EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer.

BACKGROUND: Although EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some EGFR mutant tumors do respond to these therapies; however, there is a lack of understanding of the characteristics of EGFR mutant lung tumors responsive to immune checkpoint blockade. PATIENTS AND METHODS: We retrospectively analyzed de-identified clinical and molecular data on 171 cases of EGFR mutant lung tumors treated with immune checkpoint inhibitors from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, University of California Los Angeles, and Dana Farber Cancer Institute. A separate cohort of 383 EGFR mutant lung cancer cases with sequencing data available from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, and The Cancer Genome Atlas was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations. RESULTS: Compared with 212 EGFR wild-type lung cancers, outcomes with programmed cell death 1 or programmed death-ligand 1 (PD-(L)1) blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR (EGFRΔ19) but similar for EGFRL858R lung tumors. EGFRT790M status and PD-L1 expression did not impact response or survival outcomes to immune checkpoint blockade. PD-L1 expression was similar across EGFR alleles. Lung tumors with EGFRΔ19 alterations harbored a lower tumor mutation burden compared with EGFRL858R lung tumors despite similar smoking history. CONCLUSIONS: EGFR mutant tumors have generally low response to immune checkpoint inhibitors, but outcomes vary by allele. Understanding the heterogeneity of EGFR mutant tumors may be informative for establishing the benefits and uses of PD-(L)1 therapies for patients with this disease.

[Thymomectomy by minimally invasive surgery. Comparative study videosurgery versus robot-assisted surgery]. / Traitement des thymomes par chirurgie mini-invasive. Étude comparative vidéochirurgie versus voie robot-assistée.

OBJECTIVES: To report the results of minimally invasive surgery in patients with stage I or II thymoma in the Masaoka classification. The reference technique is partial or complete thymectomy by sternotonomy. METHODS: A retrospective single-center study of a prospective database including all cases of thymoma operated from April 2009 to February 2015 by minimally invasive techniques: either videosurgery (VATS) or robot-assisted surgery (RATS). The surgical technique, type of resection, length of hospital stay, postoperative complications and recurrences were analysed. RESULTS: Our series consisted of 22 patients (15 women and 7 men). The average age was 53 years. Myasthenia gravis was present in 12 patients. Eight patients were operated on by VATS and 14 patiens by RATS. There were no conversions to sternotomy and no perioperative deaths. The mean operating time was 92min for VATS and 137min for RATS (P<0.001). The average hospital stay was 5 days. The mean weight of the specimen for the VATS group was 13.2 and 45.7mg for the RATS group. Twelve patients were classified Masaoka stage I and 10 were stage II. According to the WHO classification there were 7 patients type A, 5 type AB, 4 type B1, 4 type B2 4 and 2 type B3. As proposed by the Group ITMIG-IASLC in 2015 all patients corresponded to group I. The mean follow-up period was 36 months. We noted 3 major perioperative complications according to the Clavien-Dindo classification: one pneumonia, one phrenic nerve paralysis and one recurrent laryngeal nerve palsy. We observed one case of local recurrence at 22 months. Following surgery 4 patients were treated with radiotherapy and 2 patients with chemotherapy. CONCLUSIONS: The minimally invasive route is safe, relatively atraumatic and may be incorporated in the therapeutic arsenal for the treatment of Masaoka stage I and II thymoma as an alternative to conventional sternotomy. RATS and VATS are two minimally invasive techniques and the results in the short and medium term are acceptable. The clinical advantages of one over the other are sifficult to establish. RATS could handle larger and more complex lesions in view of the weight and size of the operating instrument.

Simplified open repair for anterior chest wall deformities. Analysis of results in 205 patients.

INTRODUCTION: Pectus deformities are the most frequently seen congenital thoracic wall anomalies. The cause of these conditions is thought to be abnormal elongation of the rib cartilages. We here report our clinical experience and the results of a sternochondroplasty procedure based on the subperichondrial resection of the elongated cartilages. HYPOTHESIS: This technique is a valuable surgical strategy to treat the wide variety of pectus deformities. PATIENTS AND METHODS: During the period from October 2001 through September 2009, 205 adult patients (171 men and 34 women) underwent pectus excavatum (181), carinatum (19) or arcuatum (5) repair. The patients' pre and postoperative data were collected using a computerized database, and the results were assessed with a minimum 2-year follow-up. RESULTS: The postoperative morbidity rate was minimal and the mortality was nil. The surgeon graded cosmetic results as excellent (72.5%), good (25%) or fair (2.5%), while patients reported better results. Patients with pectus excavatum were found to have much more patent foramen ovale (PFO) than the normal adult population, which occluded after the procedure in 61% of patients, and significant improvement was found in exercise cardiopulmonary function and exercise tolerance at the 1-year follow-up. DISCUSSION: Our sternochondroplasty technique based on the subperichondrial resection of the elongated cartilages allows satisfactory repair of both pectus excavatum and sternal prominence. It is a safe procedure that might improve the effectiveness of surgical therapy in patients with pectus deformities.

