Recommendations for Post-Operative RadioTherapy After Complete Resection of Thymoma-a French DELPHI Consensus Initiative.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT. METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement. RESULTS: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years. CONCLUSION: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

French recommendations for the diagnosis and management of lymphangioleiomyomatosis.

BACKGROUND: The present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France. METHODS: Practical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases. RESULTS: Lymphangioleiomyomatosis is a rare lung disease characterised by a proliferation of smooth muscle cells that leads to the formation of multiple lung cysts. It occurs sporadically or as part of a genetic disease called tuberous sclerosis complex (TSC). The document addresses multiple aspects of the disease, to guide the clinicians regarding when to suspect a diagnosis of lymphangioleiomyomatosis, what to do in case of recurrent pneumothorax or angiomyolipomas, what investigations are needed to make the diagnosis of lymphangioleiomyomatosis, what the diagnostic criteria are for lymphangioleiomyomatosis, what the principles of management are, and how follow-up can be organised. Recommendations are made regarding the use of pharmaceutical specialties and treatment other than medications. CONCLUSION: These recommendations are intended to guide the diagnosis and practical management of pulmonary lymphangioleiomyomatosis.

Prediction of survival after a lung transplant at 1 year (SALTO cohort) using information available at different key time points.

OBJECTIVES: A lung transplant is the final treatment option for end-stage lung disease. We evaluated the individual risk of 1-year mortality at each stage of the lung transplant process. METHODS: This study was a retrospective analysis of patients undergoing bilateral lung transplants between January 2014 and December 2019 in 3 French academic centres. Patients were randomly divided into development and validation cohorts. Three multivariable logistic regression models of 1-year mortality were applied (i) at recipient registration, (ii) the graft allocation and (iii) after the operation. The 1-year mortality was predicted for individual patients assigned to 3 risk groups at time points A to C. RESULTS: The study population consisted of 478 patients with a mean (standard deviation) age of 49.0 (14.3) years. The 1-year mortality rate was 23.0%. There were no significant differences in patient characteristics between the development (n = 319) and validation (n = 159) cohorts. The models analysed recipient, donor and intraoperative variables. The discriminatory power (area under the receiver operating characteristic curve) was 0.67 (0.62-0.73), 0.70 (0.63-0.77) and 0.82 (0.77-0.88), respectively, in the development cohort and 0.74 (0.64-0.85), 0.76 (0.66-0.86) and 0.87 (0.79 - 0.95), respectively, in the validation cohort. Survival rates were significantly different among the low- (< 15%), intermediate- (15%-45%) and high-risk (> 45%) groups in both cohorts. CONCLUSIONS: Risk prediction models allow estimation of the 1-year mortality risk of individual patients during the lung transplant process. These models may help caregivers identify high-risk patients at times A to C and reduce the risk at subsequent time points.

When to proceed to surgical rib fixation?-A single-institution clinical experience.

Background: Surgical rib fixation for multiple rib fractures and flail chest has become more common in the 2000s with interesting results in selected patients. However, surgical rib fixation lacks a consensus on the delay to surgery and the benefits on postoperative clinical outcomes. Our goal was to determine if delay to surgery can affect postoperative outcomes. Methods: We analyzed a retrospective database including all consecutive patients referred for surgical rib fixation. All outcomes were explored according to trauma mechanism, associated lesions, initial ventilatory status, delay to surgery, surgical technique and a specific focus was made towards post-operative care and pulmonary complications. Logistic regressions were performed to evaluate the association between delay to surgery [before 48 hours (early group), 48 hours to 7 days (mid group), more than 7 days (late group)] and pneumonia and failure of extubating. Results: From 2010 to 2020, 159 patients underwent surgical rib fixation. The median hospital length of stay was 18 days (interquartile range, 13-30 days). Pulmonary infections were encountered in 67 patients (42.2%) with about two third of early pneumonia (<5 days). The one-month mortality rate was 1.9%. Delay to surgery was not associated with either pneumonia (P>0.05) or failure of extubating (P>0.05). Conclusions: Surgical rib fixation can be delayed without increasing the risk of pulmonary complications. Stabilizing other clinical situations can be safely prioritized if needed. A global evaluation including characteristics of trauma and lung evaluation must be considered before surgical stabilization of rib fracture.

