Necrosis- and apoptosis-related Met cleavages have divergent functional consequences.

Upon activation by its ligand hepatocyte growth factor/scatter factor, the receptor tyrosine kinase Met promotes survival, proliferation, and migration of epithelial cells during embryogenesis. Deregulated Met signaling can also promote cancer progression and metastasis. Met belongs to the functional family of dependence receptors whose activity switches from pro-survival to pro-apoptotic during apoptosis upon caspase cleavage. Although apoptosis resistance is a hallmark of cancer cells, some remain sensitive to other cell death processes, including necrosis induced by calcium stress. The role and fate of Met during necrotic cell death are unknown. Following treatment with calcium ionophores, cell lines and primary cells undergo necrosis, and the full-length Met receptor is efficiently degraded. This degradation is achieved by double cleavage of Met in its extracellular domain by a metalloprotease of the A disintegrin and metalloproteinase (ADAM) family and in its intracellular domain by calpains (calcium-dependent proteases). These cleavages separate the Met extracellular region from its kinase domain, thus preventing Met activity and its potential pro-survival activity. Although the intracellular fragment is very similar to the fragment generated by caspases, it displays no pro-apoptotic property, likely because of the presence of the last few amino acids of Met, known to inhibit this pro-apoptotic function. The fragments identified here are observed in lung tumors overexpressing the Met receptor, along with fragments previously identified, suggesting that proteolytic cleavages of Met are involved in its degradation in tumor tissues. Thus, Met is a modulator of necrosis, able to protect cells when activated by its ligand but efficiently degraded by proteolysis when this process is engaged.

Morphologic characterization of isolated bovine early preantral follicles during short-term individual in vitro culture.

To provide new insights in the molecular mechanism controlling preantral follicular development and to unravel the needs to support in vitro follicular development of early-stage preantral follicles (PAFs), there is a need for alternative in vitro bovine follicle culture methods. In this study, we aimed to characterize follicular dynamics using an IVC system of isolated and individually cultured bovine early PAFs during 10 days to generate individual follicle follow-up data. Preantral follicles (<50 µm) were isolated from slaughterhouse ovaries and cultured individually for 10 days. Individual follicle morphology, growth, survival, quality, and cell proliferation were evaluated in time by combining noninvasive and invasive assessment methods. The PAFs were light microscopically evaluated during culture to assess follicular dynamics, stained with neutral red to determine follicle viability, stained with 4',6-diamidino-2-phenylindole and terminal deoxynucleotidyl transferase dUTP nick end labeling to evaluate cell proliferation and follicle quality, and processed for histologic evaluation to assess follicle morphology. On the basis of their morphology, follicles were subdivided in three categories, with category 1 follicles showing the best morphologic features. On Day 0, only category 1 follicles were selected, but follicle categories were reassigned on evaluation Days 1, 2, 4, 7, or 10. Although 67% of the follicles survived 10 days of IVC, the number of follicles exhibiting a normal morphology decreased significantly from Day 7 onward and the apoptotic index increased significantly from Day 10. Both category 1 and 2 follicles showed a significant increase in follicular diameter (Day 10: 21.80 ± 0.86 and 11.82 ± 0.80, respectively). This increase in follicular diameter showed to be correlated with an increase in the total cell number. In conclusion, this culture system showed to support follicular development until Day 10, although the proportion of follicles showing normal morphologic features and the follicular quality decreased after 10 days of IVC. Follicles maintaining their category 1 morphologic features over time seem to be of a better quality and show a higher developmental competence as compared to category 2 and 3 follicles.

[Chamberlain biopsy is not necessary when mature teratoma is evident on imagery]. / Un Chamberlain inutile devant un tératome mature évident à l'imagerie.

