[Congenital thoracic deformities and 3D custom-made implants. New classification based on a series of 789 treated cases]. / Malformations thoraciques congénitales et implants sur mesure 3D. Nouvelle classification basée sur une série de 789 cas traités.

The authors present a new study on 789 cases of congenital thoracic malformations including 638 pectus excavatum and 151 Poland syndromes, according to a new classification which completes Chin's one. All these malformations were treated with silicone elastomer implants. The contribution of computer-aided design and manufacturing (CAD/CAM) since 2008 is essential. The one-stage surgical protocol is precisely described. The results are impressive, permanent, for life, and complications are rare. The authors evoke a common vascular etiopathogenesis theory at the embryonic stage and question the heavy techniques of invasive remodeling that are most often unjustified.

[The pectus excavatum: Secondary surgery with implants]. / Le pectus excavatum : chirurgie secondaire par implants.

The pectus excavatum affects about one in 500 people. It is the most common malformation of the thorax. Several surgical or medical techniques have been proposed. Some are followed by complications or insufficient results. Secondary surgery with a deep customized 3D implant, may be an elegant and effective solution; it allows to obtain a good aesthetic result expected by patients in the absence of any respiratory or cardiovascular functional context.

[Different approaches to chest drainage in the management of primary spontaneous pneumothorax]. / Facteurs influençant la réussite du drainage pleural d'un premier épisode de pneumothorax spontané primitif.

Drainage of primary spontaneous pneumothorax (PSP) may be managed by different techniques and with different types of drain. It is mainly performed in the pneumology department or in the emergency department. The aim of the study was to evaluate the factors that influence the success of PSP drainage. This retrospective, monocentric study performed in University Hospital of Toulouse, included patients with a first episode of PSP requiring drainage. The primary outcome was the rate of success according to the techniques of drainage. Data on the size of the drain (>14F or<14F), the drainage technique (small bore catheter or chest tube drainage) and the drainage department (pneumology or emergency) were collected. One hundred and twenty-four patients had a drainage between 2014 and 2016: the late recurrence free success rate was 59% (n=73). Compared with emergency, drainage in pneumology increased the success rate threefold regardless of the drainage technique (P=0.0001) The success rate was similar whatever the technique used (Seldinger or classic technique) (P=0.31). Success and complications rates were similar whether the drain was large (>14F) or small (<14F) (respectively P=0.99 and P=0.58). In our study, the drainage of PSP in the pneumology department, with a small caliber inserted by the Seldinger technique, was associated with a significantly higher success rate.

3-month prognostic impact of severe acute renal failure under veno-venous ECMO support: Importance of time of onset.

PURPOSE: Veno-venous ECMO is increasingly used for the management of refractory ARDS. In this context, acute kidney injury (AKI) is a major and frequent complication, often associated with poor outcome. We aimed to identify characteristics associated with severe renal failure (Kidney Disease Improving Global Outcome (KDIGO) 3) and its impact on 3-month outcome. METHODS: Between May 2009 and April 2016, 60 adult patients requiring VV-ECMO in our University Hospital were prospectively included. RESULTS: AKI occurrence was frequent (75%; n=45), 51% of patients (n=31) developed KDIGO 3 - predominantly prior to ECMO insertion - and renal replacement therapy was required in 43% (n=26) of cases. KDIGO 3 was associated with a lower mechanical ventilation weaning rate (24% vs 68% for patients with no AKI or other stages of AKI; p<0.001) and a higher 90-day mortality rate (72% vs 32%, p=0.002). Multivariate logistic regression suggested that KDIGO 3 occurrence prior to ECMO insertion, as well as PaCO2>57mmHg and mSOFA>12 were independent risks factors for 90-day mortality. CONCLUSION: KDIGO 3 AKI occurrence is correlated with the severity of patients' clinical condition prior to ECMO insertion and is negatively associated with 90-day survival.

