Medico-economic impact of thoracoscopy versus thoracotomy in lung cancer: multicentre randomised controlled trial (Lungsco01).

BACKGROUND: Lungsco01 is the first study assessing the real benefits and the medico-economic impact of video-thoracoscopy versus open thoracotomy for non-small cell lung cancer in the French context. METHODS: Two hundred and fifty nine adult patients from 10 French centres were randomised in this prospective multicentre randomised controlled trial, between July 29, 2016, and November 24, 2020. Survival from surgical intervention to day 30 and later was compared with the log-rank test. Total quality-adjusted-life-years (QALYs) were calculated using the EQ-5D-3L®. For medico-economic analyses at 30 days and at 3 months after surgery, resources consumed were valorised (€ 2018) from a hospital perspective. First, since mortality was infrequent and not different between the two arms, cost-minimisation analyses were performed considering only the cost differential. Second, based on complete cases on QALYs, cost-utility analyses were performed taking into account cost and QALY differential. Acceptability curves and the 95% confidence intervals for the incremental ratios were then obtained using the non-parametric bootstrap method (10,000 replications). Sensitivity analyses were performed using multiple imputations with the chained equation method. RESULTS: The average cumulative costs of thoracotomy were lower than those of video-thoracoscopy at 30 days (€9,730 (SD = 3,597) vs. €11,290 (SD = 4,729)) and at 3 months (€9,863 (SD = 3,508) vs. €11,912 (SD = 5,159)). In the cost-utility analyses, the incremental cost-utility ratio was €19,162 per additional QALY gained at 30 days (€36,733 at 3 months). The acceptability curve revealed a 64% probability of efficiency at 30 days for video-thoracoscopy, at a widely-accepted willingness-to-pay threshold of €25,000 (34% at 3 months). Ratios increased after multiple imputations, implying a higher cost for video-thoracoscopy for an additional QALY gain (ratios: €26,015 at 30 days, €42,779 at 3 months). CONCLUSIONS: Given our results, the economic efficiency of video-thoracoscopy at 30 days remains fragile at a willingness-to-pay threshold of €25,000/QALY. The economic efficiency is not established beyond that time horizon. The acceptability curves given will allow decision-makers to judge the probability of efficiency of this technology at other willingness-to-pay thresholds. TRIAL REGISTRATION: NCT02502318.

Impact of video-assisted thoracic surgery approach on postoperative mortality after lobectomy in octogenarians.

OBJECTIVE: The number of octogenarians who present with localized lung cancer eligible for surgical resection is increasing. Video-assisted thoracic surgery lobectomy has been widely accepted, but the potential benefit in octogenarians is not well established, especially for postoperative mortality. This study aimed to assess the impact of a video-assisted thoracic surgery approach on postoperative mortality after lobectomy for lung cancer in octogenarians. METHODS: From January 2005 to December 2016, all patients aged more than 80 years who received lobectomy treatment for lung cancer were retrieved from the French Administrative Database. The end point was 30-day postoperative death. A propensity score was generated with 16 pretreatment variables and used to create balanced groups with matching (578 matches 1:1). Results are reported as odds ratios and 95% confidence intervals. RESULTS: Of the 75,892 patients operated for lobectomy during this period, 3560 were octogenarians. Video-assisted thoracic surgery was performed in 16.7% (n = 597) of cases, and thoracotomy was performed in 83.23% (n = 2963) of cases. From 2005 to 2016, the number of patients aged more than 80 years who were operated for lung cancer increased from 160 to 456 patients per year, and the proportion of lobectomy performed by video-assisted thoracic surgery increased as well (from 3.13% to 37.28%). Unmatched postoperative mortality was 3.85% (n = 23) for video-assisted thoracic surgery versus 7.9% (n = 234) for thoracotomy (P < .0001). Matched postoperative mortality was significantly lower in the video-assisted thoracic surgery approach with an odds ratio of 0.51 (95% confidence interval, 0.27-0.96; P = .038). CONCLUSIONS: Video-assisted thoracic surgery was significantly associated with reduced postoperative mortality compared with open thoracotomy after lobectomy for lung cancer in octogenarians.

Does age over 80 years have to be a contraindication for lung cancer surgery-a nationwide database study.