[Cardiopulmonary exercise testing in patients with pectus excavatum]. / Exploration fonctionnelle à l'exercice des patients présentant un pectus excavatum.

The functional consequences of physiologic impairments due to pectus excavatum (PE) are not known. This study was conducted to determine the exercise performance in patients with this condition. This prospective study included all patients presenting for PE during a 5-year period. Patients had a chest CT scan to measure the PE severity index, resting pulmonary function tests, cardiopulmonary exercise testing (CPET) with gas exchange analysis and echocardiography. Thirty-two patients were included, with a mean age of 25.9 years. The mean PE severity index was 3.72 ± 0.87. The maximal oxygen uptake (VO(2-max)) was 78.6 ± 22.1% predicted. Only four out of the 32 patients had a normal CPET. In the remaining patients, we observed three main patterns of limitation: 18 patients had a marked limitation in increasing their tidal volume (41 ± 5% of FVC at VO(2-max) versus 51 ± 7.5%); five patients had abnormal gas exchange with increased P(A-a)O(2) at VO(2-max) (47 ± 23 mmHg versus 20 ± 7.5 mmHg) associated with a patent foramen ovale without elevation of right pressure. The five last patients had cardiovascular impairment with a decreased oxygen pulse at VO(2-max) (57 ± 9% versus 90 ± 20%). They exhibited the most severe limitation (VO(2-max) = 55 ± 10%; P = 0.003). CPET abnormalities were predicted by neither PE index severity nor the results of resting pulmonary function tests. PE is associated with abnormal CPET, including impairments in ventilatory, cardiovascular responses and/or gas exchange, which may be of importance in disease management.

[Malformations of the anterior chest wall]. / Malformations de la paroi thoracique antérieure.

INTRODUCTION: Pectus excavatum or funnel chest is the most common anterior chest wall deformity seen in children and adults. The sternal depression appears to be caused by overgrowth of the costal cartilages, also the cause of the less common deformities: pectus carinatum (pigeon breast) and pectus arcuatum. BACKGROUND: Usually the overgrowth involves the third to seventh costal cartilages but it can be more or less extensive. The cardiopulmonary functional consequences are insignificant in the protrusional deformities and inconsistent in pectus excavatum and the indications for surgery are mainly cosmetic. VIEWPOINT AND CONCLUSIONS: The procedural modalities are guided by morphological study of the CT scan. We describe a surgical technique that comprise subperichondrial excision of all deformed costal cartilages followed by transverse sternotomy to correct the sternal deformity, anteriorly in the case of pectus excavatum and posteriorly for pectus carinatum and arcuatum. As the perichondrial sheaths are totally preserved they are sutured in continuous layers to give a shortening effect. In the case of pectus excavatum the sternum is then secured anteriorly for about 6 months by a retrosternal metallic strut in an overcorrected position. The partially resected seventh cartilages are then sutured to the xiphoid. Other surgical techniques are described, including modified Ravitch's procedure, modelling osteochondroplasty, prosthetic reconstruction and Nuss's procedure. Results of the more important series are reported and discussed.

[Pulmonary zygomycosis in a patient treated for invasive aspergillosis]. / Zygomycose pulmonaire chez un patient traité pour une aspergillose invasive possible.

We report a pulmonary mucormycosis due to Absidia corymbifera. It occurred in a leukemic patient treated for a probable aspergillosis regressing after voriconazole treatment. The patient responded to surgery and a combination of liposomal amphotericin B and itraconazole. He was alive and well after 7-months of follow up.

Electrical readout of the local nuclear polarization in the quantum Hall effect: a hyperfine battery.

It is demonstrated that the now well-established "flip-flop" mechanism of spin exchange between electrons and nuclei in the quantum Hall effect can be reversed. We use a sample geometry which utilizes separately contacted edge states to establish a local nuclear spin polarization--close to the maximum value achievable--by driving a current between electron states of different spin orientation. When the externally applied current is switched off, the sample exhibits an output voltage of up to a few tenths of a mV, which decays with a time constant typical for the nuclear spin relaxation. The surprising fact that a sample with a local nuclear spin polarization can act as a source of energy and that this energy is well above the nuclear Zeeman splitting is explained by a simple model which takes into account the effect of a local Overhauser shift on the edge state reconstruction.

Aortoesophageal fistula of uncommon origin: perforation of a Barrett's ulcer.

Aortoesophageal fistulas are life-threatening conditions of which over half are secondary to thoracic aortic aneurysms. Four cases related to perforation of a Barrett's ulcer have been described so far, accounting for less than 1% of published aortoesophageal fistulas. We report a fifth case, which presented with severe hypotension, anemia and hematemesis. The patient underwent emergency esophagectomy and aortic closure but postoperatively required aortic endoprosthesis for residual bleeding. This case highlights the great diagnostic and therapeutic challenge associated with perforated Barrett's ulcer.

[Primary soft tissue sarcoma of the chest in adults: a retrospective study of 40 cases]. / Sarcomes des tissus mous thoraciques de l'adulte: étude rétrospective de 40 cas.