[An analysis of treatment delays of thoracic cancers: a prospective study]. / Analyse des délais de prise en charge des cancers thoraciques: étude prospective.

INTRODUCTION: Lung cancer is the main cause of cancer death in France. The diagnosis is often late and the delay between the onset of symptoms and management is considered an aggravating factor. MATERIAL AND METHODS: Our prospective study collected the dates of the start of management of 139 consecutive patients receiving first line treatment for thoracic cancer in our hospital between November 2008 and May 2009. The aim of this study was to evaluate the delays in medical or surgical treatments in patients with thoracic cancer and to determine the cause of these delays. RESULTS: The median delay between the first abnormal chest X-ray and treatment was 9.6 weeks. The delays were significantly shorter in the late stages and in small cell cancer (P=0.001). There was a tendency for shorter delays in women and for longer delays in older patients. CONCLUSION: Evaluation of the delays in treatment, particularly in the early stages, is part of the quality control of management of these diseases.

[Evaluation of preoperative non-invasive ventilation in thoracic surgery for lung cancer: the preOVNI study GFPC 12-01]. / Évaluation de la ventilation non invasive préopératoire avant chirurgie de résection pulmonaire. Étude préOVNI GFPC 12-01.

BACKGROUND: Surgical resection is the best treatment for stage I and II non-small cell lung cancer. Despite an improvement in the perioperative management of cancer patients and specialization of surgical teams, morbidity and mortality remains significant. Non-invasive ventilation (NIV) is an effective therapeutic option in hypercapnic respiratory failure. It also improves functional and gasometric parameters when undertaken before surgery. The objective of the preOVNI study is to demonstrate that preoperative non-invasive ventilation for 7 days, at home, reduces the postoperative respiratory and cardiovascular complications of lung resection surgery, in a high-risk population. METHODS: A prospective, randomized, controlled open-labelled multicentric French study, under the supervision of the Groupe Français de Pneumocancérologie (GFPC), comparing 7 days of preoperative non-invasive ventilation with standard treatment. Inclusion criteria are: patients suitable for lobectomy or segmentectomy for primary bronchial carcinoma and presenting with obstructive or restrictive lung disease, obesity or chronic cardiac insufficiency. The primary criterion is a composite one, including all respiratory and cardiac complications. The number of patients is 150 in each treatment arm, 300 in total. EXPECTED RESULTS: We think that preoperative NIV will be able to reduce the rate of postoperative complications. If this objective is achieved, the management of these patients could be changed.

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

DNA replication stress response involving PLK1, CDC6, POLQ, RAD51 and CLASPIN upregulation prognoses the outcome of early/mid-stage non-small cell lung cancer patients.

Lung cancer is the leading cause of cancer deaths worldwide. Clinical staging classification is generally insufficient to provide a reliable prognosis, particularly for early stages. In addition, prognostic factors are therefore needed to better forecast life expectancy and optimize adjuvant therapeutic strategy. Recent evidence indicates that alterations of the DNA replication program contribute to neoplasia from its early stages and that cancer cells are frequently exposed to endogenous replication stress. We therefore hypothesized that genes involved in the replication stress response may represent an under-explored source of biomarkers. Expressions of 77 DNA replication-associated genes implicated in different aspects of chromosomal DNA replication, including licensing, firing of origins, elongation, replication fork maintenance and recovery, lesion bypass and post-replicative repair were determined in primary tumors and adjacent normal tissues from 93 patients suffering from early- or mid-stage non-small cell lung cancer (NSCLC). We then investigated a statistically significant interaction between gene expressions and survival of early-stage NSCLC patients.The expression of five genes, that is, POLQ, PLK1, RAD51, CLASPIN and CDC6 was associated with overall, disease-free and relapse-free survival. The expression levels are independent of treatment and stage classification. Except RAD51, their prognostic role on survival persists after adjustment on age, sex, treatment, stage classification and conventional proliferation markers, with a hazard ratio of 36.3 for POLQ (95%CI 2.6-517.4, P=0.008), 23.5 for PLK1 (95%CI 1.9-288.4, P=0.01), 20.7 for CLASPIN (95%CI 1.5-275.9, P=0.02) and 18.5 for CDC6 (95%CI 1.3-267.4, P=0.03). We also show that a five-gene signature including POLQ, PLK1, RAD51, CLASPIN and CDC6 separates patients into low- and high-risk groups, with a hazard ratio of 14.3 (95% CI 5.1-40.3, P<0.001). This 'replication stress' metamarker may be a reliable predictor of survival for NSCLC, and may also help understand the molecular mechanisms underlying tumor progression.

