Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation

The lung Large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensy to metastasize and very poor prognosis. We report an atypical presentation of lung large-cell neuroendocrine carcinoma was diagnosed from a metastatic nodule on the breast. Our patient is a 59 years-old woman that presented in March 2014 non productive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and a lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment

Long-term monitoring reveals forest tree community change driven by atmospheric sulphate pollution and contemporary climate change

Diversity and Distributions published by John Wiley & Sons Ltd Aim: Montane environments are sentinels of global change, providing unique opportunities to assess impacts on species diversity. Multiple anthropogenic stressors such as climate change and atmospheric pollution may act concurrently or synergistically in restructuring communities. Thus, a major challenge for conservation is untangling the relative importance of different stressors. Here, we combine long-term monitoring with multivariate community modelling to estimate the anthropogenic drivers shaping forest tree diversity along an elevational gradient. Location: Camels Hump Mountain, Vermont, USA. Methods: We used Generalized Dissimilarity Modelling (GDM) to model spatial and temporal turnover in beta diversity along an elevational gradient over a 50-year period and tested for spatiotemporal shifts in density and elevational distribution of individual species. GDMs were used to predict community turnover as nonlinear functions of changes in elevation, climate and atmospheric pollution. Results: We observed significant shifts in elevational range and density of individual species, which contributed to an overall reduction in the elevational gradient in beta diversity through time. GDMs showed the combined effects of sulphate deposition and temperature as drivers of this temporal reduction in beta diversity. Spatiotemporal changes differed among species, with shifts observed both up- and downslope. For example, in a reversal of a previous upslope range contraction, red spruce (Picea rubens Sarg.) increased in density and shifted downslope since the 1990s, occupying warmer, drier climates. Main conclusion: Our results demonstrate that global change is impacting the stratification of forest tree diversity along elevational gradients, but the responses of individual species are complex and variable in direction. We suggest abiotic drivers may directly impact individual species while also indirectly altering species interactions along elevational gradients. Our approach modelling the drivers of compositional turnover quantifies the rate and amount of change in beta diversity along environmental gradients and serves as a powerful complement to studying species-specific responses

Natural History and Management of Familial Paraganglioma Syndrome Type 1: Long-Term Data from a Large Family

Head and neck paragangliomas are the most common clinical features of familial paraganglioma syndrome type 1 caused by succinate dehydrogenase complex subunit D (SDHD) mutation. The clinical management of this syndrome is still unclear. In this study we propose a diagnostic algorithm for SDHD mutation carriers based on our family case series and literature review. After genetic diagnosis, first evaluation should include biochemical examination and whole-body imaging. In case of lesion detection, nuclear medicine examination is required for staging and tumor characterization. The study summarizes the diagnostic accuracy of different functional imaging techniques in SDHD mutation carriers. 18F-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)-computed tomography (CT) is considered the gold standard. If it is not available, 123I-Metaiodobenzylguanidine (MIBG) could be used also for predicting response to radiometabolic therapy. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET-CT has a prognostic role since high uptake identifies more aggressive cases. Finally, 68Ga-peptides PET-CT is a promising diagnostic technique, demonstrating the best diagnostic accuracy in our and in other published case series, even if this finding still needs to be confirmed in larger studies. Periodic follow-up should consist of annual biochemical and ultrasonographic screening and biannual magnetic resonance examination to identify biochemical silent tumors early

Capecitabine and Temozolomide (CAPTEM) in advanced neuroendocrine neoplasms (NENs): a systematic review and pooled analysis

Background Retrospective studies and single center experiences suggest a role of capecitabine combined with temozolomide (CAPTEM) in neuroendocrine tumors (NENs). Methods We performed a systematic review to assess the efficacy and safety of CAPTEM in patients affected with NENs, with the aim to better clarify the role of this regimen in the therapeutic algorithm of NENs. Results A total of 42 articles and 1818 patients were included in our review. The overall disease control rate was 77% (range 43.5%-100%). The median progression free survival ranged from 4 to 38.5 months, while the median overall survival ranged from 8 to 103 months. Safety analysis showed an occurrence of G3-G4 toxicities in 16.4% of the entire population. The most common toxicities were hematological (27.2%), gastrointestinal (8.3%,) and cutaneous (3.2%). Conclusion This systematic review demonstrated that CAPTEM was an effective and relatively safe treatment for patients with advanced well-moderate differentiated NENs of gastroenteropancreatic, lung and unknown origin

