[Evolution and progress of lung transplantation: An analysis of a cohort of 600 lung transplant patients at the Hospital Foch]. / Évolution et progrès en transplantation pulmonaire : étude de la cohorte de 600 premiers patients transplantés pulmonaires à l'hôpital Foch.

Lung transplantation is deemed to be the only effective therapy that improves survival for patients with end stage lung disease. The aim of our study was to examine the progress achieved over the last two decades and to demonstrate the effectiveness and safety of this treatment. METHODS: A retrospective analysis of a cohort of 600 consecutive lung transplant patients treated at the hospital Foch (Suresnes, France) between 1988 and 2014. They were split into three groups of 200 patients each: 1988-2004, 2004-2011, 2011-2014. RESULTS: Time and mortality on waiting list, perioperative mortality, the incidence of acute rejection in the first year and chronic lung allograft dysfunction (CLAD) at 5 years posttransplantation, have all decreased. Global survival at 1 and 5 years for the 600 patients increased from 78% and 57% to 86% and 75% respectively for the 200 last patients. Patients with cystic fibrosis have a better 5 year survival than those with emphysema or pulmonary fibrosis (68% vs. 54 % for emphysema and 37% for fibrosis). For the last 200 patients, 5 year survival is 81% for CF patients, 78 % for emphysema and 47% for fibrosis. Emergency transplantation had a 60% 5 years survival. Proliferative complications, arterial hypertension and renal function impairment are being monitored long term. CONCLUSION: The twenty-five years experience shows a consistent improvement in the results of lung transplantation which is now accepted as the only effective curative treatment for end stage lung disease.

[What place for lung volume reduction surgery for emphysema?] / Quelle place pour la réduction de volume pulmonaire chirurgicale dans l'emphysème ?

Lung volume reduction surgery (LVRS) has been part of the management for the treatment of selected emphysematous patients for two decades. In a large randomized American trial (NETT), lung volume reduction surgery was shown to improve overall survival at 5 years as well as exercise capacity and health-related quality of life, especially in cases of upper-lobe-predominant emphysema and low exercise capacity. Inclusion criteria were pretreatment FEV1≤45 %, TLC≥100 %, RV≥150 %, room air resting PaCO2≤60mmHg and PaO2≥45mmHg. Patients with FEV1≤20 % and either a DLCO<20 % or homogeneous emphysema were at increased risk of mortality following LVRS and should not be considered for this procedure. Despite this evidence base, lung volume reduction surgery is performed infrequently, competing with lung transplantation and new endoscopic volume reduction techniques.

[Helical tomotherapy in the treatment of malignant pleural mesothelioma: The impact of low doses on pulmonary and oesophageal toxicity]. / Tomothérapie hélicoïdale dans le traitement du mésothéliome pleural malin : impact des faibles doses sur la toxicité pulmonaire et œsophagienne.

PURPOSE: To evaluate the adjuvant treatment of malignant pleural mesothelioma by helical tomotherapy and the impact of low doses on esophageal and pulmonary toxicity. PATIENTS AND METHODS: Between June 2007 and May 2011, 29 patients diagnosed with malignant pleural mesothelioma received adjuvant radiotherapy by helical tomotherapy. The median age was 63 years (34-72). Histologically, 83 % of patients had epithelioid malignant pleural mesothelioma. Clinically, 45 % of patients were T3 and 55 % N0. Eighty six percent of the patients were treated by extrapleural pneumonectomy and 35 % received neoadjuvant chemotherapy with platinum and pemetrexed. The median dose in the pneumonectomy cavity was 50Gy at 2Gy/fraction. RESULTS: The mean follow-up was 2.3 years after diagnosis. Overall survival at 1 and 2 years was 65 and 36 % respectively. The median survival from diagnosis was 18 months. Median lung volumes receiving 2, 5, 10, 13, 15 and 20Gy (V2, V5, V10, V13, V15 and V20) were 100, 98, 52, 36, 19 and 5 %. The median of the mean remaining lung dose was 11Gy. Two patients died of pulmonary complications, three patients had grade 3 lung toxicity, while esophageal grade 3-4 toxicity was observed in three other patients. No significant impact of clinical characteristics and dosimetric parameters were found on pulmonary toxicity, however a V10≥50 %, a V15≥15 % and mean lung dose of 10Gy or more had a tendency to be predictive of pulmonary toxicity (P<0.1). Moreover, in our analysis, the mean lung dose seems to have a significant impact on esophageal toxicity (P=0.03) as well as low doses to the controlateral lung: V5, V10 and V13 (P<0.05). CONCLUSION: Helical tomotherapy is a promising technique in the multimodality treatment of malignant pleural mesothelioma. Low doses received by the contralateral lung appear to be the limiting factor. A dosimetric comparison with volumetric modulated arctherapy techniques would be interesting in this setting.