[Surgical management of COPD distension]. / Prise en charge chirurgicale de la distension thoracique au cours de la BPCO.

INTRODUCTION: The impressive results seen when giant and compressing lung bullae are resected has inspired pneumonologists and thoracic surgeons to consider the possibility of applying a similar approach to the treatment of respiratory failure due to chronic obstructive pulmonary disease (COPD). STATE OF THE ART: The major problem with this surgical indication lies in our ability to understand fully the pathophysiology of lesions and thus identify which emphysematous patients will have a response most similar to that achieved in purely bullous disease. PERSPECTIVES: At the present time consideration should be given as to whether surgery is the only means of reducing pulmonary distension. Indeed, as endoscopic alternatives develop could they reproduce its beneficial effects and what would be their place compared to the surgery? CONCLUSIONS: While waiting the development of these innovations, if the selection of the candidates is correct, the surgical treatment of lung hyperinflation can temporarily improve the quality of life of these patients by decreasing their dyspnea and increasing their exercise tolerance.

[Lung cancer in women and pregnancy: towards a hormonal origin?]. / Cancer bronchique de la femme et de la femme enceinte: vers une origine hormonale?

INTRODUCTION: The incidence of lung cancer is increasing dramatically in women in France. It is now the leading cause of cancer deaths among women in the USA and the second in France. STATE OF THE ART: Lung cancer occurring in women displays some specific epidemiological, radiological, clinical and pathological characteristics. Moreover, both prognosis and response to treatment appear to be different from men. In line with these findings, lung carcinogenesis is, at least in part, distinct in women and involves different mechanisms and signalling pathways. We emphasize in this review genetic and hormonal specificities based upon epidemiological and biological studies. Moreover, we focus on lung cancer developing during pregnancy by reporting an individual case and discussing the published literature. PERSPECTIVES AND CONCLUSIONS: Recent works suggest that lung cancer in women is a distinct entity with specific carcinogenesis. We propose that a better knowledge of this entity will permit the identification of specific genetic alterations or hormonal profiles that may serve as new therapeutic targets.

[Surgical management and outcomes of lung cancer in women - results from the Epithor database]. / Particularités de la prise en charge chirurgicale du cancer bronchique chez la femme. Données de la base nationale Epithor.

INTRODUCTION: Rates of lung cancer in women have been increasing continually for several years. The basic surgical management of this condition is the same in both sexes but a number of differences are apparent. METHODS: We analysed data entered onto the Epithor database between June 2002 and June 2006 concerning 8535 surgical resections performed in primary lung cancer. RESULTS: 22.5 percent of patients were women. They were significantly younger (59.6 years vs 62.7 years) and had a lower BMI (24.7 kg x m(-2) vs 25.5 kg x m(-2)). They were in a better physical condition in terms of American Society of Anaesthesiology score and performance status, with better preserved lung function and fewer co-morbidities (1.8 vs 2.1) compared to men. The percentage of adenocarcinomas was higher in women and a higher proportion had early stage disease. 30 day mortality was three times as high in men who also experienced much greater post-operative morbidity. Multivariate analysis revealed an odds ratio of 0.49 (95% CI 0.3-0.8) for mortality and 0.54 (95% CI 0.4-0.6) for morbidity in women compared to men. CONCLUSION: Women with lung cancer have less risk of post-operative morbidity and mortality than men. These data suggest that they might be able to benefit from more aggressive perioperative therapy.

