Cardiovascular risk in adult hypopituitaric patients with growth hormone deficiency: is there a role for vitamin D?

Hypovitaminosis D represent an environmental risk factors for cardiovascular (CV) disease. To investigate the prevalence of hypovitaminosis D and the correlation between GH/IGF-I deficiency and hypovitaminosis D with CV risk in GH deficiency (GHD) patients. A link between these hormones has been shown. Forty-one hypopituitaric patients with GHD (22 males, age 18-84 years) and 41 controls were enrolled in the study. Anthropometric parameters, blood pressure, glucose and lipid profile, parathyroid hormone (PTH), 25(OH) vitamin D (vitamin D), metabolic syndrome (MS), GH peak after GHRH + ARG, IGF-I, and standard deviation score (SDS) of IGF-I (zIGF-I) were assessed. Vitamin D levels were lower in patients than in controls (21.3 ± 12.3 vs. 28.2 ± 9.4, p = 0.006). Deficiency was found in 51 % of patients versus 14.6 % of controls (p < 0.01), insufficiency in 26.8 versus 41.4 % (p = 0.269) and normal vitamin D levels in 21.9 versus 43.9 % (p = 0.060). The prevalence of dyslipidemia was 51.2 % in patients versus 12.1 % in controls (p < 0.001), type 2 diabetes mellitus (DM) was 7.3 versus 17 % (p = 0.292), hypertension was 44 versus 22 % (p = 0.060), and MS was 17 versus 14.6 % (p = 0.957). In patients, an association was found between the presence of hypovitaminosis D and the prevalence of dyslipidemia, hypertension and MS and between zIGF-I and the prevalence of hypertension. Hypovitaminosis D was the most powerful predictor of the prevalence of dyslipidemia and hypertension. GHD patients have an increased prevalence of hypovitaminosis D compared with controls. The presence of hypovitaminosis D was the most powerful predictor of the prevalence of dyslipidemia and hypertension in GHD patients, suggesting the involvement of both factors in the CV risk in these patients

Addressing the Role of Angiogenesis in Patients with Advanced Pancreatic Neuroendocrine Tumors Treated with Everolimus: A Biological Prospective Analysis of Soluble Biomarkers and Clinical Outcomes

Simple Summary Despite the approval of new targeted therapies for pancreatic neuroendocrine tumors (PanNETs) over the past decades, the early identification of resistant tumors remains the major challenge, mainly because clear signs of tumor shrinkage are rarely achieved by imaging assessment. Starting from the hypothesis that angiogenesis can be implicated in the resistance to mTOR inhibitors, we evaluated a specific angiogenesis panel (through the measurement of soluble biomarkers for angiogenesis turnover, circulating endothelial cells, and circulating progenitors) as possible predictors of resistance to everolimus or everolimus efficacy in PanNETs. Our study showed that none of the investigated categories of biomarkers had a predictive value for everolimus resistance or efficacy. However, we suggest that circulating endothelial progenitors might be surrogate biomarkers for angiogenesis activity in PanNETs during everolimus treatment, and their baseline levels might correlate with survival outcomes. These data have never been reported before for NETs. Background: The success of targeted therapies in the treatment of pancreatic neuroendocrine tumors has emphasized the strategy of targeting angiogenesis and the PI3K/AKT/mTOR pathway. However, the major challenge in the targeted era remains the early identification of resistant tumors especially when the efficacy is rarely associated to a clear tumor shrinkage at by imaging assessment. Methods: In this prospective study (NCT02305810) we investigated the predictive and prognostic role of soluble biomarkers of angiogenesis turnover (VEGF, bFGF, VEGFR2, TSP-1) circulating endothelial cells and progenitors, in 43 patients with metastatic panNET receiving everolimus. Results: Among all tested biomarkers, we found a specific subpopulation of circulating cells, CD31+CD140b-, with a significantly increased tumor progression hazard for values less or equal to the first quartile. Conclusion: Our study suggested the evidence that circulating cells might be surrogate biomarkers of angiogenesis activity in patients treated with everolimus and their baseline levels can be correlated with survival. However, further studies are now needed to validate the role of these cells as surrogate markers for the selection of patients to be candidates for antiangiogenic treatments