Role of the occupational disease consultant in the multidisciplinary discussion of interstitial lung diseases.

BACKGROUND: Diffuse interstitial lung diseases (ILD) constitute a heterogeneous group of conditions with complex etiological diagnoses requiring a multidisciplinary approach. Much is still unknown about them, particularly their relationship with occupational exposures. The primary objective of this study was to investigate the distribution of occupational exposures according to type of ILD. The secondary objectives were to estimate the proportion of ILDs possibly related to occupational exposure and to evaluate the added value of the participation of an occupational disease consultant in ILD multidisciplinary discussions (MDD). METHODS: From May to December 2020, all consecutive patients with ILD whose cases were reviewed during a MDD in a referral centre for ILD were prospectively offered a consultation with an occupational disease consultant. RESULTS: Of the 156 patients with ILD whose cases were reviewed in MDD during the study period, 141 patients attended an occupational exposure consultation. Occupational exposure was identified in 97 patients. Occupational exposure to asbestos was found in 12/31 (38.7%) patients with idiopathic pulmonary fibrosis (IPF) and in 9/18 (50.0%) patients with unclassifiable fibrosis. Occupational exposure to metal dust was found in 13/31 (41.9%) patients with IPFs and 10/18 (55.6%) patients with unclassifiable fibrosis. Silica exposure was found in 12/50 (24.0%) patients with autoimmune ILD. The link between occupational exposure and ILD was confirmed for 41 patients after the specialist occupational consultation. The occupational origin had not been considered (n = 9) or had been excluded or neglected (n = 4) by the MDD before the specialised consultation. A total of 24 (17%) patients were advised to apply for occupational disease compensation, including 22 (15.6%) following the consultation. In addition, a diagnosis different from the one proposed by the MDD was proposed for 18/141 (12.8%) patients. CONCLUSIONS: In our study, we found a high prevalence of occupational respiratory exposure with a potential causal link in patients with ILD. We suggest that a systematic specialised consultation in occupational medicine could be beneficial in the ILD diagnostic approach.

Subtotal Pleurectomy with Intrathoracic Chemo Hyperthermia (HITHOC) for IVa Thymomas: De Novo Versus Recurrent Pleural Disease.

INTRODUCTION: Stage IVa thymoma is a rare disease without a standard of care. Subtotal pleurectomy and HITHOC introduced in highly selected patients may provide interesting oncologic results. The purpose of this study was to distinguish de novo stage IVa tumors (DNT) from distant relapse (DR) with respect to post-operative and long-term outcomes to provide the procedure efficacy. METHODS: From July 1997-December 2021, 40 patients with IVa pleural involvement were retrospectively analyzed. The surgical procedure was subtotal pleurectomy and HITHOC (cisplatin 50 mg/m2, mitomycin 25 mg/m2, 42 °C, 90 min). The post-operative outcome, disease-free interval (DFI) and overall survival (OS) were analyzed. RESULTS: Mean age was 52 ± 12 years. B2 and B3 thymomas were preponderant (27; 67.5%). The median number of pleural nodes were nine (4-81) vs. five (1-36); p = 0.004 * in DNT and DR, respectively. Hospital mortality rate was 2.5%. There were four specific HITHOC complications (10%). DFI were 49 and 85 months (p = 0.02 *), OS were 94 and 118 months (NS), in DNT and DR, respectively. CONCLUSIONS: Subtotal pleurectomy with HITHOC in IVa offers satisfying results in highly selected patients, for both DNT and DR. Due to the disease rarity, multicentric studies are needed to define HITHOC as a standard of care.

Futile lobectomies following video-thoracoscopic exploration for indeterminate pulmonary nodules: a retrospective study.