[Chemo-radiotherapy before surgery in stage III non-small-cell lung cancer]. / La chimio-radiothérapie néoadjuvante dans le cancer bronchique de stade III.

Surgery is often performed when N2 non-small-cell lung cancer can be resected by lobectomy since the publication of the "EORTC 08941" and "RTOG 9309" trials (the latter showed high mortality rate after pneumonectomy). The usefulness of adjuvant chemotherapy has been proved, and that of modern adjuvant radiotherapy is suspected, but neoadjuvant chemotherapy is also routinely performed in France. Neoadjuvant chemo-radiotherapy is more accepted in the USA and northern Europe. Four randomized trials have not shown any advantage in comparison with neoadjuvant chemotherapy, due to increased postoperative mortality, but retrospective studies in specialized centers have demonstrated low operative risks, even after high-dose radiation, or pneumonectomy. In the case of invasive apical tumors, neoadjuvant chemo-radiotherapy is recommended. In case of local recurrence without distant recurrence after exclusive chemo-radiotherapy, curative surgery may be envisaged.

[Non-small cell lung cancer with oligometastases: treatment with curative intent]. / Cancers bronchiques non à petites cellules avec oligométastases : prise en charge chirurgicale à visée curative.

Published series suggest that, in carefully selected patients, long-term survival can be obtained when a complete resection of the primary site and metastasis is achieved. It comprises resection of additional malignant nodules in the contralateral lung (at present classified as M1a, but the additional nodule may be a second primary lung cancer), complete resection of the primary associated with limited metastatic pleural involvement (M1a), and resection of the primary with an isolated extrathoracic metastasis (mostly a single brain or adrenal). All these topics are discussed.

[Indications for surgery in non-small cell lung cancer with lymph node invasion]. / Place de la chirurgie dans le cancer bronchique avec métastases ganglionnaires. Un plaidoyer chirurgical.

Surgery is indicated for N1 non-small cell lung cancer and performed, with good results in some patients, when N2 disease is not diagnosed preoperatively "minimal N2". Following the publication of the "EORTC 08941" and "Intergroup 0139" trials, it remains debatable for patients with proven N2 disease. Good prognostic factors before treatment or post-induction favour surgery, which seems superior to radiochemotherapy if the operative risk is low (lobectomies, and some pneumonectomies). N3 status is a contraindication to surgery, except in some rare cases with a strong response to induction treatment.

[Pleural mesothelioma: where are we with radical surgery and multimodal treatment?]. / Mésothéliome pleural : où en sont la chirurgie radicale et le traitement multimodal ?

Multimodal treatment of pleural mesothelioma, which is reserved for specialised centres for epithelial forms without node involvement, must include preliminary laparoscopy, thoracoscopy and mediastinoscopy. Following chemotherapy, in our opinion surgical removal via pleuropneumonectomy should be performed without resection of the diaphragm and the pericardium, because of the risks of seeding and postoperative complications. Our limited experience with 15 patients has confirmed the feasibility of this with no deaths. High-dose radiotherapy of the whole pneumonectomy cavity appears essential, but the optimal technique is debatable. Only five homogeneous series of more than 40 patients incorporating hemithoracic radiotherapy have been published.

[Lung surgery in haematological patients: useful? hazardous?]. / Chirurgie pulmonaire chez le malade d'hématologie : pourquoi ? Pour qui ?

