Abstract
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.
Abstract
OBJECTIVES
Severe compensatory hyperhidrosis (CH) is a disabling complication following thoracic sympathectomy. Our study was to establish valid patient selection criteria and determine ...outcomes of nerve reconstructive surgery. Furthermore, we assessed the clinical feasibility and safety of a robotic-assisted approach compared to video-assisted thoracoscopic surgery.
METHODS
Adults with severe CH following bilateral sympathectomy for primary hyperhidrosis were enrolled. We performed 2 questionnaires: the Hyperhidrosis Disease Severity Scale and the Dermatology Life Quality Index before and 6 months after nerve reconstructive surgery. A one-time evaluation of healthy volunteers (controls) was undertaken to validate the quality of life measures.
RESULTS
Fourteen patients (mean age 34.1 ± 11.5 years) underwent sympathetic nerve reconstruction. None of the patients had a recurrence of primary hyperhidrosis. Improvement in quality of life was reported in 50% of patients. Both mean Hyperhidrosis Disease Severity Scale and mean Dermatology Life Quality Index were significantly reduced compared to preoperative assessments. In 10 patients, a video-assisted approach and in 4 patients robotic assistance was utilized. There was no significant difference in outcomes between approaches.
CONCLUSIONS
Somatic–autonomic nerve reconstructive surgery offers a reversal in the debilitating symptoms in some patients with severe CH. Proper patient selection, preoperative counselling and management of expectation are of paramount importance. Robot-assisted thoracic surgery is an alternative method to conventional video-assisted surgery. Our study provides a practical approach and benchmark for future clinical practice and research.
Compensatory hyperhidrosis (CH) is a common adverse side effect following endoscopic thoracic sympathectomy (ETS) for primary hyperhidrosis 1.
Thoracic splenosis is the autotransplantation of splenic tissue in the left thoracic cavity as a result of a splenic injury. This rare pathology is usually asymptomatic and may be discovered on ...incidental imaging, but the diagnosis often requires invasive procedures such as surgery in order to eliminate a neoplasic origin. We report a rare symptomatic case of a 39-year-old man presenting with chest pain and multiple nodules revealed on a computed tomography scan. The patient underwent a surgical exploration and the pathological studies concluded to a thoracic splenosis. Indeed, the previous medical history of the patient revealed a left thoraco-abdominal traumatism during childhood. The aim of this paper is to emphasize that the diagnosis can now be performed using only imaging techniques such as technetium-99 sulfur colloid or labelled heat-denatured red blood cell scintigraphy to avoid unnecessary invasive procedures including thoracotomy.
Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after ...complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers.
Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed.
39 patients (M:F = 26:13), with a median age of 64 years (44-83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4-169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46-12.07,
= 0.008 and HR = 13.56, 95%CI 2.45-74.89,
= 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23-38.83,
= 0.002 and HR = 11.88, 95%CI 2.28-61.84,
= 0.003, respectively).
After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Up to now, no treatment can stop the progression of IPF. Vitamin D3 (VD) reduces experimental lung fibrosis ...in murine models and depletion of vitamin D3 might be associated with the reduced survival of patients with IPF. In this context, we determined if VD can prevent the pro-fibrotic functions of human lung fibroblasts (HLFs) isolated from patients with IPF. IPF and control HLFs were derived from surgical lung biopsies collected from patients with IPF or with primary lung cancer, respectively. VD (3-100 nM) markedly reduced the basal and PDGF-induced proliferation of HLFs. VD also altered cell cycle by increasing the percentage of IPF HLFs arrested in the G0/G1 phase, and by downregulating the expression of various cell cycle regulatory proteins. In addition, VD barely prevented the TGF-β1-induced differentiation in HLFs. At 100 nM, VD slightly reduced the expression of the pro-fibrotic marker α-smooth muscle actin, and had no effect on fibronectin and collagen-1 expression. In contrast, 100 nM VD strongly inhibited the aerobic glycolytic metabolism induced by TGF- β1. Finally, VD reduced both the secretion of lactate, the levels of lactate deshydrogenase mRNA and the activity of intracellular LDH in IPF HLFs. In conclusion, our study shows that VD reduced pro-fibrotic functions of HLFs. These findings suggest that it might be interesting to assess the potential clinical benefits of vitamin D supplementation in patients with IPF, especially on lung function decline.
The tyrosine kinase inhibitor nintedanib has been recently approved for the treatment of Interstitial Lung Diseases (ILDs) that manifest a progressive fibrosis phenotype other than Idiopathic ...pulmonary Fibrosis (IPF). Nintedanib reduces the development of lung fibrosis in various animal models resembling features of PF-ILD and in vitro, it inhibits the fibrosing phenotype of human lung fibroblasts (HLFs) isolated from patients with IPF. To get insight on the cellular and molecular mechanisms that drive the clinical efficiency of nintedanib in patients with non-IPF PF-ILD, we investigated its effects on the fibrosing functions of HLFs derived from patients with PF-hypersensitivity pneumonitis (PF-HP, n = 7), PF-sarcoidosis (n = 5) and pleuroparenchymal fibroelastosis (PPFE, n = 4). HLFs were treated with nintedanib (10 nM-1 μM) and then stimulated with PDGF-BB (25-50 ng/ml) or TGF-β1 (1 ng/ml) for 24-72 h to assess proliferation and migration or differentiation. At nanomolar concentrations, nintedanib reduced the levels of PDGF receptor and ERK1/2 phosphorylation, the proliferation and the migration of PF-HP, PF-sarcoidosis and PPFE HLFs stimulated with PDGF-BB. Moreover, nintedanib also attenuates the myofibroblastic differentiation driven by TGF-β1 but only when it is used at 1 μM. The drug reduced the phosphorylation of SMAD2/3 and decreased the induction of collagen, fibronectin and α-smooth muscle actin expression induced by TGF-β1. In conclusion, our results demonstrate that nintedanib counteracts fundamental fibrosing functions of lung fibroblasts derived from patients with PF-HP, PF-sarcoidosis and PPFE, at concentrations previously reported to inhibit control and IPF HLFs. Such effects may contribute to its clinical benefit in patients suffering from these irreversible ILDs.
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