Background: Lung cancer screening is correlated with an increase in detection of small indeterminate pulmonary nodules and these nodules often require operative resection to obtain the diagnosis. In suspected early-stage lung cancer, video-assisted thoracoscopic surgery (VATS) has become the preferred option. In this context of minimally invasive surgery, diagnostic wedge resection is sometimes difficult to perform for small deep impalpable nodules. So, our purpose was to determine whether performing VATS for indeterminate pulmonary nodule increases the risk of lobectomy for benign lesions. Methods: A retrospective analysis was carried out in our center from January 2013 to January 2019 on patients who underwent resection for a solitary pulmonary nodule suspicious for cancer. Resection method, frozen section analysis, post-operative outcomes, operative and pathology reports were reviewed. Results: Six hundred fifty-one patients underwent surgical exploration for a solitary pulmonary nodule. Thirty hundred and forty-five patients underwent VATS and 306 patients underwent thoracotomy. Patients in the VATS group underwent significantly more wedge resections (P=0.012) and diagnosis of lung cancer was significantly more frequent in the thoracotomy group (P<0.001). One hundred and thirty-two patients (38.3%) in the VATS group and 60 patients (19.6%) in the thoracotomy group underwent lobectomy without frozen section analysis of the pulmonary nodule. There was no significant difference in terms of lobectomy performed for a benign lesion between the two groups. Conclusions: VATS was associated with a higher rate of benign lesion resection but was not associated with a higher rate of lobectomies for benign lesion in our study.

Evolution of the Surgical Management of Lung Cancer Invading the Spine: A Single Center Experience.

For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications during one step surgery. The aim of our study was to assess postoperative morbimortality and long-term survival of both techniques. We retrospectively reviewed all patients who underwent en bloc resection for lung cancer invading the spine between October 2012 and June 2020. Every patient underwent induction therapy. Sixteen patients were included: nine patients were operated on with one step surgery, seven patients were operated on with two step interventions. Twenty-five percent of patients had major perioperative complications and 56.2% of patients had major post-operative complications. Patients in the "one step" group tended to have more perioperative complications whereas patients in the "two step" group tended to have more post-operative complications. Overall 3-year survival was 40% in the one-step and 86% in the two-step surgery group. Although our practice has been improved by two-step interventions, post-operative morbidity remains significant. As long term survivals are encouraging, this type of treatment should still be proposed for highly selected patients, in specialized centers.

Clinical practices for non-neoplastic thymic lesions: Results from a multidisciplinary cohort.

BACKGROUND: Non-neoplastic thymic lesions are uncommon findings that corresponds to multiple histological and clinical entities that may be difficult to differentiate from thymic malignancies. In this study, our main objective was to describe the clinical, imaging and pathological characteristics of non-neoplastic thymic lesions in a large cohort of patients. We also aimed at understanding the key factors that led to a decision to surgically resect those lesions. METHODS AND MATERIALS: This is an observational, retrospective study. We enrolled both patients with non-neoplastic thymic lesions - normal thymus, thymic lymphoid/non-lymphoid hyperplasia, and thymic cysts - that had been pathologically-confirmed after surgical resection - , and patients with a thymic lesion that was never operated, based on imaging follow-up. RESULTS: A total of 128 patients were included, 88 of whom underwent surgical resection of the lesion (69%), and 40 patients (31%) had follow-up without surgery. Discovery of the lesion was incidental in 69 (54%) cases; thoracic magnetic resonance imaging was performed in 33 (26%) cases, 85% of which showed apparent decrease in the lesion signal intensity in phase opposition at chemical shift sequences. In the 88 operated patients, there were 34 (39%) normal thymuses, 29 (33%) lymphoid hyperplasias, 6 (7%) non-lymphoid thymic hyperplasias, and 19 (22%) thymic cysts. In the 40 non-operated patients, a major driver for the decision of follow-up was the decrease in the lesion signal intensity in phase opposition at chemical shift sequences, observed in 68% of cases; imaging follow-up of these lesions showed sustained regression in the majority of the cases. CONCLUSIONS: The management of benign thymic lesions requires multidisciplinary assessment. A strategy that integrates clinical and imaging features, including chemical-shift sequences at magnetic resonance imaging, as well as follow-up, allows a better selection of the patients for surgery.

Impact of ex vivo lung perfusion on brain-dead donor lung utilization: The French experience.

Ex vivo lung perfusion (EVLP) is a valuable method for expanding the lung donor pool. Its indications currently differ across centers. This national retrospective cohort study aimed to describe the profile of donors with lungs transplanted after EVLP and determine the effectiveness of EVLP on lung utilization. We included brain-dead donors with at least one lung offered between 2012 and 2019 in France. Lungs transplanted without or after EVLP were compared with those that were rejected. Donor group phenotypes were determined with multiple correspondence analysis (MCA). The association between donor factors and lung transplantation was assessed with a multivariable multinomial logistic regression. MCA revealed that donors whose lungs were transplanted after EVLP had profiles similar to the donors whose lungs were declined and quite different from those of donors with lungs transplanted without EVLP. Donor predictors of graft nonuse included age ≥50 years, smoking history, PaO2 /FiO2 ratio ≤300 mmHg, abnormal chest imaging, and purulent secretions. EVLP increased utilization of lungs from donors with a smoking history, PaO2 /FiO2 ratio ≤300 mmHg, and abnormal chest imaging.

