Abstract Introduction Whenever feasible, sleeve lobectomy is recommended to avoid pneumonectomy for lung cancer, but these guidelines are based on limited retrospective series. The aim of our study ...was to compare outcomes following sleeve lobectomy and pneumonectomy using data from a national database. Methods From 2005 to 2014, 941 sleeve lobectomy and 5318 pneumonectomy patients were recorded in the French database Epithor. Propensity score was generated with 15 pretreatment variables and used to create balanced groups with matching (794 matches) and inverse probability of treatment weighting (standardized difference was 0 for matching, and 0.0025 after weighting). Odds ratio (OR) of postoperative complications and mortality and hazard ratio (HR) for overall survival and disease-free survival were calculated using propensity adjustment techniques and a sensitivity analysis. Results Postoperative mortality after sleeve resection was similar to that after pneumonectomy (matching OR, 1.24; P = .4; weighting OR, 0.77; P = .4) despite significantly lower odds of pulmonary complications with pneumonectomy (matching OR, 0.4; P < .0001; weighting OR, 0.12; P < .001). The adjusted HR for death after pneumonectomy was significantly higher when analyzed using matched analysis but not with weighting (matching HR, 1.63; P = .002; weighting HR, 0.97; P = .92). The same was true for disease-free survival (matching HR, 1.49; P = .01; weighting HR, 1.03; P = .84). Conclusions Despite early differences in perioperative pulmonary outcomes favoring pneumonectomy, early overall and disease-free survival was in favor of sleeve lobectomy in the matched analysis but not the weighted analysis. In our opinion, when it is technically feasible, sleeve lobectomy should be the preferred technique.
Idiopathic pulmonary fibrosis (IPF) is characterized by an accumulation of extracellular matrix proteins and fibroblasts in the distal airways. Key developmental lung signaling pathways are ...reactivated in IPF. For instance, fibroblast growth factor 9 (FGF9) and FGF18, involved in epithelial-mesenchymal interactions, are critical for lung development. We evaluated the expression of FGF9, FGF18, and FGF receptors (FGFRs) in lung tissue from controls and IPF patients and assessed their effect on proliferation, survival, migration, and differentiation of control and IPF human lung fibroblasts (HLFs). FGF9, FGF18, and all FGFRs were present in the remodeled alveolar epithelium close to the fibroblast foci in IPF lungs. FGFR3 was generally detected in fibroblast foci by immunohistochemistry. In vitro, HLFs mainly expressed mesenchyme-associated FGFR isoforms (FGFR1c and FGFR3c) and FGFR4. FGF9 did not affect fibroblast proliferation, whereas FGF18 inhibited cell growth in control fibroblasts. FGF9 and FGF18 decreased Fas-ligand-induced apoptosis in control but not in IPF fibroblasts. FGF9 prevented transforming growth factor β1-induced myofibroblast differentiation. FGF9 and FGF18 increased the migratory capacities of HLF, and FGF9 actively modulated matrix metalloproteinase activity. In addition, FGFR3 inhibition by small interfering RNA impacted p-ERK activation by FGF9 and FGF18 and their effects on differentiation and migration. These results identify FGF9 as an antiapoptotic and promigratory growth factor on HLF, maintaining fibroblasts in an undifferentiated state. The biological effects of FGF9 and FGF18 were partially driven by FGFR3. FGF18 was a less potent molecule. Both growth factors likely contribute to the fibrotic process in vivo.
Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to ...describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS).
Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group. NGS was performed using an ampliseq panel to analyze hotspots and targeted regions in 22 cancer-associated genes. ALK, ROS1 and PD-L1 expressions were assessed by immunohistochemistry.
Squamous cell carcinoma was the most frequent histologic subtype in the IPF group (44%), adenocarcinoma was the most frequent subtype in the non-IPF group (62%). Forty-one mutations in 13 genes and one EGFR amplification were identified in 25 samples. Two samples had no mutation in the selected panel. Mutations were identified in TP53 (n = 20), MET (n = 4), BRAF (n = 3), FGFR3, PIK3CA, PTEN, STK11 (n = 2), SMAD4, CTNNB1, DDR2, ERBB4, FBXW7 and KRAS (n = 1) genes. No ALK and ROS1 expressions were identified. PD-L1 was expressed in 10 cases (62%) with only one (6%) case >50%.
This extensive characterization of lung fibrosis-associated cancers evidenced molecular alterations which could represent either potential therapeutic targets either clues to the pathophysiology of these particular tumors. These findings support the relevance of large molecular characterization of every lung fibrosis-associated cancer.