Respiratory complications are frequent in haematological patients. Lung surgery, either for diagnosis or treatment, is considered useful but hazardous in these patients. We performed a reappraisal study of this purpose; retrospective study in a university centre, located in the Paris area, France. We analysed the entire records of all the haematological patients admitted in the Thoracic Surgery department from October 2001 to January 2009, among 400 haematological patients with pulmonary complications admitted to the Respiratory Diseases department. Seventeen patients (male: n=13, mean age 47 ± 15 years) underwent lung surgery. Underlying haematological disease was acute (n=7) or chronic (n=5) leukaemia, lymphoma (n=4), and eight have had stem cell transplantation. Thirteen patients had been exposed to a cytotoxic chemotherapy with known pulmonary toxicity. Respiratory diseases have been evolving for 112 days (10-663 days), and 14 patients received previously antibiotic and/or antifungal therapy. One patient was neutropenic and three had thrombopenia. Five patients underwent curative surgery for a residual pulmonary nodule after medical treatment of invasive aspergillosis, and 12 had a diagnostic procedure (open lung biopsy by video-assisted thoracoscopy [n=2]; thoracotomy [n=8]). Surgery permitted a final diagnosis in all 12 cases: non-specific infiltrative pneumonia (n=4), pulmonary graft versus host disease (n=3), granulomatous pneumocystosis (n=1), invasive aspergillosis (n=1), bronchial carcinoma (n=1), EBV-related lymphoproliferation (n=1), and tuberculosis (n=1). Therapeutic regimens were modified according to the surgical results in ten cases (84%). All patients were extubated at the end of surgery. Post-operative complications were: prolonged air leaks (n=3), pneumonia (n=1), parenchymal hematoma (n=1), acute coronary syndrome (n=1). Seven patients were admitted in the Intensive Care Unit, and five had non-invasive ventilation. Three patients died from respiratory failure: NSIP (n=2), pneumocystosis (n=1). Lung surgery for selected haematological patients has two indications: (1) curative surgery, for a residual pulmonary nodule after medical treatment of invasive aspergillosis; (2) diagnostic procedure, leading frequently to modifications of therapeutic regimens, with low rate of complications, in highly selected patients.

[Surgery for stage 1 lung cancer]. / Chirurgie des tumeurs pulmonaires de stade I.

Surgery is the present reference treatment for stage I non-small cell lung cancer. Lymph node dissection is required for mediastinal staging and discussion of postoperative treatments. In case of limited respiratory function, sub-lobar resection can be considered, either segmentectomy or atypical resection according to the tumour size. For radiological lesions with more than 50% of ground glass opacity, a wedge resection is acceptable if the resection margin is larger than 2 cm of healthy lung.

[Value of tomotherapy in malignant pleural mesothelioma: first clinical results]. / Intérêt de la tomothérapie après pleuro-pneumonectomie extrapleurale dans le mésothéliome pleural malin: premiers résultats cliniques.

INTRODUCTION: There is little clinical data about the place of helicoidal tomotherapy (HT) in the treatment of malignant pleural mesothelioma (MPM). This new form of intensity modulated radiotherapy (IMRT) has great theoretical advantages in large and complex volumes when compared to "traditional" forms of radiotherapy. PATIENTS AND METHODS: Fourteen patients diagnosed with MPM received adjuvant radiotherapy by HT. The patients were treated at the Curie Institute and the René Gauducheau Centre, starting in August 12007. All patients had a complete initial staging, an extrapleural pneumonectomy (EPP), and a minimum follow-up of six months. The median dose prescribed to the surgical cavity was 50 Gy (48-54 Gy) in 2 Gy (1.80-2.07) fractions. High dose regions received concomitant 57 Gy (54-69 Gy) in 2.16 Gy (2.00-2.30 Gy) fractions. RESULTS: Median follow-up was 12.6 months after ending HT. Seven patients received neoadjuvant chemotherapy (cisplatin or carboplatin, and pemetrexed). Eight patients were staged pT3 and five were staged pN1-2. HT was well tolerated. Two patients had suspected G5 radiation pneumonitis within 6 months of ending HT. Of the 12 patients who survived treatment, six relapsed (in average 5.1 months after HT): distant. Four relapses were distant; two relapses were both local and distant. Three patients died after their initial relapse. After initial diagnosis, the median survival was 18.4 months. A learning curve was observed in the optimization of the dosimetric parameters. CONCLUSION: Helicoidal tomotherapy is a reliable, quite well tolerated, and efficient way of treating MPM patients after an EPP.

[Logistic, technic and postoperative complications of lung and heart-lung transplantations]. / Logistique, technique et complications post-chirurgicales des transplantations pulmonaires et cardiopulmonaires.

In France, the "Agence de la biomédecine" distributes lung grafts. "Ideal" criteria for lung donor selection are not always respected, driven by the scarcity of suitable donor lungs (10% deaths while waiting). In single lung transplantation, three anastomoses are performed (bronchus near the lobar carina, pulmonary artery, left atrium). For double lung transplantation (twice as frequent around the world), two single lung transplantations are successively performed through two separate anterolateral thoracotomies, often without cardiopulmonary bypass. Heart lung transplantations are now rare (2% around the world). Postoperative mortality has improved (between 10 and 15%): less severe primary graft dysfunctions, treatable with ECMO, fewer bronchial complications, improvement in the diagnosis of hyperacute humoral rejection, improvement in antiviral prophylaxis.