Intestinal Air in the Mediastinum.

CASE PRESENTATION: A 74-year-old man, in excellent physical condition and doing regular intense cycling, was evaluated for transient episodes of thoracic discomfort over a period of several months. His medical history only included a right inguinal hernia, surgically treated, and an abdominal aortic aneurysm measured at 46 mm and treated medically. Physical examination did not reveal much information. The patient did not report gastroesophageal reflux, dysphagia, or history of digestive occlusion. The patient had normal weight and had no trauma history. He had no nicotine or alcohol-dependent behaviors. Vital signs were within normal values. Laboratory test results were normal. Functional status was normal, without anomalies of pulmonary function tests or arterial blood gases. The ECG did not reveal any anomaly.

Central Nervous System Metastases in Thymic Epithelial Tumors: A Brief Report of Real-World Insight From RYTHMIC.

Thymic epithelial tumors (TETs) are rare malignancies ranging from indolent thymoma A to aggressive thymic carcinomas (TCs). Brain metastases are extremely infrequent for TETs and have only been described in case reports or small single-center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network mandated to systematically review every TET case and prospectively includes all consecutive patients discussed by national or regional tumor boards. We analyzed patients with TETs and central nervous system (CNS) metastasis during their cancer history from this large French registry. In an 8-year period, 2909 patients were included in the database, including 248 TCs (8.5%). A total of 14 patients had CNS metastases, five (36%) at diagnosis and nine (64%) at relapse. Among them, 12 patients (86%) had a diagnosis of TC and two (14%) had thymoma A and B3. Surgical biopsies were performed, and the histologic subtype for non-TC tumors was centrally confirmed. Median overall survival was 22 months (95% confidence interval [CI]: 9.8-34.2), with longer, albeit not significant, overall survival when CNS metastases were present at diagnosis versus relapse (not reached versus 17 mo; p = 0.29); median progression-free survival was 13 versus 8 months (p = 0.06), respectively. A higher risk of death (hazard ratio = 5.34, 95% CI: 1.3-21.9, p = 0.02) and relapse (hazard ratio = 1.89, 95% CI: 0.9-3.7, p = 0.06) was observed for patients suffering from TC with brain metastases compared with those without CNS extension. CNS disease was extremely rare in our TET cohort (0.48%), reported at both diagnosis and progression, present primarily in TC, with prevalence rising to 4.9%.

Epicardial carvernous hemangioma: The diagnostic challenge of a middle mediastinal mass.

Primary tumors in the middle mediastinum are rare and pose diagnostic challenges. Lymphomas, mediastinal cysts and thymomas most frequently affect this anatomic area. Primary cardiac tumors are rare and constitute a differential diagnosis for the inferior middle mediastinum. Surgical exploration and resection is often mandatory in order to make a definitive diagnosis. Here, we report the case of a 69 year-old women who presented with persistent dyspnea. A complete preoperative workup revealed a large tissular mass adjacent to the right atrium. A diagnosis of a typical epicardial cavernous hemangioma was made following surgical resection.

Lymph Node Dissection in Thymoma: Is it worth it?

OBJECTIVES: Lymph node dissection (LND) and nodal metastases in thymomas remain controversial and understudied. The aim of our study was to evaluate the incidence of nodal metastasis and the short term outcomes of systematic LND in thymomas. MATERIAL AND METHODS: From December 2017 to September 2020, we performed 54 LND conducted according to the International Thymic Malignancy Interest Group (ITMIG) lymph node map. This group was compared to a historical control group of 55 patients who underwent surgery in our center from January 2015 to November 2017. RESULTS: LND was performed in 72 % and in 5 % of the cases in the study cohort group and historical control group, respectively. The number of lymph nodes retrieved was significantly higher in the study cohort group (3.89 per patient vs. 1.62, p = 0.0021). In the whole population studied, nodal metastases were found in 3 patients (2.8 % of all patients) with 5.6 % in the cohort study group vs. 0 % in the control group (p = 0.12). Patients with nodal metastasis had larger tumors (> 7 cm), and a higher histology grade (B2 and B3). There was a trend towards higher risk of laryngeal nerve palsy in the cohort study group (9.3 % vs. 1.8 %, p = 0.11). CONCLUSION: Systematic LND increases the number of lymph node harvested and detects more lymph node metastases, which remains infrequent in thymomas. The impact of LND and the true prognostic significance of lymph node metastases remains controversial. Given the potential complications, LND or sampling should not be perfomed in small, encapsulated and low grade thymomas.