We evaluated the contribution of artificial intelligence in predicting the risk of acute cellular rejection (ACR) using early plasma levels of soluble CD31 (sCD31) in combination with recipient ...haematosis, which was measured by the ratio of arterial oxygen partial pressure to fractional oxygen inspired (PaO
/FiO
) and respiratory SOFA (Sequential Organ Failure Assessment) within 3 days of lung transplantation (LTx). CD31 is expressed on endothelial cells, leukocytes and platelets and acts as a "peace-maker" at the blood/vessel interface. Upon nonspecific activation, CD31 can be cleaved, released, and detected in the plasma (sCD31). The study included 40 lung transplant recipients, seven (17.5%) of whom experienced ACR. We modelled the plasma levels of sCD31 as a nonlinear dependent variable of the PaO
/FiO
and respiratory SOFA over time using multivariate and multimodal models. A deep convolutional network classified the time series models of each individual associated with the risk of ACR to each individual in the cohort.
Night work is frequently associated with sleep deprivation and is associated with greater surgical and medical complications. Lung transplantation (LT) is carried out both at night and during the day ...and involves many medical healthcare workers. The goal of the study was to compare morbidity and mortality between LT recipients according to LT operative time. We performed a retrospective, observational, single-center study. When the procedure started between 6 AM and 6 PM, the patient was allocated to the Daytime group. If the procedure started between 6 PM and 6 AM, the patient was allocated to the Nighttime group. Between January 2015 and December 2020, 253 patients were included. A total of 168 (66%) patients were classified into the Day group, and 85 (34%) patients were classified into the Night group. Lung Donors’ general characteristics were similar between the groups. The 90-day and one-year mortality rates were similar between the groups (90-days: n = 13 (15%) vs. n = 26 (15%), p = 0.970; 1 year: n = 18 (21%) vs. n = 42 (25%), p = 0.499). Daytime LT was associated with more one-year airway dehiscence (n = 36 (21%) vs. n = 6 (7.1%), p = 0.004). In conclusion, among patients who underwent LT, there was no significant association between operative time and survival.
Presence of anti-human leukocyte antigen donor-specific antibodies (DSAs) is associated with poor outcome after lung transplantation. Currently, DSAs are detected using the Luminex technique, which ...may be overly sensitive. The new C1q assay allows for the exclusive detection of complement (C1q)-binding antibodies, involved in antibody-mediated rejection. We investigated whether early detection of complement-binding DSAs is associated with chronic lung allograft dysfunction (CLAD) and survival.From 2009 to 2012, lung transplant recipients from three transplantation centres were screened for the presence of DSA and their complement-binding capacity during the 6-12 months post-transplantation in a stable condition.The analysis included 168 patients. The 3-year rates of freedom from CLAD and graft survival were lower for patients with complement-binding DSAs (33.6% and 53.7%, respectively), as compared with patients with non-complement-binding DSAs (61.9% and 77.4%, respectively) and patients without DSA (70% and 84.9%, respectively) (p<0.001 and p=0.001, respectively). Detection of complement-binding DSA was associated with a risk of graft loss that was nearly tripled after adjustment for clinical, functional, histological and immunological factors (hazard ratio 2.98, 95% CI 1.33-6.66; p=0.008).Assessment of the C1q-binding capacity of DSA appears to be useful in identifying stable lung transplant recipients at high risk of lung allograft loss.
Background N2 involvement has dramatic consequences on the prognosis and management of patients with non-small cell lung cancer (NSCLC). N2-NSCLC may present with or without N1 involvement, ...constituting non-skip (pN1N2) and skip (pN0N2) diseases, respectively. As the prognostic impact of this subclassification is still a matter of debate, we analyzed the prognosis of pN2 patients according to the pN1-involvement and the number of N2-stations concerned. Methods The medical records of consecutive patients who underwent surgery for pN2-NSCLC in 2 French centers between 1980 and 2009 were prospectively collected and retrospectively reviewed. Patients undergoing induction therapy, exploratory thoracotomy, incomplete mediastinal lymphadenectomy, or incomplete resections were excluded. The prognoses of pN1N2 and pN0N2 patients were first compared, and then deciphered according to the number of N2 stations involved (single-station: 1S, multi-station: 2S). Results All together, 871 patients underwent first-line complete surgical resection for pN2-NSCLC during the study period, including 258 pN0N2 (29.6%) and 613 pN1N2 (70.4%) patients. Mean follow-up was 72.8 ± 48 months. Median, 5- and 10-year survivals were, respectively, 30 months, 34%, and 24% for pN0N2 and 20 months, 21%, and 14% for pN1N2 patients ( p < 0.001). Multivariate analysis revealed 3 different prognostic groups; ie, favorable in pN0N2-1S disease, intermediate in pN0N2-2S and pN1N2-1S diseases, and poor in pN1N2-2S disease ( p < 0.001). Conclusions Among pN2 patients, the combination of N1 involvement (pN0N2 vs pN1N2) and number of involved N2 stations (1S vs 2S) are independent prognostic factors. These results might be taken into consideration to sub-classify the heterogeneous pN2-NSCLC group of patients.