Nutrition and osteoporosis: preliminary data of campania region of european personalised ict supported service for independent living and active ageing

Background: Bone impairment and malnutrition are associated with significant disability and mortality. PERSSILAA is an European project developing health services to detect and prevent frailty in older adults by addressing cognitive, physical and nutritional. Methods: Subjects underwent anthropometric measurements, calcaneal quantitative ultrasound (QUS) scan and PREDIMED (PREvención con DIetaMEDiterránea) questionnaire. Aim: To investigate the association between adherence to the Mediterranean Diet (MD) and bone health. Results: 87 subjects (4 males and 83 females) 70.1±4.9 aged, were examined. Mean Body Mass Index (BMI) was 28.7±4.7(kg/m2): in particular 28 subjects (32.2%) resulted obese, 42 (48.3%) overweight, and only 17 (19.5%) with normal weight. Mean T score was -1.2±1.2: in particular 13 subjects (14.9%) resulted osteoporotic; 43 (49.5%) osteopenic; and 31 (35.6%) with normal bone mineral density. Regarding adherence to MD, 9 subjects (10.3%) were poorly adherent; 41 (47.2%) average adherent; 37 (42.5%) highly adherent. T-score was associated with PREDIMED score and osteoporotic nsubjects presented the lowest PREDIMED score (5.8±2.2). Conclusions: These preliminary data show a significant correlation between the adherence to the MD and bone health parameters. The association between MD and bone health highlights the potential beneficial effects of nutritional interventions promoting a Mediterranean food pattern, as safe adjuvant treatment in ageing

Pathology reporting in neuroendocrine neoplasms of the digestive system: everything you always wanted to know but were too afraid to ask

During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals

Commentary: Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management

In the issue of March 2021, Lenschow et al. reported the case of a 46-year-old woman with recurrent, programmed death-ligand-1 (PD-L1) negative, tumor mutational burden (TMB)-high parathyroid carcinoma (PC), who showed stable disease as her best response on imaging, and a three-fold drop in PTH after treatment with intravenous pembrolizumab. Given the remarkable results obtained by Lenschow et al. with the anti-PD-1 agent pembrolizumab in the above-mentioned case, we performed an extensive search for possible further relevant data sources, including a) full published articles in international online databases (PubMed, Web of Science, Scopus, and Embase); b) preliminary reports in selected international meeting abstract repositories (American Society of Clinical Oncology, ASCO; European Neuroendocrine Tumor Society, ENET; European Society for Medical Oncology, ESMO); c) registered clinical trials in the U.S. National Institutes of Health registry of clinical trials (http://clinicaltrials.gov) and in any primary register of the WHO International Clinical Trials Registry Platform (ICTRP)

Neoadjuvant Therapy for Neuroendocrine Neoplasms: Recent Progresses and Future Approaches

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors, their treatment being challenging and requiring a multidisciplinary approach. Though the only curative treatment is surgery, up to 50% of patients are diagnosed with metastatic disease. In the last years, neoadjuvant chemo(radio)therapy has become part of the standard of care in the treatment of different cancer types. However, evidence of its efficacy and safety in NEN patients has not yet been confirmed in the literature. The aim of the present review is to perform an extensive review of the scientific evidence for neoadjuvant therapy in patients with gastroenteropancreatic and thoracic NENs

Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions

PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma arising from the skin. We aimed to review and deal with some of the most relevant controversial topics on the correct use of immunotherapy for the treatment of MCC. METHODS: The primary search was carried out via PubMed, EMBASE, and the Cochrane Library (until 31st May, 2018), while other articles and guidelines were retrieved from related papers or those referenced in these papers. Additionally, we performed an extensive search on ClinicalTrials.gov to gather information on the ongoing clinical trials related to this specific topic. RESULTS: We performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies evaluating these issues: Are there any predictive criteria of response to immunotherapy? What is the correct place of immunotherapy in the treatment algorithm of MCC? What is the best choice after immunotherapy failure? What to do with patients for whom immunotherapy is not been feasible or contraindicated? How long should immunotherapy be prolonged, and what follow-up should be offered after complete response? CONCLUSION: The therapeutic landscape of MCC is rapidly evolving: many open issues will probably be resolved, and many other questions are likely to arise in the next few years. The results of ongoing prospective clinical trials and of several other studies on these issues are eagerly awaite

Metronomic chemotherapy in patients with advanced neuroendocrine tumors: A single-center retrospective analysis

Neuroendocrine tumors (NETs) are more commonly slow-growing, therefore patients often receive chronic systemic therapies for tumor growth control and preservation of quality of life. Metronomic chemotherapy (mCT) is in line with this goal as it leads to stabilization of tumor growth over time without severe systemic toxicity. This is a retrospective analysis of patients with metastatic NETs receiving metronomic capecitabine (mCAP) or temozolomide (mTEM), at a NET-referral center. The aims of the study were to explore activity and safety of mCT and relationships between some characteristics of the patient population and clinical outcomes. Among a total of 67 patients with metastatic well or moderately differentiated (W/M-D) NETs, mostly gastroenteropancreatic (GEP) and nonfunctioning, 1.2 years (95% CI: 0.8–1.8) median progression-free survival (mPFS), and 3.0 years (95% CI: 2.3–4.9) median overall survival (mOS) were observed. Disease control rate was 85%. Grade 3 adverse events occurred in 15% of patients in mCAP and 13% in mTEM, and were mostly hematological and gastrointestinal. At univariate and multivariate analysis none of the variables analyzed (treatment regimen, sex, age at diagnosis, site of primary tumor and metastases, number of previous mCT lines, baseline tumor status before mCT, Ki67 value) were significantly correlated to OS and PFS. Our retrospective study suggested that mCAP and mTEM can be active and well tolerated in patients with metastatic W/M-D NETs, irrespective of the primary site, site of metastases, line of treatment and baseline tumor status

Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology

A Retrospective Analysis of the Correlation between Functional Imaging and Clinical Outcomes in Grade 3 Neuroendocrine Tumors (NETs G3)

Grade 3 (G3) neuroendocrine tumors (NETs) are a novel category among digestive neuroendocrine neoplasms, characterized by Ki-67 &gt;20% and a well-differentiated morphology, presenting high intra-tumor heterogeneity. We aimed to explore the role of dual-tracer PET imaging (68Gallium (Ga)-DOTATOC and 18Fluorodeoxyglucose (FDG)) as overall survival (OS) predictor in NET G3 patients. We performed a retrospective analysis in NET G3 patients treated at our institution between 2003 and 2021. Accordingly, 30 NET G3 patients were analyzed. 68Ga-DOTA-TOC and 18F-FDG uptake were assessed by tumor/non-tumor (T-nonT) ratio. We reported a slightly better OS for patients with &ge;75% concordance between 68Ga-DOTA-TOC and 18F-FDG PET/CT (p = 0.42). Among patients with discordant functional imaging, we reported a better 5-y OS rate for patients with a prevalent 68Ga-DOTATOC vs. 18F-FDG PET/CT (p = 0.016). In positive 18F-FDG PET/CT cases, we reported a better OS for &lt;4 vs. &ge;4 T/non-T ratio (p = 0.021). Among upfront-NET G3 patients with concordant exams, 5-y OS rate was 83.3% (95% CI: 27.3&ndash;97.5). Among patients with discordant exams, 5-y OS rate was 81.3% (52.5&ndash;93.5), 100% for those with prevalent receptor expression, and 50% (11.1&ndash;80.4) for those with prevalent 18F-FDG uptake. Our findings suggest that dual-tracer PET/CT can be considered as a predictor of patient outcome, able to stratify NET G3 patients with poorer prognosis