[Late complications of a pseudo aneurysm of the left ventricle: thrombus infection and purulent pericarditis]. / Complications tardives d'un faux anévrisme du ventricule gauche: infection du thrombus et péricardite purulente.

Pseudoaneurysm is a rare complication of left ventricle myocardial infarction. Rupture with tamponade and sudden death is the usual outcome. Surgical intervention remains the treatment of choice. Long term survival cases without surgery are rare. Infection of the thrombus is also a possible event. We report the case of a patient with postinfarction left ventricular pseudoaneurysm complicated by infection of the thrombus and purulent pericarditis involving a peptostreptococcus. Infection must be considered a potential complication of left ventricular pseudoaneurysms.

Understanding the oestrogen action in experimental and clinical atherosclerosis.

Whereas hormone replacement/menopause therapy (HRT) in postmenopausal women increases the coronary artery risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of oestradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favours an anti-inflammatory effect in vitro (cultured cells), it rather elicits in vivo a proinflammation at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. Endothelium is another important target for E2, as it potentiates endothelial NO and prostacyclin production, thus promoting the beneficial effects as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appears to be involved in the atheroprotective effect of E2. E2 also accelerates endothelial regrowth, thus favouring vascular healing. Finally, most of these effects of E2 are mediated by oestrogen receptor alpha, and are independent of oestrogen receptor beta. In summary, a better understanding of the mechanisms of oestrogen action not only on the normal and atheromatous arteries, but also on innate and adaptive immune responses is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective oestrogen receptor modulators.

Estradiol action in atherosclerosis and reendothelialization.

Whereas hormonal replacement/menopause therapy (HRT) in postmenopausal women increases coronary artery disease risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of estrogens is thus required. The atheroprotective effect of E2 is absent in mice deficient in mature T and B lymphocytes, demonstrating the crucial role of the endothelium/immune system pair. The immunoinflammatory system appears to play a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favors an anti-inflammatory effect in vitro (cultured cells), it elicits in vivo a proinflammation at the level of several subpopulations of the immunoinflammatory system, which could contribute to plaque destabilization. Endothelium appears to be an important target for E2, since it potentiates endothelial NO and prostacyclin production, thus promoting beneficial effects such as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appear to be involved in the atheroprotective effect of E2, which also accelerates endothelial regrowth, thus favoring vascular healing. Finally, most of these E2 effects are mediated by estrogen receptor alpha and are independent of estrogen receptor beta. In summary, a better understanding of the mechanisms of estrogens on the normal and atheromatous arteries is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective estrogen receptor modulators (SERMs).

Detection of oncogenic virus genomes and gene products in lung carcinoma.

We investigated a series of 122 cases of small cell lung carcinomas and non-small cell lung carcinomas for the presence of several viruses that are known to be oncogenic in humans. Thus, viral genomes (DNA) and/or RNA transcripts and/or proteins of human papillomaviruses (HPV) 16, 18, 31, 33, 51, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), human cytomegalovirus (HCMV) and simian virus 40 (SV40) were investigated on tissue sections (prepared in tissue microarrays) with different techniques of immunohistochemistry and in situ hybridisation. None of the cases displayed a single positive tumour cell for all the viruses tested whatever the technique applied. Of note, in five cases of tumours with lymphoid infiltrates, we detected scattered EBV (EBER)-positive bystander lymphocytes. In three cases, a faint nuclear staining was found with the anti-latent nuclear antigen/LANA1 (HHV-8) antibody. These cases were checked by PCR with two sets of primers (orf 26 and orf 75) and remained negative for this latter virus. Taken together, our data strongly suggest that the conventional human oncogenic viruses (HPV, EBV, HCMV, HHV-8 and SV40) are unlikely to play some role in the development of lung carcinomas..