Pulmonary vascular dysfunction in end-stage cystic fibrosis: role of NF-kappaB and endothelin-1.

Pulmonary hypertension is rare in chronic respiratory diseases but has a strong impact on the prognosis and is partly underlined by factors other than hypoxaemia. The aim of the present study was to assess the potential role of endothelin-1 (ET-1) and nuclear factor (NF)-kappaB vasoconstrictive pathways in pulmonary hypertension. The effects of ET-1 receptors blockers (BQ 123 and 788) and of genistein were assessed on response to acetylcholine of pulmonary vascular rings from cystic fibrosis (CF) lung transplant recipients (n = 23). NF-kappaB and ET-1 receptor expression was immunodetected in pulmonary arteries and quantitated using Western blotting. ET-1 vascular content was quantitated using ELISA. In total, 14 out of 23 subjects exhibited strongly impaired pulmonary vasodilation (p<0.01 versus nine out of 23 subjects with a normal response) associated with an activation of ET-1 receptors A and NF-kappaB pathways. Genistein restored vasodilation in subjects with an abnormal response. Pulmonary vascular dysfunction is frequent in end-stage CF, involving the NF-kappaB pathway and that of ET-1 through ET-1 receptor A (ETAR). These data leave a conceptual place for ETAR blockers and isoflavones in the management of the devastating vascular complication of chronic obstructive respiratory diseases such as CF.

Clinical outcome following lung transplantation in patients with cystic fibrosis colonised with Burkholderia cepacia complex: results from two French centres.

BACKGROUND: Infection with Burkholderia cepacia complex (BCC) is a life threatening complication of cystic fibrosis (CF), often seen as a contraindication for lung transplantation. METHODS: A long term retrospective study was conducted of all patients with CF undergoing lung transplants from January 1990 to October 2006 in two French centres allowing transplantation in patients colonised with BCC. RESULTS: 22 of the 247 lung transplant patients with CF were infected with BCC (B. cenocepacia genomovar III (n = 8), B. multivorans genomovar II (n = 11), B. vietnamiensis genomovar V (n = 2) and B. stabilis genomovar IV (n = 1)). BCC colonisation was not associated with any significant excess mortality (HR 1.5, 95% CI 0.7 to 3.2; p = 0.58). However, early mortality rates tended to be higher in the BCC group than in the non-BCC group (3 month survival: 85% vs 95%, respectively; log rank p = 0.05). Univariate analysis showed that the risk of death was significantly higher for the eight patients infected with B. cenocepacia than for the other 14 colonised patients (HR 3.2, 95% CI 1.1 to 5.9; p = 0.04). None of the other risk factors tested-primary graft failure, late extubation, septicaemia-had a significant effect. The 5 year cumulative incidence rate of bronchiolitis obliterans syndrome was not significantly higher in the BCC group than in the non-BCC group (38% vs 24%, respectively; p = 0.35). CONCLUSION: Our results suggest that BCC infection with a non-genomovar III organism may not be associated with excess mortality after lung transplantation in patients with CF and should not be seen as sufficient reason to exclude lung transplantation. However, colonisation with B. cenocepacia remains potentially detrimental.

[IFCT-0302 trial: randomised study comparing two follow-up schedules in completely resected non-small cell lung cancer]. / Protocole IFCT-0302: essai randomisé de deux schémas de surveillance dans les cancers bronchiques non à petites cellules complètement réséqués.

BACKGROUND: The authorities advocate a minimalist attitude towards the follow-up of resected bronchial carcinoma (clinical examination and chest x-ray). A survey showed that 70% of French respiratory physicians have chosen to use the CT scanner and often endoscopy. The published data are equivocal and are often based on retrospective studies. Lung cancer is a good model for a study of post-operative surveillance. Recurrences often occur in easily observed areas, they may be detected while still asymptomatic and are sometimes potentially curable. Second primary tumours may develop at the same site. METHODS: The Intergroupe Francophone de Cancerologie Thoracique (IFCT) has initiated a trial comparing simple follow-up (clinical examination, chest x-ray) with a more intensive follow-up (CT scan, fibreoptic bronchoscopy). The surveillance will take place every 6 months for 2 years and then annually until 5 years. EXPECTED RESULTS: The main aim is to determine whether intensive follow-up improves patient survival. The opposite question is equally important. If an expensive and demanding follow-up does not affect the chances of cure these results will influence our practice.