Exenatide as an Adjunct to Nicotine Patch for Smoking Cessation and Prevention of Postcessation Weight Gain Among Treatment-Seeking Smokers With Pre-Diabetes and/or Overweight: Study Protocol for a Randomised, Placebo-Controlled Clinical Trial

INTRODUCTION: Obesity and smoking are the two leading causes of preventable death in the USA. Unfortunately, most smokers gain weight after quitting. Postcessation weight gain (PCWG) is frequently cited as one of the primary barriers to a quit attempt and a common cause of relapse. Further, excessive PCWG may contribute to the onset or progression of metabolic conditions, such as hyperglycaemia and obesity. The efficacy of the current treatments for smoking cessation is modest, and these treatments have no clinically meaningful impact on mitigating PCWG. Here, we outline a novel approach using glucagon-like peptide 1 receptor agonists (GLP-1RA), which have demonstrated efficacy in reducing both food and nicotine intake. This report describes the design of a double-blind, placebo-controlled, randomised clinical trial that evaluates the effects of the GLP-1RA exenatide as an adjunct to nicotine patches on smoking abstinence and PCWG. METHODS AND ANALYSIS: The study will be conducted at two university-affiliated research sites in Houston, Texas, the UTHealth Center for Neurobehavioral Research on Addiction and Baylor College of Medicine Michael E. DeBakey VA Medical Centre. The sample will consist of 216 treatment-seeking smokers with pre-diabetes (haemoglobin A1c of 5.7%-6.4%) and/or overweight (body mass index of 25 kg/m ETHICS AND DISSEMINATION: The study has been approved by the UTHealth Committee for the Protection of Human Subjects (HSC-MS-21-0639) and Baylor College of Medicine Institutional Review Board (H-50543). All participants will sign informed consent. The study results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05610800

KPNB1 (karyopherin (importin) beta 1)

Review on KPNB1 (karyopherin (importin) beta 1), with data on DNA, on the protein encoded, and where the gene is implicated

Angioside: The role of Angiogenesis and Hypoxia in Lung Neuroendocrine Tumours According to Primary Tumour Location in Left or Right Parenchyma

Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypical (AC) carcinoids, represent 30% of NETs. Angiogenesis plays an essential role in NET development and progression. A higher vascular network is a marker of differentiation, with positive prognostic implications. Materials and Methods: We retrospectively evaluated microvessel density (MVD) by CD34 immunohistochemical (IHC) staining and hypoxia by IHC staining for Hypoxia-inducible factor 1α (HIF-1α), comparing right- and left-lung parenchyma in 53 lung NETs. Results: The median age was 66 years (39–81), 56.6% males, 24.5% AC, 40.5% left-sided tumours and 69.8% TNM stage I. The mitotic count was <2/10 per 10 HPF in 79.2%, and the absence of necrosis in 81.1%, 39.6% with Ki67, was ≤2%. The MVD, the number of vessels and the average vessel area median values were significantly higher in the right than the left parenchyma (p: 0.025, p: 0.019, p: 0.016, respectively). Hypoxia resulted present in 14/19 (73.6%) left tumours and in 10/20 (50%) right tumours in the parenchyma (p: 0.129). Conclusions: This study suggests a biological rationale for a different angiogenesis and hypoxia according to the Lu-NETs’ location. In our study, left primary tumours were less vascularized and most likely to present hypoxia than right primary tumours. This finding could have potentially useful prognostic and predictive implications for Lu-NETs

Now you see it, now you don't: star formation truncation precedes the loss of molecular gas by 100 Myr in massive poststarburst galaxies at z ~ 0.6

Interstellar matter and star formatio