INTRODUCTION: Mature teratoma represents 60 % of germinal cells tumours of the mediastinum. Most patients with these tumours are asymptomatic, so the neoplasms are usually discovered by accident during routine chest X-ray examination. They have specific and almost pathognomonic radiological features. However, patients can be symptomatic and may present with chest, back, or shoulder pain; dyspnoea; fever; pleural effusion; cough; and bulging of the chest wall. CASE REPORT: We report the case of a young woman presenting with a giant mediastinal mature teratoma compressing the left lung. The patient was admitted for dyspnoea and non productive cough. The chest X-ray showed a mediastinal mass and a chest computed tomography scan revealed a heterogeneous pluritissular mass lesion of the mediastinum. Complete surgical removal is the treatment of choice for mature cystic teratomas, with optimal results and an acceptable surgical risk. This approach allows confirmation of the diagnosis and is the only way to rule out the presence of malignancy. Surgical biopsy by the Chamberlain method is therefore not strictly necessary. DISCUSSION: When chest X-ray and a computed tomography scan show specific radiological features of teratoma, a complete resection should be undertaken if the patient is fit for surgery. This will confirm the anatomico-pathological diagnosis, exclude the presence of malignant cells and it represents the treatment of choice of mature teratomas.

[Anti-Hu antibody syndrome: diagnostic and therapeutic difficulties]. / Syndrome des anticorps anti-Hu: difficultés diagnostiques et thérapeutiques.

INTRODUCTION: Anti-Hu antibody syndrome is a paraneoplastic syndrome usually associated with small cell lung carcinoma which induces various symptoms, particularly neurological ones. CASE REPORT: We describe the case of a 49-year old woman with a small cell lung carcinoma who initially experiences a spontaneous regression but then developed neurological symptoms associated with severe autonomic dysfunction manifesting as chronic intestinal pseudo-obstruction and leading finally to hemodynamic failure. CONCLUSION: Anti-Hu antibody syndrome remains a rare entity. Its diagnosis must be considered in the face of neurologic symptoms associated with small cell lung cancer.

[Pleuro-pulmonary metastases from a malignant mesothelioma of the tunica vaginalis]. / Métastases pleuropulmonaires d'un mésothéliome de la vaginale testiculaire.

INTRODUCTION: Mesothelioma is a malignant tumour of the serous membranes that principally affects the pleura. Peritoneal, pericardial and tunica vaginalis mesothelioma are very rare. CASE REPORT: We report the case of a 65-year-old male with malignant mesothelioma of the tunica vaginalis (MTV). He presented with several local recurrences and, five years after the initial surgery, with pulmonary nodules and a pleural effusion. Pleural biopsies confirmed epithelioid mesothelioma. A diagnosis of pleuro-pulmonary metastases from previous malignant MTV was made. CONCLUSIONS: Malignant MTV is a rare and aggressive tumor with frequent local recurrences and, rarely, visceral metastases. This case report emphasizes the difficulties of the differential diagnosis between pleural mesothelioma and pleural metastases from MTV. The lack of any treatment for metastatic malignant MTV is discussed.

[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.

Giant Primary Liposarcoma of the Thoracic Esophagus

Primary liposarcomas of the mediastinum are unusual tumors. We report herein a case of a 64 year-old man; who presented a liposarcoma involving the mediastinum and the neck. A complete resection was performed and we had a free-disease survival result of eighteen months

Extinction-ratio-independent method for chirp measurements of Mach-Zehnder modulators.

The authors describe a general method to extract the frequency chirping of Mach-Zehnder modulators based on direct measurements of the output spectrum. This method is independent of the modulator extinction ratio and allows measurement of the intrinsic chirp parameter to an accuracy of 5%.

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.

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.

Resection of adrenal metastases from non-small cell lung cancer: a multicenter study.

BACKGROUND: In recent case reports and limited series, adrenalectomy was recommended for an isolated adrenal metastasis from non-small cell lung cancer (NSCLC). METHODS: We retrospectively studied patients with a solitary adrenal metastasis from NSCLC who had undergone potentially curative resection in eight centers. RESULTS: Forty-three patients were included. Their adrenal gland metastasis was discovered synchronously with NSCLC in 32 patients, and metachronously in 11. It was homolateral to the NSCLC in 31 patients and contralateral in 12 (p < 0.01). Median survival was 11 months, and 3 patients survived more than 5 years. There was no difference between the synchronous and metachronous groups regarding recurrence rate or survival. Survival was not affected by the homolateral location of the metastasis, the histology of the NSCLC, TNM stage, any adjuvant and neoadjuvant treatment, or, in the metachronous group, a disease-free interval exceeding 6 months. CONCLUSIONS: We confirm the possibility of long-term survival after resection of isolated adrenal metastasis from NSCLC, but no clinical or pathologic criteria were detected to identify patients amenable to potential cure.