BACKGROUND: Nowadays surgery remains the best treatment for localized lung cancer (LC). However, patients over 80 years old are often denied surgery because of the postoperative risk of death. This study aimed to estimate in-hospital mortality (IHM) and determine whether age over 80 is the most important predictor of IHM after LC surgery. METHODS: From January 2005 to December 2015, 97,440 patients, including 4,438 patients over 80 years old, were operated on for LC and recorded in the French Administrative Database. Characteristics of patients, hospitals and surgery were analysed. RESULTS: Crude IHM was 3.73% (n=3,639) and 7.77% (n=345) for the over 80s vs. 3.54% (n=3,294) for younger patients (P<0.0001). In multivariate analysis, predictive factors for IHM with the odds ratios (OR) were: 2.60 for age ≥80 (95% CI: 2.30-2.94; P=0.0001), 5.85 for a previous liver disease (95% CI: 4.79-7.16; P=0.0001) and 5 for previous lung disease (95% CI: 4.25-5.9; P=0.0001). IHM was also linked to hospital volume with an OR of 0.75 (95% CI: 0.69-0.81; P=0.0001) and a linear decrease for predicted IHM according to hospital volume for the over 80s. Adjusted ORs were 1.15 (95% CI: 0.96-1.4; P=0.0116) for lobectomy, 2.18 for bilobectomy (95% CI: 1.7-2.8; P=0.0001) and 3.83 (95% CI: 3.2-4.6; P=0.0001) for pneumonectomy. CONCLUSIONS: Concerning IHM, age ≥80 had a lower weight than did a previous pulmonary or liver disease and the type of pulmonary resection. Patients over 80s with localized LC and no significant comorbidities should be referred for surgery if lobectomy or sublobar resection could be performed.

Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01).

INTRODUCTION: In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact. METHODS AND ANALYSIS: The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients. ETHICS AND DISSEMINATION: The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02502318.

Early postoperative prophylactic noninvasive ventilation after major lung resection in COPD patients: a randomized controlled trial.

OBJECTIVES: To investigate whether prophylactic postoperative NIV prevents respiratory complications following lung resection surgery in COPD patients. METHODS: In seven thoracic surgery departments, 360 COPD patients undergoing lung resection surgery were randomly assigned to two groups: conventional postoperative treatment without (n = 179) or with (n = 181) prophylactic NIV, applied intermittently during 6 h per day for 48 h following surgery. The primary endpoint was the rate of acute respiratory events (ARE) at 30 days postoperatively (ITT analysis). Secondary endpoints were acute respiratory failure (ARF), intubation rate, mortality rate, infectious and non-infectious complications, and duration of ICU and hospital stay. MEASUREMENTS AND MAIN RESULTS: ARE rates did not differ between the prophylactic NIV and control groups (57/181, 31.5 vs. 55/179, 30.7%, p = 0.93). ARF rate was 18.8% in the prophylactic NIV group and 24.5% in controls (p = 0.20). Re-intubation rates were similar in the prophylactic NIV and control group [10/181 (5.5%) and 13/179 (7.2%), respectively, p = 0.53]. Mortality rates were 5 and 2.2% in the control and prophylactic NIV groups, respectively (p = 0.16). Infectious and non-infectious complication rates, and duration of ICU and hospital stays were similar between groups. CONCLUSIONS: Prophylactic postoperative NIV did not reduce the rate of ARE in COPD patients undergoing lung resection surgery and did not influence other postoperative complications rates, mortality rates, and duration of ICU and hospital stay.

Comparison between systemic analgesia, continuous wound catheter analgesia and continuous thoracic paravertebral block: a randomised, controlled trial of postthoracotomy pain management.

