The microbiota includes different microorganisms consisting of bacteria, fungi, viruses, and protozoa distributed over many human body surfaces including the skin, vagina, gut, and airways, with the ...highest density found in the intestine. The gut microbiota strongly influences our metabolic, endocrine, and immune systems, as well as both the peripheral and central nervous systems. Recently, a dialogue between the gut and lung microbiota has been discovered, suggesting that changes in one compartment could impact the other compartment, whether in relation to microbial composition or function. Further, this bidirectional axis is evidenced in an, either beneficial or malignant, altered immune response in one compartment following changes in the other compartment. Stimulation of the immune system arises from the microbial cells themselves, but also from their metabolites. It can be either direct or mediated by stimulated immune cells in one site impacting the other site. Additionally, this interaction may lead to immunological boost, assisting the innate immune system in its antitumour response. Thus, this review offers an insight into the composition of these sites, the gut and the lung, their role in shaping the immune system, and, finally, their role in the response to lung cancer.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Extended resection for lung cancer may improve survival of selected patients. Left-atrial resection is infrequently performed and surgical techniques are rarely reported; thus, oncologic ...results and survival rates remain uncertain. Our study describes surgical techniques, postoperative outcomes, and oncologic results of patients who received a combined multimodality treatment. Methods Between October 2004 and March 2012 in our institution, 19 patients underwent extended lung resection involving the left atrium without cardiopulmonary bypass. We reviewed perioperative treatments, surgical procedures, and postoperative morbidity, mortality, and long-term survival rates. Results Sixteen patients (68.4%) underwent neoadjuvant treatment including chemotherapy or radiotherapy. Eighteen pneumonectomies (94.7%) were performed, of which 12 (63.1%) were right sided. Dissection of the interatrial septum was complete in 4 patients (33.3%). Complete resection was achieved in 17 patients (89.4%) and 2 other patients (10.5%) were considered R1. The T-status was pT4 in all patients. Overall postoperative morbidity was 52.6%. The 30-day mortality rate was 10.5% and the 90-day mortality rate was 15.7%. Fifteen patients (93.7%) underwent adjuvant treatment. The mean follow-up time was 32.5 months. The 5-year probability of survival was 43.7%. Three patients (15.7%) were alive at greater than 6 years postsurgery. Conclusions Extended lung surgery with partial resection of the left atrium is a feasible procedure with acceptable morbidity. An interatrial septum dissection, by increasing the length of the atrial cuff, allows complete resection. Long-term survival can be achieved in highly selected patients who have undergone multimodal therapy.
We investigated the effects of betaine, C-phycocyanin (C-PC), and their combined use on the growth of A549 lung cancer both in vitro and in vivo. When cells were coincubated with betaine and C-PC, an ...up to 60% decrease in viability was observed which is significant compared to betaine (50%) or C-PC treatment alone (no decrease). Combined treatment reduced the stimulation of NF-κB expression by TNF-α and increased the amount of the proapoptotic p38 MAPK. Interestingly, combined treatment induced a cell cycle arrest in G2/M phase for ~60% of cells. In vivo studies were performed in pathogen-free male nude rats injected with A549 cells in their right flank. Their daily food was supplemented with either betaine, C-PC, both, or neither. Compared to the control group, tumour weights and volumes were significantly reduced in either betaine- or C-PC-treated groups and no additional decrease was obtained with the combined treatment. This data indicates that C-PC and betaine alone may efficiently inhibit tumour growth in rats. The synergistic activity of betaine and C-PC on A549 cells growth observed in vitro remains to be further confirmed in vivo. The reason behind the nature of their interaction is yet to be sought.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Few randomized controlled trials have been published on outcomes after treatment of spontaneous pneumothorax. The objective of this study was to assess recurrence, pulmonary complications, ...prolonged air leak, and hospital duration of stay in patients undergoing videothoracoscopic surgery (VATS) or thoracotomy for spontaneous pneumothorax. Methods From January 2005 to December 2012, 7,396 patients underwent operations for spontaneous pneumothorax and were entered into the French national database. The propensity score, which is the conditional probability of assignment to a particular treatment given a vector of observed covariates, was used for the analysis. Three statistical analyses were performed: matching, subclassification, and the inverse probability of treatment weighting. The primary end point was recurrence, defined as a pneumothorax requiring a chest tube or new operation. The secondary end point was pulmonary complications, prolonged air leak, and hospital duration of stay. Results VATS was performed in 6,419 patients and thoracotomy in 997 patients. Pleurodesis was performed by abrasion or pleurectomy in 5,873 patients (79%) and by using a chemical agent in 1,523 patients (21%). The median time to recurrence was 3 months (range, 1 to 76 months). The recurrence rate was higher in the VATS group regardless of the statistical analysis that was used: 2.1 for unmatched samples, 2.5 for matched samples, 2.3 for subclassification, and 1.7 for the inverse probability of treatment weighting. VATS significantly reduced the hospital duration of stay by 1 day but did not significantly reduce pulmonary complications or prolonged air leak. Conclusions VATS reduced the hospital duration of stay, but the risk of recurrence was higher. This information should be delivered to patients before pneumothorax operations.