Mucinous bronchioloalveolar carcinomas display a specific pattern of mucin gene expression among primary lung adenocarcinomas.

Lung adenocarcinomas are heterogeneous clinically and histologically. Expression of the mucin genes was analyzed as a molecular marker of glandular cytodifferentiation in primary lung adenocarcinomas. Expression was correlated with histopathologic subtypes of World Health Organization classification with the aim of investigating the histogenesis of primary lung adenocarcinomas. Thirty-four primary lung adenocarcinomas were examined by in situ hybridization for mucin gene expression (MUC1-4, MUC5AC, MUC5B, MUC6-7) and by immunohistochemistry for MUC5AC and MUC5B apomucin expression. Mucinous bronchioloalveolar carcinoma (BAC) had a homogeneous pattern of mucin gene expression different from those of other types of lung adenocarcinoma, involving secreted mucins (MUC5AC, MUC5B, and MUC6) and membrane-bound mucins (MUC1, MUC3, and MUC4). Non-BAC adenocarcinoma and mucinous BAC aberrantly expressed mucin genes MUC3, and MUC3 and MUC6, respectively, which are undetectable in normal fetal and adult lung. Our results show the particular phenotype of mucin gene expression in mucinous type of BACs and the heterogeneous expression of respiratory and nonrespiratory mucins in the other types. This finding supports the theory of a common progenitor cell with the potential of multicellular differentiation. From a practical point of view, the aberrant expression of MUC3 and MUC6 could serve as a diagnostic marker in the management of the mucinous type of bronchioloalveolar carcinomas. HUM PATHOL 32:274-281.

Chemokine-induced cutaneous inflammatory cell infiltration in a model of Hu-PBMC-SCID mice grafted with human skin.

Recently, certain chemokines and chemokine receptors have been preferentially associated with the selective recruitment in vitro of type 1 T cells, such as IP-10 and its receptor CXCR3, or type 2 T cells such as monocyte-derived chemokine (MDC) and eotaxin and their receptors CCR4 and CCR3. Very few models have provided confirmation of these findings in vivo. Taking advantage of the humanized SCID mouse model grafted with autologous human skin, the ability of the chemokines IP-10, MDC, eotaxin, and RANTES to stimulate cell recruitment was investigated. Intradermal IP-10 injection resulted in an influx of CD4+ T lymphocytes but also surprisingly in the recruitment of dendritic cells. MDC recruited mainly CD8+ T lymphocytes, and had little effect on eosinophils. As predicted, eotaxin was a potent inducer of eosinophil and basophil migration, also recruiting CD4+ T cells. RANTES, a ubiquitous chemokine associated with both type 1 and type 2 profiles, was able to recruit all cell types. CXCR3-positive cells were preferentially recruited by IP-10, whereas CCR3- and CCR4-positive cells were predominantly found after injection of eotaxin and MDC. Thus, in a human environment in vivo, some chemokines have the ability to recruit cells expressing chemokine receptors preferentially expressed on type 1 or type 2 cells. Further investigations revealed that MDC and eotaxin induced the recruitment of type 2, but not type 1, cytokine-producing cells. RANTES, on the other hand, induced the migration of both type 1 and type 2 cytokine-secreting cells, whereas IP-10 did not induce the recruitment of either subtype. These studies provide detailed information on the properties of MDC, eotaxin, IP-10, and RANTES as chemotactic molecules in skin in vivo. The use of the humanized SCID mouse model grafted with human skin is validated as a useful model for the evaluation of chemokine function in the inflammatory reaction, and suggests that therapeutic targeting of certain chemokines might be of interest in diseases associated preferentially with a type 1 or type 2 profile.