A Critical Appraisal of Contemporary and Novel Biomarkers in Pheochromocytomas and Adrenocortical Tumors.

Pheochromocytomas/Paragangliomas (PPGLs) and adrenocortical tumors are rare neoplasms with significant heterogeneity in their biologic and clinical behavior. Current diagnostic and predictive biomarkers include hormone secretion, as well as histopathological and genetic features. PPGL diagnosis is based on biochemical measurement of catecholamines/metanephrines, while histopathological scoring systems have been proposed to predict the risk of malignancy.

De-epithelialized Skin Flaps to Minimize Complications in Large Breast Reconstruction: A Tailored Approach.

Mastectomy and immediate reconstruction may be challenging in patients with large breasts, especially when significant ptosis is also present. Skin-reducing mastectomy (SRM) is usually indicated in these cases, although with increased morbidity. The aims of the study were to introduce 2 modifications of the classic technique and to incorporate them in the management algorithm to improve the outcomes.

Intermittent Energy Restriction, Weight Loss and Cardiometabolic Risk: A Critical Appraisal of Evidence in Humans.

Dietary patterns with intermittent energy restriction (IER) have been proposed as an attractive alternative to continuous energy restriction (CER) for the management of obesity and its associated comorbidities. The most widely studied regimens of IER comprise energy restriction on two days per week (5:2), alternate-day energy restriction by 60-70% (ADF), and timely restriction of energy intake during a specific time window within the day (TRF; time-restricted feeding). Although there is some evidence to suggest that IER can exert beneficial effects on human cardiometabolic health, yet is apparently not superior compared to CER, there are still some critical issues/questions that warrant further investigation: (i) high-quality robust scientific evidence regarding the long-term effects of IER (safety, efficacy, compliance) is limited since the vast majority of intervention studies had a duration of less than 6 months; (ii) whether the positive effects of IER are independent of or actually mediated by weight loss remains elusive; (iii) it remains unknown whether IER protocols are a safe recommendation for the general population; (iv) data concerning the impact of IER on ectopic fat stores, fat-free mass, insulin resistance and metabolic flexibility are inconclusive; (v) the cost-effectiveness of IER dietary regimens has not been adequately addressed; (vi) direct head-to-head studies comparing different IER patterns with variable macronutrient composition in terms of safety and efficacy are scarce; and (vii) evidence is limited with regard to the efficacy of IER in specific populations, including males, the elderly and patients with morbid obesity and diabetes mellitus.

Changing biological behaviour of NETs during the evolution of the disease: progress on progression.

Following improvements in the management and outcome of neuroendocrine neoplasms (NENs) in recent years, we see a subset, particularly of pancreatic NENs, which become more aggressive during the course of the disease. This is reflected by an increase in the Ki-67 labelling index, as a marker of proliferation, which may lead to an occasion of increase in grading, but generally does not appear to be correlated with histologically confirmed dedifferentiation. A systematic review of the literature was performed in PubMed, Cochrane Library, and Embase until May 2020 to identify cases that have behaved in such a manner.

Non-coding RNAs (miRNAs and lncRNAs) and their roles in lymphogenesis in all types of lymphomas and lymphoid malignancies.

Contemporary developments in molecular biology have been combined with discoveries on the analysis of the role of all non-coding RNAs (ncRNAs) in human diseases, particularly in cancer, by examining their roles in cells. Currently, included among these common types of cancer, are all the lymphomas and lymphoid malignancies, which represent a diverse group of neoplasms and malignant disorders. Initial data suggest that non-coding RNAs, particularly long ncRNAs (lncRNAs), play key roles in oncogenesis and that lncRNA-mediated biology is an important key pathway to cancer progression.

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) ≤2 cm: Study Protocol for a Prospective Observational Study.

The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available.

Managing Ipilimumab-Induced Hypophysitis: Challenges and Current Therapeutic Strategies.