Impact of Lung Biopsy on Lung Function in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Video-assisted surgical lung biopsy (SLB) is performed in 10-30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF). OBJECTIVES: The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF. METHODS: This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB. RESULTS: In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline. CONCLUSION: In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year.

Uncommon EGFR mutations in lung adenocarcinoma: features and response to tyrosine kinase inhibitors.

BACKGROUND: EGFR mutant non-small cell lung cancer (NSCLC) is a heterogeneous disease. The treatment for frequent EGFR mutations relies on tyrosine kinase inhibitors (TKIs); the clinical and therapeutic significance of uncommon EGFR mutations is uncertain. METHODS: This is a single-center retrospective study of patients with EGFR-mutant lung cancer (2009-2017). Molecular analyses of EGFR exons 18-21 were performed. Only patients with uncommon mutations were included (p.Glu709X, p.Gly719X, p.Ala767_Val769 dup, p.Ser768Ile, and p.Leu861Gln). RESULTS: Among 6,747 tumor samples, 95 out 820 patients (11.6%) harbored 113 uncommon EGFR mutations. There were 50 metastatic NSCLC patients for whom the median OS was 18.0 months (95% CI: 15, 32). In this population, the p.Leu861Gln uncommon exon 21 EGFR mutation was associated with poor prognosis (HR: 2.96, 95% CI: 1.39, 6.31; P=0.003). Among those harboring a single uncommon EGFR mutation, median OS was 27.6 months (95% CI: 10.8, not attained) in patients who were treated by chemotherapy only (n=13) versus 6.0 months (95% CI: 2.4, not attained) in patients exclusively treated with a first or second-EGFR-TKI (n=9; HR: 0.27, 95% CI: 0.09, 0.78; P=0.01. In patients with a single uncommon EGFR mutation, first-line chemotherapy was associated with a better overall survival than TKIs (HR: 0.31, 95% CI: 0.15, 0.68; P=0.002). In patients who received first or second-EGFR-TKI as first-line treatment (n=26), OS was significantly better for those with two uncommon EGFR mutations than those with a single uncommon mutation (HR: 0.07, 95% CI: 0.009, 0.54; P=0.001). CONCLUSIONS: In conclusion, uncommon EGFR mutations may be associated with a poor outcome and the data challenge the use of first-generation TKI in such patients, however first-line TKI is more effective in cases of double uncommon mutations and such patients should be treated accordingly.

Combined Single Lung and Liver Transplantation in a Cystic Fibrosis Patient With Previous Contralateral Pneumonectomy: A Case Report.

Combined lung-liver transplantation is a rare life-saving procedure to treat concomitant end-stage lung and liver failure. In this report, we describe the first published case of single lung and liver transplantation in a cystic fibrosis patient who had previously undergone a pneumonectomy for the treatment of an infected and destroyed right lung. We detail the lung first, sequential transplant procedure and surgical difficulties due to mediastinal shift. Emergent intraoperative renal replacement therapy was carried out before liver transplantation to overcome pulmonary edema in the transplanted lung. After fluid balance equilibration, liver transplantation was performed in good conditions. The patient is currently alive with no signs of rejection 8 years after the procedure.

Frequency of MET exon 14 skipping mutations in non-small cell lung cancer according to technical approach in routine diagnosis: results from a real-life cohort of 2,369 patients.