AIM OF THE STUDY: Primary thoracic soft tissue sarcomas (PTSTS) include parietal, pulmonary and mediastinal tumors. Management and prognostic factors of these rare tumors are poorly known. The aim of the study was to report a series of 40 patients with PTSTS, with analysis of their clinico-pathological characteristics, management, and prognostic factors. DESIGN: Data were collected from a prospective database. Survival were analyzed by Kaplan-Meier method and compared with log-rank test. Prognostic factors were identified with a Cox model. RESULTS: The median age was 48 years. The male/female ratio was 15/25. The most common subtype was malignant histiocytofibroma (11 cases). Twenty-one tumors were high-grade sarcomas. The commonest location was chest wall (26 cases). Thirty-two sarcomas were treated surgically, including 22 who had radical resections (free margins). Associated treatments were neoadjuvant (n = 8) or adjuvant (n = 8) chemotherapy, and postoperative radiotherapy (n = 17). The 5-year overall survival was 45%. In univariate analysis, prognostic factors were age (p = 0.05), Karnofsky index (p = 0.008), absence of metastases at initial presentation (p = 0.0003), radical resection (p = 0.043), and adjuvant chemotherapy (p = 0.04). The tumor location had no prognostic value. CONCLUSIONS: Management of PTSTS needs a multidisciplinary approach, and is mainly based on radical resection. Prognosis of pulmonary, chest wall and mediastinal sarcomas is similar.

[Experimental model of perinatal pulmonary circulation in lambs]. / Modèle d'étude de la circulation pulmonaire périnatale chez l'agneau.

STUDY AIM: Mechanisms that modulate fetal pulmonary circulation and transitional circulation at birth are incompletely understood. The aim of this experimental study was to describe an animal model in order to study the perinatal pulmonary circulation. MATERIAL AND METHODS: Pregnant ewes were operated on between 126 and 128 days gestation (term = 145 days). A skin incision was performed to the fetal lambs in utero and catheters were placed into the ascending aorta and the superior vena cava after insertion in the axillary artery and vein. Then, catheters were inserted into the left pulmonary artery (LPA), main pulmonary artery, and left atrium via a thoracotomy. Moreover, an ultrasonic flow transducer, and an inflatable vascular occluder were placed around the LPA and around the ductus arteriosus. During 10 days, studies were performed in utero (possibly continued when fetal lambs were delivered by caesarean section). This chronically prepared animal may be used to perform hemodynamic studies according to different protocols (drugs injection to the fetus or to the ewes, ductus arteriosus compression, oxygen test). The main pulmonary artery, aortic, left atrial and amniotic pressures, heart rhythm, and flow signal were continuously recorded. RESULTS: Eighteen pregnant ewes were operated on and nine only could be used for experimentation. This ovine model permitted several studies, particularly about effects of catecholamines on the pulmonary circulation, and about effects of ductus arteriosus compression on the pulmonary circulation. CONCLUSION: Chronically instrumented fetal lambs are an excellent model in order to study the perinatal pulmonary circulation.

Randomized controlled trial of a synthetic sealant for preventing alveolar air leaks after lobectomy.

BACKGROUND: The intraoperative application of synthetic surgical lung sealant (SLS) to surfaces leaking air or at risk of air leaks has been advocated to reduce alveolar air leaks (AAL) after lobectomy. METHODS: This study was designed to investigate the effectiveness of SLS in reducing AAL in patients considered intraoperatively to have moderate to severe AAL, after all conventional measures to reduce such leaks had been used. Over 17 months, 124 patients undergoing standard lobectomy were randomized to standard closure of parenchymal surgical sites, with or without SLS. RESULTS: In treated patients, the mean numbers of intraoperative AAL after application of SLS were significantly smaller than in untreated patients (38.5 mL versus 59.9 mL, p = 0.0401). Postoperatively, the mean time to last observable AAL was shorter in the treated group (33.7 hours versus 63.2 hours, p = 0.0134) and the mean percentage of patients free of AAL at days 3 and 4 was smaller (87% versus 58.5%, p = 0.002). However, the occurrence of incomplete lung expansion after drain removal, and the length of the postoperative hospital stay due to prolonged AAL, were not different. In the treatment group, 4 patients developed localized empyema and incomplete lung expansion without bronchopleural fistula 7, 12, 15, and 20 days, respectively, after operation. In these 4 patients, inserted chest tubes drained infected sealant. CONCLUSIONS: Surgical lung sealant may be a useful adjunct to conventional techniques for reducing moderate and severe AAL after lobectomy, but its use seems to increase the risk of postoperative empyema.

A unique congenital mediastinal malformation.

We report a case of a 35-year-old patient presenting with a unique asymptomatic malformation associating extralobar pulmonary sequestration communicating with a bronchogenic cyst of the esophageal wall via the aortopulmonary window, dextroisomerism, and complete agenesia of the left pericardium. Despite computed tomography (CT) scan and magnetic resonance imaging (MRI), the diagnosis could not be established before left thoracotomy. The sequestrated lobe and bronchogenic cyst were then successfully resected.