investigated the role of monitoring systemic and lung inflammatory biomarkers during surgery and the early postoperative period to detect patients at high risk of PPCs after lung resection surgery (LRS). This is a substudy of a randomized control trial on the inflammatory effects of anaesthetic drugs during LRS. We classified patients into two groups, depending on whether or not they developed PPCs. We constructed three multivariate logistic regression models to analyse the power of the biomarkers to predict PPCs. Model 1 only included the usual clinical variables; Model 2 included lung and systemic inflammatory biomarkers; and Model 3 combined Models 1 and 2. Comparisons between mathematical models were based on the area under the receiver operating characteristic curve (AUROC) and tests of integrated discrimination improvement (IDI). Statistical significance was set at p < 0.05. PPCs were detected in 37 (21.3%) patients during admission. The AUROC for Models 1, 2, and 3 was 0.79 (95% CI 0.71-0.87), 0.80 (95% CI 0.72-0.88), and 0.93 (95% CI 0.88-0.97), respectively. Comparison of the AUROC between Models 1 and 2 did not reveal statistically significant values (p = 0.79). However, Model 3 was superior to Model 1 (p < 0.001). Model 3 had had an IDI of 0.29 (p < 0.001) and a net reclassification index of 0.28 (p = 0.007). A mathematical model combining inflammation biomarkers with clinical variables predicts PPCs after LRS better than a model that includes only clinical data. Clinical registration number Clinical Trial Registration NCT02168751; EudraCT 2011-002294-29.

Systemic and alveolar inflammatory response in the dependent and nondependent lung in patients undergoing lung resection surgery: A prospective observational study.

BACKGROUND: Measurement of inflammatory mediators in bronchoalveolar lavage (BAL) during lung resection surgery with periods of one-lung ventilation (OLV) has revealed an intense local pulmonary response. The role of each lung in the inflammation that occurs during this procedure has never been investigated. OBJECTIVE(S): The primary objective of our study was to compare the inflammatory response in the dependent lung with that of the nondependent lung by measuring inflammatory markers in BAL. Our secondary objective was to assess the behaviour of these inflammatory mediators in patients with and without postoperative pulmonary complications (PPCs). DESIGN: A prospective, observational study. SETTING: Department of Anaesthesiology in a university hospital. PATIENTS: Forty-six consecutive patients undergoing lung resection surgery. INTERVENTION(S): BAL samples were taken from dependent and nondependent lung 10 min before initiating OLV and at the end of OLV (once two-lung ventilation was established). All patients were followed up until 30 days after surgery. MAIN OUTCOME MEASURES: The concentration of cytokines [interleukin (IL)-1, IL-2, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α)], nitric oxide, carbon monoxide and matrix metalloproteinase 2 (MMP-2) was analysed in both lungs before and after OLV. PPCs were recorded. RESULTS: In BAL fluid, all measured biomarkers, apart from IL-10, were significantly greater (P < 0.05) at the end of OLV than those obtained before OLV, both for the dependent and nondependent lung. The increase in measured biomarkers was similar in both lungs. Eight patients developed PPC. Patients who developed PPC had higher levels of TNF-α (P < 0.05) in BAL from the nondependent lung before and after OLV than patients who did not have PPC. Patients who developed PPC had a smaller increase in MMP-2 levels (P < 0.05) in the dependent lung than patients who did not have PPC. CONCLUSION: In lung resection surgery, the inflammatory response is similar in both lungs. However, the greater increase in TNF-α levels in the nondependent lung and the smaller increase of MMP-2 concentration in the dependent lung may increase the susceptibility to develop PPC.