BACKGROUND: Mesenchymal epithelial transition receptor (MET) alterations, including MET exon 14 skipping mutation, are oncogenic in non-small cell lung cancer (NSCLC) and may confer sensitivity to targeted therapy. Given the rarity and the diversity of exon 14 skipping mutations, diagnosis may be challenging on small-biopsy specimens. METHODS: Between March 2014 and May 2018, tissue samples from patients with metastatic NSCLC were analysed for MET exon 14 skipping mutation as part of routine practice in the Pathology Department of the Hospices Civils de Lyon, France. Over the study period, Sanger sequencing and/or two different DNA-based next generation sequencing (NGS) assays were used. RESULTS: Genomic alterations of MET exon 14 were detected in 2.6% (62/2,369) samples of NSCLC analysed for MET exon 14 mutations. Patients were mainly women (38/62, 61%) without smoking history (22/39, 56%) and the median age was 75 years. MET exon 14 skipping mutations were diagnosed by NGS in 50 cases and by classical Sanger sequencing in 12 cases. The frequency of MET mutations was 15.4% when Sanger sequencing was performed at the request of the clinician and 4.1% when the DNA-based NGS assay coverage included the 3' and 5' parts of the MET exon 14 and performed systematically. CONCLUSIONS: The frequency of genomic alterations is highly dependent on patient selection and the technical approach.

Airway complications after lung transplantation: benefit of a conservative bronchoscopy strategy.

BACKGROUND: After lung transplantation (LT), between 2% and 25% of bronchial anastomoses develop complications requiring therapeutic intervention. The status of healing of both bronchial anastomoses and downhill airways are well described by the French consensual MDS standardized grading system (Macroscopic, Diameter, Suture). We analyzed risks factors for airway complications (AC) after transplantation and the way we managed them. We report here our challenging method of early rigid bronchoscopic intervention with airway stenting on bronchial healing. METHODS: All single center consecutives LTs were retrospectively analyzed between 2010-2016. Patient-level data (demographic, peri-operative data) and anastomosis-level data (surgical parameters, bronchoscopy findings) were monitored. The incidence and contributive factors of ACs are reported. We also reported modalities of the conservative treatment and outcome. RESULTS: A total of 121 LTs were performed, 39 single-lung and 82 bilateral sequential LT. Main indication for LT were cystic fibrosis (45%) and emphysema (25%) and 58 were male patients (n=70). After a waiting period of healing, 28 patients presented AC on 41 anastomoses (prevalence: 23%). A multivariate analysis found as contributive factors of ACs, post-operative infection by Aspergillus [odds ratio (OR) 2.7, 95% confidence interval (CI): 1.08-6.75; P=0.033] at the patient level, and at the anastomosis level, emphysema (OR 2.4, 95% CI: 1.02-5.6; P=0.045), early dehiscence (OR 11.2, 95% CI: 1.7-76; P=0.01) and cold ischemia time >264 min (OR 2.45, 95% CI: 1.08-5.6; P=0.03). All the 41 ACs were managed conservatively with rigid bronchoscopy (range, 1-10), 41 stents (21 in silicone and 20 fully-covered Silicone Expandable Metallic Stents) without major complication. Two AC were still under regular bronchoscopic care and silicone stenting for long left bronchus reason. No surgical intervention was needed. The 2-years overall survival rate where not different between AC group and controls, respectively 85% and 81%. CONCLUSIONS: Airway healing after transplantation remains a scalable process and the French consensual MDS classification helped us for therapeutic decisions. Rigid bronchoscopy and safety use of current stenting devices may have the pivotal role in the conservative management of ACs, avoiding perilous situation of surgery for AC. Despite a high rate of AC, their favorable evolution may be explained by the cautious care of airway healing and maybe by the use of the Celsior antioxidant solution.

Bone decalcification to assess programmed cell death ligand 1 expression in bone metastases of non-small cell lung cancers.

As for molecular alterations of lung adenocarcinoma, it is critical that pathologists are able to give PD-L1 expression status before first-line of treatment. The present study compared PD-L1 expression (clone 22-C3) in decalcified using EDTA or formic acid and non-decalcified lung cancer metastases bone samples. Amongst the 84 bone samples analysed for PD-L1 expression, and independently of decalcification, TPS ≥ 1% was 25.0% and ≥ 50% was 11.4%. There was no significant difference between decalcified samples (n = 45) and non-decalcified samples (n = 39) for both TPS ≥ 1% (p = 0.32) and TPS ≥ 50% (p = 1). To conclude, we confirm decalcified bone metastasis specimens may be used for PD-L1 IHC in routine practice. These results also highlight potentially interesting specificities of the bone microenvironment that should be further studied.