CONTEXT: Thoracotomy is the surgical procedure that creates the greatest demand for postoperative analgesia. OBJECTIVE: We aimed to compare the efficacy of systemic analgesia, continuous wound catheter (CWC) analgesia and thoracic paravertebral block (TPVB) for pain management after thoracotomy, assessed by Visual Analogue Scale (VAS) pain score and morphine consumption. DESIGN: Prospective, randomised study. SETTING: University teaching hospital. Inclusions from April 2007 to February 2010. PATIENTS: 153 adult patients scheduled for pulmonary surgery. INTERVENTIONS: All three groups received systemic analgesia with paracetamol and morphine (patient-controlled analgesia, PCA). The PCA group received systemic analgesia only. The TPVB group underwent insertion of a paravertebral catheter and the CWC group underwent CWC catheter insertion at the end of the intervention. MAIN OUTCOME MEASURES: Pain score at rest as assessed by VAS. RESULTS: One hundred and fifty-three patients were included, of whom 140 were included in the final analysis (50 PCA, 44 TPVB, 46 CWC). Baseline and surgical characteristics were comparable in the three groups. VAS scores were statistically different between the TPVB and PCA groups at rest (at 0, 1, 3, 6 h; P < 0.0026) and after coughing (0, 1, 3, 6, 12 h; P < 0.003). In recovery room care, titrated morphine doses were significantly lower (P = 0.00001) in the TPVB group than in the other two. Morphine consumption was statistically lower in the TPVB group than in the PCA group at 24 h (P = 0.0036). There was no difference between CWC and PCA groups in terms of VAS scores or morphine consumption. No signs of toxicity or local complications were observed. CONCLUSION: Our results support the efficacy of TPVB for pain management after thoracotomy, at rest and after coughing. These results confirm the preference for TPVB over epidural analgesia in postthoracotomy pain care. CWC failed to decrease pain and morphine consumption and performed no better than placebo.

Surgical sealant for the prevention of prolonged air leak after lung resection: meta-analysis.

BACKGROUND: We performed a systematic and meta-analysis of randomized controlled trials comparing a surgical sealant with buttressed staple lines using standard methods. The aim of our meta-analysis was to determine the effectiveness and safety of different techniques to reduce the proportion of patients with prolonged air leakage after pulmonary resection. METHODS: We searched the Medline, Embase, Science Direct, Food and Drug Administration, Cochrane controlled trials register, and clinical trial databases for publications between January 1995 and May 2009 that included terms related to prolonged air leak after lung resection. We included randomized controlled trials comparing glue or patch or buttressed staple line with suture or staple in patients undergoing lung resection (wedge resection or lobectomy). The prespecified primary outcome of our meta-analysis was prolonged air leak more than 7 days. Secondary outcomes were the occurrence of adverse effects. RESULTS: Thirteen trials were included in the meta-analysis. Overall, the trials had allocated 1,335 patients to glue or patch (1,064 patients) or buttress (271 patients) for the prevention of prolonged air leak after lung resection. The type of buttress used to reinforce the staple line was bovine pericardial strips (271 patients). In the control group of all trials for air-leakage management, single or continuous running sutures or staples were used according to the routine of the center. The use of glue or a patch or buttressing compared with control groups (1,335 patients) decreased prolonged air leak more than 7 days. Indeed, the pooled effect size odds ratio was 0.55 (95% confidence interval: 0.386 to 0.79). An I(2) of 0% indicated low between-trial heterogeneity. The funnel-plot asymmetry coefficient was significantly different from zero (asymmetry coefficient -1.23 (95% confidence interval: -2.38 to -0.086; p < 0.04), indicating the presence of publication bias. Neither glue nor a patch nor buttressing influenced the occurrence of postoperative complications such as atelectasis, hemothorax, pneumonia, pneumothorax, and mortality. Eight trials (1,020 patients) showed that, compared with control groups, the use of glue or a patch or buttressing decreased postoperative arrhythmia, which yielded a pooled odds ratio of 0.44 (95% confidence interval: 0.275 to 0.72). CONCLUSIONS: The use of surgical sealants and buttressing decreased the risk of prolonged air leakage and postoperative arrhythmia after pulmonary resection. However, given the possibility of publication bias, the conclusions should be interpreted with caution.

Role of LTB4 in the pathogenesis of elastase-induced murine pulmonary emphysema.

Exaggerated levels of the leukotriene B4 (LTB4) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB4 pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB4 were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB4 in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA4 hydrolase-/- mice (LTB4 deficient, LTA4H-/-) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB4 in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA4H-/- mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA4H-/- mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH2O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA4H-/- mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA4H-/- mice were found to have significantly delayed influx of the CD45(high)CD11b(high)Ly6G(high) leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA4H-/- mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB4 played an important role in promoting the pathogenesis of pulmonary emphysema associated with neutrophilic pulmonary inflammation.