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.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Loss of muscle mass worsens many diseases such as cancer and renal failure, contributes to the frailty syndrome, and is associated with an increased risk of death. Studies conducted on ...animal models have revealed the preponderant role of muscle proteolysis and in particular the activation of the ubiquitin proteasome system (UPS). Studies conducted in humans remain scarce, especially within renal deficiency. Whether a shared atrophying programme exists independently of the nature of the disease remains to be established. The aim of this work was to identify common modifications at the transcriptomic level or the proteomic level in atrophying skeletal muscles from cancer and renal failure patients.
Methods
Muscle biopsies were performed during scheduled interventions in early‐stage (no treatment and no detectable muscle loss) lung cancer (LC), chronic haemodialysis (HD), or healthy (CT) patients (n = 7 per group; 86% male; 69.6 ± 11.4, 67.9 ± 8.6, and 70.2 ± 7.9 years P > 0.9 for the CT, LC, and HD groups, respectively). Gene expression of members of the UPS, autophagy, and apoptotic systems was measured by quantitative real‐time PCR. A global analysis of the soluble muscle proteome was conducted by shotgun proteomics for investigating the processes altered.
Results
We found an increased expression of several UPS and autophagy‐related enzymes in both LC and HD patients. The E3 ligases MuRF1 (+56 to 78%, P < 0.01), MAFbx (+68 to 84%, P = 0.02), Hdm2 (+37 to 59%, P = 0.02), and MUSA1/Fbxo30 (+47 to 106%, P = 0.01) and the autophagy‐related genes CTPL (+33 to 47%, P = 0.03) and SQSTM1 (+47 to 137%, P < 0.01) were overexpressed. Mass spectrometry identified >1700 proteins, and principal component analysis revealed three differential proteomes that matched to the three groups of patients. Orthogonal partial least square discriminant analysis created a model, which distinguished the muscles of diseased patients (LC or HD) from those of CT subjects. Proteins that most contributed to the model were selected. Functional analysis revealed up to 238 proteins belonging to nine metabolic processes (inflammatory response, proteolysis, cytoskeleton organization, glucose metabolism, muscle contraction, oxidant detoxification, energy metabolism, fatty acid metabolism, and extracellular matrix) involved in and/or altered by the atrophying programme in both LC and HD patients. This was confirmed by a co‐expression network analysis.
Conclusions
We were able to identify highly similar modifications of several metabolic pathways in patients exhibiting diseases with different aetiologies (early‐stage LC vs. long‐term renal failure). This strongly suggests that a common atrophying programme exists independently of the disease in human.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Thoracic duct (TD) cyst is an uncommon abnormality that can be manifested as a cervical swelling. Pathogenesis includes congenital or degenerative weakness of the wall of the TD and obstruction of ...the lymphoid flow. Diagnosis is crucial to eliminate malignant disease or vein thrombosis and can be established by imaging and needle aspiration. We report a case of recurrent cervical swelling with spontaneous chylothorax and chyloperitoneum. A TD cyst with a terminal obstruction of the TD was diagnosed on lymphangiography. Treatment by microsurgical lymphovenous anastomosis was successful, and the patient was free of symptom 3 years later.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still ...lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients.
We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV
) or diffusing capacity of the lung for carbon monoxide (
) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients.
Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV
and
above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV
and/or preoperative
below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%)
1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10%
3.18% respectively).
By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV
or
below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.
Acquired emphysema is a rare pathology in pediatrics. We report the case of a patient born at term with a neonatal respiratory distress, which had required mechanical ventilation. She developed ...gradually chronic obstructive pulmonary disease with severe emphysematous lesions, respiratory failure and functional impairments. Bilateral emphysema resection, performed at 16 years old, allowed major functional benefits at rest and during exercise. We present the results of respiratory functional evaluations, walk tests and maximal exercise tests (including measure of dynamic hyperinflation) before and after surgery, which highlights that surgery is a successful option in the treatment of compressive emphysema in childhood.
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