Over the past years, progress has been made in cancer immunotherapy following the development of immune checkpoint inhibitors (ICI) that have been proved effective in the management of many malignancies. Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4), has been approved for the treatment of advanced melanoma but has been associated with the development of several endocrine immune-related adverse events (irAEs). Hypophysitis is the most common endocrine irAE related to ipilimumab with a reported incidence ranging from 1.

Diabetes distress is associated with individualized glycemic control in adults with type 2 diabetes mellitus.

Purpose: It has been proposed that the negative emotional state of diabetes distress (DD) may exert a detrimental effect on glycemic outcomes of individuals struggling with diabetes-related challenges. Thus far, no study has investigated this association by utilizing individualized treatment targets of patients' glycemic control. Therefore, we sought to identify the potential role of DD in the achievement of individualized glycemic targets (AIGTs) among persons with type 2 diabetes mellitus (T2D).

Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy.

The circadian rhythm derives from the integration of many signals that shape the expression of clock-related genes in a 24-h cycle. Biological tasks, including cell proliferation, differentiation, energy storage, and immune regulation, are preferentially confined to specific periods. A gating system, supervised by the central and peripheral clocks, coordinates the endogenous and exogenous signals and prepares for transition to activities confined to periods of light or darkness.

Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study.

The purpose of this study was to explore the efficacy and safety of everolimus administered as a first-line treatment in newly diagnosed patients with metastatic or inoperable gastroenteropancreatic neuroendocrine tumors (GEP NETs). This phase II, multicenter, single-arm study included patients with well-differentiated GEP NETs and a Ki67 < 20%. Everolimus, at 10 mg/day, was administered until disease progression; 18 patients (72%) concomitantly received octreotide long-acting release (LAR), at 30 mg/month.

Expression of clock-related genes in benign and malignant adrenal tumors.

Although the effect of the central clock system on adrenal function has been extensively studied, the role of the peripheral clock system in adrenal tumorigenesis remains largely unexplored. In this study we investigated the expression of clock-related genes in normal adrenocortical tissue and adrenocortical tumors. Twenty-seven fresh frozen human adrenal tissues including 13 cortisol secreting adenomas (CSA), seven aldosterone producing adenomas (APA), and seven adrenocortical carcinomas (ACC) were collected.

Hypophysitis (Including IgG4 and Immunotherapy).

Hypophysitis is characterized by inflammation of the pituitary gland that can be primary (PH) or secondary (SH) to other diseases or following drug administration. It may also be classified according to anatomical and histopathological criteria, leading to variable degrees of hypopituitarism and/or compressive symptoms to nearby structures. There has recently been an increase in the number of hypophysitis cases, raising the interest on the spectrum of its pathogenesis, clinical, biochemical/endocrinological, and imaging features.

Dealing With Burn Patients in War Zones.

Objective: Treating burn patients in the battlefield is one of the biggest challenges that military doctors and medical personnel can face. Wound patterns have been changed over time due to the introduction of new weapons, and many different aspects play a major role in the management of those burns nowadays. There is a potential gap in care of burn patients in war zones.

Important Considerations for the Treatment of Patients with Diabetes Mellitus and Heart Failure from a Diabetologist's Perspective: Lessons Learned from Cardiovascular Outcome Trials.

Heart failure (HF) represents an important cardiovascular complication of type 2 diabetes mellitus (T2DM) associated with substantial morbidity and mortality, and is emphasized in recent cardiovascular outcome trials (CVOTs) as a critical outcome for patients with T2DM. Treatment of T2DM in patients with HF can be challenging, considering that these patients are usually elderly, frail and have extensive comorbidities, most importantly chronic kidney disease. The complexity of medical regimens, the high risk clinical characteristics of patients and the potential of HF therapies to interfere with glucose metabolism, and conversely the emerging potential of some antidiabetic agents to modulate HF outcomes, are only some of the challenges that need to be addressed in the framework of a team-based personalized approach.

Neoplastic metastases to the endocrine glands.