Background It has been proposed that examining a greater number of lymph nodes (LNs) in patients with non–small-cell lung cancer (NSCLC) treated by surgical resection may increase the likelihood of ...proper staging and affect outcome. Our purpose was to evaluate the interindividual variability and prognostic relevance of the number of LNs harvested during complete pulmonary and mediastinal lymphadenectomy performed for NSCLC. Methods We prospectively collected and retrospectively reviewed the data from 1,095 patients who underwent lung cancer resection in association with systematic lymphadenectomy and pulmonary and mediastinal LN counts from 2004 to 2009. We analyzed the interindividual variability and prognostic impact of the number of LNs on overall survival (OS). Results The mean number of harvested pulmonary and mediastinal LNs was 17.4 ± 7.3 (range, 1–65) and was higher in male patients, right lung surgical procedures, lobectomy and pneumonectomy, N2 disease, and pIII stage. The mean number of harvested mediastinal LNs was 10.7 ± 5.6 and was normally distributed (range, 0–49; median, 10). The 5-year survival rate was 53.8%. Overall survival was influenced by the number of involved stations (single-station versus multi-station disease, 5-year survival rates 31.5% versus 16.9%, respectively; p =0.041) but not by the number of harvested LNs, the number of harvested mediastinal LNs, or the number of positive mediastinal LNs. Conclusions After lung cancer resection and complete lymphadenectomy, the number of LNs is subject to normally distributed interindividual variability, with no significant impact on OS. Recommending an optimal number of nodes is therefore arbitrary. Instead, our recommendation is to perform a complete systematic pulmonary and mediastinal lymphadenectomy following established anatomical boundaries.
Background: Peripheral femoro-femoral veno-arterial extracorporeal membrane oxygenation is increasingly used in refractory cardiogenic shock. However, the obstruction of the femoral artery by the ...return cannula could lead to acute limb ischemia, a frequently encountered situation that is inconstantly prevented by the adjunction of a distal perfusion cannula (DPC). The aim of this study was to investigate the influence of three physical parameters on the perfusion of the cannulated lower limb. Methods: Using patient-specific arterial models and computational fluid dynamic simulations, we studied four diameters of arterial cannula, three diameters of DPC, and two percentages of arterial section limitation. Results: We found that adequate perfusion of the cannulated limb was achieved in only two out of the twenty-one configurations tested, specifically, when the arterial cannula had a diameter of 17 Fr, was considered to limit the section of the artery by 90%, and was associated with an 8 Fr or a 10 Fr DPC. Multivariable analysis revealed that the perfusion of the cannulated lower limb was correlated with the diameter of the DPC, but also with the diameter of the arterial cannula and the percentage of arterial section limitation. Conclusions: In most of the cases simulated here, the current system combining unsized arterial cannula and non-specific DPC was not sufficient to provide adequate perfusion of the cannulated lower limb, urging the need for innovative strategies to efficiently prevent acute limb ischemia during peripheral femoro-femoral veno-arterial extracorporeal membrane oxygenation.
Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation (LTx). However, data concerning this approach remain limited.
We retrospectively reviewed the ...medical records of all patients in France who received ECMO as a bridge to LTx from 2007 to 2011. Post-transplant survival and associated factors were assessed by the Kaplan-Meier method and the Cox model.
Included were 36 patients from 11 centers. Indications for LTx were cystic fibrosis (CF) in 20 (56%), pulmonary fibrosis (PF) in 11 (30%), and other diagnoses in 5 (14%). ECMO was venovenous for 27 patients (75%) and venoarterial for 9 (25%). Mean follow-up was 17 months. Bridging to LTx was achieved in 30 patients (83%); however, only 27 patients (75%) survived the LTx procedure, and 20 (56%) were discharged from hospital. From ECMO initiation, 2-year survival rates were 50.4% overall, 71.0% for CF patients, 27.3% for PF patients, and 20.0% for other patients (p < 0.001). From LTx, 2-year survival rates were 60.5% overall, 71.0% for CF patients, 42.9% for PF patients, and 33.0% for other patients (p = 0.04).
Our study confirms that the use of ECMO as a bridge to LTx in France could provide a medium-term survival benefit for LTx recipients with critical conditions. Survival differed by underlying respiratory disease. Larger studies are needed to further define the optimal use of ECMO.
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