Characterization,Prognosis, and Treatment of Patients With Metastatic Lung Carcinoid Tumors

IntroductionMetastatic lung carcinoids (MLCs) remain poorly characterized and no prognostic stratification exists.MethodsWe conducted a retrospective study including patients with MLCs in two European expert centers. The aims were to characterize these cases and to identify prognostic factors of survival and effectiveness of their treatments.ResultsA total of 162 patients with MLC were included: 50% were women, and the median age was 61 years. Half of the patients had synchronous metastases, mainly located in the liver (75%), bone (42%), and lung (25%). According to WHO classification, MLCs were typical (28%), atypical (60%), or unspecified (12%). A functioning syndrome was observed in 43% of cases and an uptake at somatostatin receptor scintigraphy in 76% of cases. The 5-year overall survival rate was 60% and at 10 years this was 25%. In multivariate analysis, Eastern Cooperative Oncology Group performance status of 0-1 (hazard ratio [HR]: 5.81, 95% confidence interval [CI]: 2.10–16.11), uptake on SRS (HR: 0.38, 95% CI: 0.22–0.66), low serum chromogranin A (HR: 2.27, 95% CI: 1.36–3.81), and typical carcinoid (HR: 1.87, 95% CI: 1.26–2.78) were associated with better survival. According to Response Evaluation Criteria in Solid Tumors version 1.0, the highest objective response rates were obtained after radiofrequency ablation of metastases (86%), liver embolization (56%), peptide receptor radionuclide therapy (27%), and oxaliplatin-based chemotherapy (18%).ConclusionsMLCs are characterized by a high frequency of atypical carcinoids, functioning syndrome, and liver/bone metastases. WHO classification, performance status, somatostatin receptor scintigraphy, and chromogranin A were associated with longer survival. Partial response was more frequent with locoregional therapies, peptide receptor radionuclide therapy, or oxaliplatin-based chemotherapy.     

An analysis of communication in conversation in patients with dementia

Patients with degenerative dementia often show language disorders, but little is known about their verbal (VC) and non-verbal communication (NVC). Our aim was to analyse VC and NVC in patients with standard criteria of mild-moderately severe dementia (MMSE ≥ 14/30) resulting from Alzheimer's disease (AD; 29 cases), behavioural variant of frontotemporal dementia (FTD; 16), or dementia with Lewy bodies (DLB; 13). We used the Lille Communication Test, which addresses three domains: participation in communication (PC: greeting, attention, participation), VC (verbal comprehension, speech outflow, intelligibility, word production, syntax, verbal pragmatics and verbal feedback), and NVC (understanding gestures, affective expressivity, producing gestures, pragmatics and feedback). Patients were compared with 47 matching control subjects. AD patients were partially impaired (p ≤ 0.01) in PC (greeting), and more definitely in VC, especially by verbal comprehension and word finding difficulties and to a much lesser degree in verbal pragmatics (responding to open questions, presenting new information), while NVC was mostly preserved. FTD patients were severely impaired in PC. VC difficulties were related to lexical-semantic, syntactic and more specifically pragmatic problems. NVC was impaired by difficulties in affective expressivity, pragmatics and feedback management. DLB patients showed modest difficulties with VC. PC, VC and NVC strongly correlated with performance in the dementia rating scale. In conclusion, the profile of communication difficulties was quite different between groups. FTD patients showed most severe difficulties in PC and verbal and non-verbal pragmatics, in relation to their frontal lesions. AD patients had prominent impairment of lexical-semantic operations.     

Subtype analysis of Blastocystis isolates from symptomatic patients in Egypt

Blastocystis sp. has been described as the most common intestinal parasite in humans and has an increased impact in public health. To improve our understanding of the molecular epidemiology of this human-emerging parasite, we determined the Blastocystis subtypes (STs) and their relative frequency in Egyptian patients living in or in the vicinity of Cairo and presenting gastrointestinal symptoms. We obtained a total of 20 stool samples identified as positive for Blastocystis by microscopic examination of smears. Genotyping using partial small subunit ribosomal RNA gene analysis identified a total of 21 Blastocystis isolates corresponding to 19 single infections and one mixed infection (ST1 and ST3). Three STs were identified: ST3 was the most common ST in the present Egyptian population (61.90%) followed by ST1 (19.05%) and ST2 (19.05%). Together with previous studies carried out in different areas in Egypt, a total of five STs (ST1, ST2, ST3, ST4, and ST6) have been found in symptomatic patients. These data were compared to those available in the literature, and we underlined variations observed in the number and relative proportions of STs between and within countries. On the whole, it seemed that Blastocystis infection is likely not associated with specific STs even if some STs are predominant in the epidemiologic studies, but rather with a conjunction of factors in the course of infection including environmental risk and parasite and host factors.     

A new organotypic model containing dermal-type macrophages

Human skin equivalents (SEs) are popular three-dimensional (D) cell culture systems in fundamental and applied dermatology. They have been made to contain dendritic cells, but so far no study on the incorporation of potentially anti-inflammatory dermal macrophages has been performed. Here, we show that monocyte-derived dermal-type macrophages can be introduced into a rigid scaffold with dermal fibroblasts. They maintain their cell surface markers CD163, DC-SIGN/CD209 and HLA-DR, which discriminate them from monocytes and dendritic cells. They retain the ability to produce the anti-inflammatory cytokine IL-10 in response to lipopolysaccharide (LPS) and to phagocytose latex beads. We thus demonstrate the feasibility of creating macrophage-fibroblast 3D cultures as a first step towards generating SEs with dermal macrophages.     

A new luciferase-based quantitative assay for the evaluation of human trophoblast fusion

The syncytiotrophoblast is a multinuclear cell layer maintained through fusion events with cytotrophoblasts and plays a key role in the properties of the placenta. Monitoring fusion in this cell layer is important in studies aimed at understanding its function. We herein propose a new fusion assay based on the transactivating potential of the human immunodeficiency virus type 1 (HIV-1) Tat protein on its promoter present in the long terminal repeat (LTR) region. We used 2 BeWo cell populations, one stably transfected with the HIV-1 LTR positioned upstream of the luciferase gene and the other stably transfected with a Tat expression vector. Both stable cell lines were responsive to Tat-mediated LTR transactivation and demonstrated normal fusion and human chorionic gonadotropin (hCG) secretion upon stimulation. When both BeWo cell lines were cocultured, forskolin-mediated induction of fusion led to an increase in luciferase activity, which was sensitive to anti-syncytin 1 and -2 antibodies and syncytin 2 small interfering RNAs (siRNAs). Similar results were obtained in primary trophoblasts. Our results highlight the effectiveness and accuracy of this new quantification assay for trophoblast fusion.     

Cancer médullaire de la thyroïde (CMT) de l'enfant

Medullary thyroid carcinoma (MTC) is rare in children. MTC is almost always inherited and occurs as part of a multiple endocrine neoplasia type 2A and B, due to germline mutation in the RET proto-oncogene. MTC in the pediatric population is most often diagnosed in the course of a familial genetic investigation. But when the child is the proband, a de novo mutation is most often founded. The main aim is to treat MTC before extrathyroidal extension occurs because when distant metastases are present, it is rarely curable. Treatment is based on total thyroidectomy with cervical lymph node dissection.