Endocrine organs are metastatic targets for several primary cancers, either through direct extension from nearby tumour cells or dissemination via the venous, arterial and lymphatic routes. Although any endocrine tissue can be affected, most clinically relevant metastases involve the pituitary and adrenal glands with the commonest manifestations being diabetes insipidus and adrenal insufficiency respectively. The most common primary tumours metastasing to the adrenals include melanomas, breast and lung carcinomas, which may lead to adrenal insufficiency in the presence of bilateral adrenal involvement.

Differential Expression of Apoptotic and Low-Grade Inflammatory Markers in Alzheimer Disease Compared to Diabetes Mellitus Type 1 and 2.

Background: Neuroinflammation, impaired brain insulin signaling, and neuronal apoptosis may be interrelated in the pathophysiology of people with Alzheimer disease (AD) and diabetes, either type 1 or 2 diabetes (T1D or T2D, respectively).

Methods: We studied 116 patients: 41 with AD, 20 with T1D, 21 with T2D, and 34 healthy controls. The number (n) of cytokine-secreting peripheral blood mononuclear cells (PBMCs) before and after mitogenic stimulation was determined for interleukin 1β (IL1β), interleukin 6 (IL6), tumor necrosis factor (TNF) by the enzyme-linked-immuno-spot assay.

Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives.

: Aortic-to-brachial pulse pressure (PP) amplification is a novel biomarker that prognosticates the cardiovascular risk above and beyond central aortic and brachial blood pressure. This phenomenon is modulated by left ventricular contractility and chronotrophy, large-artery stiffness and reflecting properties of microcirculation. However, the relative importance of these parameters as hemodynamic determinant of PP amplification remains elusive.

The Medical Therapy of Craniopharyngiomas: The Way Ahead.

Context: Craniopharyngiomas, which are categorized as adamantinomatous (ACPs) or papillary (PCPs), have traditionally been treated with surgery and/or radiotherapy, although when the tumors progress or recur, therapeutic possibilities are very limited. Following recent advances in their molecular pathogenesis, new medical therapeutic options have emerged.

Evidence Acquisition: The search strategy that we selected to identify the appropriate evidence involved the following medical subject headings (MeSH) terms: ("Craniopharyngioma" [MeSH] AND "Craniopharyngioma/drug therapy" [MeSH]) NOT ("review" [Publication Type] OR "review literature as topic" [MeSH Terms] OR "review" [All Fields]) AND ("2009/05/01" [PDat]: "2019/04/28" [PDat]).

Diagnostic and Management Challenges in Vasoactive Intestinal Peptide Secreting Tumors: A Series of 15 Patients.

Objectives: Vasoactive intestinal peptide-secreting tumors (VIPomas) are rare functioning neuroendocrine tumors often characterized by a difficult-to-control secretory syndrome and high potential to develop metastases. We hereby present the characteristics of 15 cases of VIPomas and provide a recent literature review.

Methods: This was a retrospective data analysis of 15 patients with VIPoma from 3 different centers and literature research through PubMed database during the last 10 years.

Current concepts in the diagnosis and management of neuroendocrine neoplasms of unknown primary origin.

Neuroendocrine neoplasms (NENs) of unknown primary origin (UPO-NENs) are advanced neoplasms constituting 11-22% of all NENs that by definition their primary tissue of origin has not been identified with standard diagnostic work-up. Delineating the primary site of origin of UPO-NENs has important implications for selecting the appropriate treatment and overall prognosis. The small bowel, followed by the lung and pancreas are the most prevalent primary sites of origin of UPO-NENs that are uncovered during an extensive and prolonged diagnostic work-up; however, a number of UPO-NENs may still remain occult even after prolonged follow-up.

Clock genes and cancer development in particular in endocrine tissues.

Circadian rhythms at a central and peripheral level are operated by transcriptional/translational feedback loops involving a set of genes called 'clock genes' that have been implicated in the development of several diseases, including malignancies. Dysregulation of the Clock system can influence cancer susceptibility by regulating DNA damage and repair mechanisms, as well as apoptosis. A number of oncogenic pathways can be dysregulated via clock genes' epigenetic alterations, including hypermethylation of clock genes' promoters or variants of clock genes.