Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.

TAMs constitute a large fraction of infiltrating immune cells in melanoma tissues, but their significance for clinical outcomes remains unclear. We explored diverse TAM parameters in clinically relevant primary cutaneous melanoma samples, including density, location, size, and polarization marker expression; in addition, because cytokine production is a hallmark of macrophages function, we measured CCL20, TNF, and VEGFA intracellular cytokines by single-cell multiparametric confocal microscopy. The Kaplan–Meier method was used to analyze correlation with melanoma-specific disease-free survival and overall survival. No significant correlations with clinical parameters were observed for TAM density, morphology, or location. Significantly, higher contents of the intracellular cytokines CCL20, TNF, and VEGFA were quantified in TAMs infiltrating metastasizing compared to non-metastasizing skin primary melanomas (p < 0.001). To mechanistically explore cytokine up-regulation, we performed in vitro studies with melanoma-conditioned macrophages, using RNA-seq to explore involved pathways and specific inhibitors. We show that p53 and NF-κB coregulate CCL20, TNF, and VEGFA in melanoma-conditioned macrophages. These results delineate a clinically relevant pro-oncogenic cytokine profile of TAMs with prognostic significance in primary melanomas and point to the combined therapeutic targeting of NF-kB/p53 pathways to control the deviation of TAMs in melanoma.

Context Hypoparathyroidism is the most frequent complication after total thyroidectomy (PT-hypoPTH). After 1 year, most patients recover parathyroid function; however, the implicated physiologic dynamics remain unknown. Vitamin D deficiency (VDD) is the main cause of secondary hyperparathyroidism. Whether this compensatory hyperparathyroidism could influence parathyroid function recovery (PFR) in the setting of PT-hypoPTH has not been studied. Objective This work aimed to evaluate the effect of preoperative VDD on PFR. Methods A retrospective study was conducted with a prospectively maintained database including patients undergoing a total thyroidectomy between May 2014 and June 2019. Preoperative vitamin D (25(OH)D) less than 20 mg/mL was defined as VDD. Intact PTH less than 14 pg/mL on postoperative day 1 was defined as PT-hypoPTH. Transient PT-hypoPTH displayed PFR within the first year (early recovery: < 30 days; protracted recovery: > 30 days) whereas definite PT-hypoPTH did not. Survival analysis evaluated the effect of preoperative VDD on PFR, and a binary logistic regression model identified associated factors. Results A total of 397 patients were identified. The observed rates of transient, protracted, and definite PT-hypoPTH were 32.9%, 15.1%, and 5.2%, respectively. Rates of VDD were higher in the early-recovery PT-hypoPTH group (55.2% vs 31.5%; P = .01). Preoperative VDD was associated with faster PFR (19 vs 35 days; P = .03) and behaved as a protective factor for protracted PT-hypoPTH (odds ratio 0.47; 95% CI, 0.25-0.881; P = .016) in the multivariable analysis. Conclusion Preoperative VDD could act as a preconditioning factor of the parathyroid glands prior to the surgical aggression exerted against them during surgery aiding PFR. Basic research studies and prospective clinical trials are needed to explain the underlying physiological mechanisms and to provide further evidence to improve clinical management.