[Radical surgery for mesothelioma]. / La chirurgie radicale dans le mésothéliome.

Good results obtained by the team from Boston increased the interest in pleuropneumonectomy for mesothelioma. Adjuvant high-dose hemithoracic radiation after surgical resection decreased the local recurrence rate from 35 to 13%. The high rate of peritoneal (26-31%), controlateral pleural and pericardial recurrences justify the routine practice of preoperative laparoscopy and controlateral thoracoscopy and a pleuropneumonectomy without pericardotomy and diaphragmatic resection. The diaphragm is lowered to facilitate radiotherapy. Chemotherapy may be performed postoperatively.

[Lymph node clearance]. / Le curage ganglionnaire.

The goal of mediastinal sampling or a radical lymph node resection after lung cancer resection is to correctly stage the illness to enable a more accurate assessment of prognosis. Metastasis to mediastinal nodes may be encountered even in small peripheral T1 tumours. Radical lymph node resection often uncovers metastases that would have been missed by mediastinal sampling alone. The morbidity associated with radical node resection is very low, and long term survival appears to be improved, compared with node sampling. At present, lymph node staging has little influence on the choice of adjuvant treatments.

[Should lymph node extension be handled by curage or sampling?]. / Comment approcher l'extension ganglionnaire: curage ou sampling?

Between 10 and 20% of patients exhibiting normal mediastinum during surgery will present, on histology, invaded lymph nodes when complete curage is performed and, in 25% of cases the mediastinal lymph nodes may be invaded without involvement of the with the hilar lymph nodes. Moreover, such involvement of the mediastinum not uncommon in peripheral tumours. Hence it is clear that multiple mediastinal node samples should be taken. Should simple "sampling" be performed as is recommended by the Lung Cancer Study Group or lymph node curage? The morbidity inherent to curage and the fact that, despite several randomised studies, the impact of curage on survival has not been clearly demonstrated, explains the continued debate.

[The place of interventional endoscopy in the treatment of lung cancer]. / Place de l'endoscopie interventionnelle dans le traitement du cancer bronchique.

Interventional endoscopy, by eliminating an obstacle compromising the survival of a patient, has its place in the treatment of bronchial cancer whatever its stage of evolution. Forty percent of patients have not been treated yet, 30 still have therapeutic possibilities at the time of their relapse and for 30% all the possible treatments have been administered and interventional endoscopy remains their only chance of survival. A strict operational protocol ensures safety: operating theatre, general anaesthesia, rigid bronchoscopy, jet-ventilation, post-surgery ICU, and systematic post-surgery fibroscopy. Eighty percent of the patients retrieve normal ventilation. 12% are not sufficiently improved and 3% die either from uncontrollable haemorrhage or from the impossibility of repermeation. The nature of the tumour (primary bronchial cancer, metastasis at distance, invasion from a surrounding cancer) does not enter into the decision to intervene. The benefits of the latter are assessed by the pneumologist or oncologist who is in charge of the patient, but the final decision to intervene naturally remains with the endoscopist.

[Lung transplantation]. / Transplantations pulmonaires.

Lung transplantation is indicated for patients with cystic fibrosis, emphysema, pulmonary fibrosis or pulmonary hypertension whose life expectancy is less than two years. Criteria of severity are detailed. Three types of transplantation can be proposed: single lung transplant for fibrosis and dry emphysema; bilateral lung transplant for cystic fibrosis, and certain types of emphysema and pulmonary hypertension; heart-lung transplant for pulmonary hypertension and Eisenmenger syndrome. Due to insufficient supply of donor organs, one quarter of the candidates die on the waiting list and the limit for inscription is often 60 years. Postoperative mortality at two months is about 15% and is related to graft dysfunction, infection, bronchial complications,... Acute rejection usually occurs during the first year. Chronic rejection is expressed by obliterating bronchiolitis, the leading cause of death after one year. There is a risk of cancer (EBV-induced lymphoproliferative syndromes and skin cancer). Five-year survival is still only about 50%. Immunosuppressor treatments still cause numerous adverse effects (hypertension, renal toxicity...); function and quality-of-life have however greatly improved.