How much does obesity affect the male reproductive function?

Obesity is considered a worldwide epidemic disease. Many pathological conditions have been associated to obesity but the evidence relating to impaired fertility in males with obesity are contrasting. The aim of this review was to evaluate the interplay between obesity and male fertility, analyzing evidence from in vitro and in vivo studies to clinical trials. Obesity seems to be responsible of secondary hypogonadism. Here, we propose a new classification including central, peripheral and testicular factors that may affect the hypothalamic-pituitary-gonadal axis. Moreover, some studies demonstrated a direct action of obesity on sperm count and sperm characteristics, mediated by impaired Sertoli cells function, increased scrotal temperature, oxidative stress and accumulation of toxic substances and liposoluble endocrine disruptors in fat tissue. Recent studies have explored obesity-related epigenetic effects in sperm cells which may cause diseases in offspring. Moreover, not only in females but also males, obesity has been linked to reduced outcomes of in vitro fertilization, with a reduction of pregnancy rate and an increase of pregnancy loss. Finally, we reviewed the effects of weight modifications through diet or bariatric surgery on obesity-related reproductive dysfunction. In this regard, several studies have demonstrated that weight loss has been associated with a restoration of gonadal hormones levels

Role of FGF System in Neuroendocrine Neoplasms. Potential Therapeutic Applications

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors originating from neuroendocrine cells dispersed in different organs. Receptor tyrosine kinases are a subclass of tyrosine kinases with a relevant role in several cellular processes including proliferation, differentiation, motility and metabolism. Dysregulation of these receptors is involved in neoplastic development and progression for several tumors, including NENs. In this review, we provide an overview concerning the role of the fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) system in the development and progression of NENs, the occurrence of fibrotic complications and the onset of drug-resistance. Although no specific FGFR kinase inhibitors have been evaluated in NENs, several clinical trials on multitarget tyrosine kinase inhibitors, acting also on FGF system, showed promising anti-tumor activity with an acceptable and manageable safety profile in patients with advanced NENs. Future studies will need to confirm these issues, particularly with the development of new tyrosine kinase inhibitors highly selective for FGFR

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

Ruolo diagnostico, prognostico e predittivo di risposta del NETest nelle neoplasie neuroendocrine

Il NETest è una metodica di biologia molecolare e, in particolare, di biopsia liquida, applicata alle neoplasie neuroendocrine (NEN), che si propone come nuovo biomarcatore altamente sensibile e specifico. Il NETest consente una sorta di gene signature del tumore, definendone il profilo trascrizionale mRNA, estratto dal sangue periferico. L’applicazione pratica è nella diagnosi, dove il NETest sembra identificare anche piccoli tumori localizzati, nella definizione prognostica, con l’identificazione dei tumori con maggiore tendenza alla progressione e alla recidiva post-chirurgica, nella riposta ai trattamenti, con l’identificazione precoce di progressione nel corso di terapie anti-tumorali. A fronte di risultati iniziali estremamente promettenti, il NETest necessita di una conferma su larga scala, in ampie casistiche multicentriche

Pituitary adenoma consistency affects postoperative hormone function: a retrospective study

Background: Tumor consistency recently emerged as a key factor in surgical planning for pituitary adenomas, but its impact on postoperative endocrine function is still unclear. Our study aimed to evaluate the impact of tumor consistency on the development of postoperative pituitary deficiencies. Methods: Single-center, retrospective analysis of consecutive pituitary surgeries performed between January 2017 and January 2021 at Policlinico Umberto I in Rome. All patients underwent radiological and biochemical evaluations at baseline, and hormone assessments 3 and 6 months after pituitary surgery. Postoperative MRI studies were used to determine resection rates following surgery. Data on tumor consistency, macroscopic appearance, neurosurgical approach, and intraoperative complications were collected. Results: Fifty patients [24 women, mean age 57 ± 13 years, median tumor volume 4800 mm3 [95% CI 620-8828], were included. Greater tumor volume (χ2 = 14.621, p = 0.006) and male sex (χ2 = 12.178, p < 0.001) were associated with worse preoperative endocrine function. All patients underwent transsphenoidal adenomectomy. Fibrous consistency was observed in 10% of patients and was associated with a Ki-67 greater than 3% (χ2 = 8.154, p = 0.04), greater risk of developing postoperative hormone deficiencies (χ2 = 4.485, p = 0.05, OR = 8.571; 95% CI: 0.876-83.908), and lower resection rates (χ2 = 8.148, p = 0.004; OR 1.385, 95% CI; 1.040-1.844). Similarly, worse resection rates were observed in tumors with suprasellar extension (χ2 = 5.048, p = 0.02; OR = 6.000, 95% CI; 1.129-31.880) and CSI (χ2 = 4.000, p = 0.04; OR = 3.857, 95% CI; 0.997-14.916). Conclusions: Tumor consistency might provide useful information about postoperative pituitary function, likely due to its impact on surgical procedures. Further prospective studies with larger cohorts are needed to confirm our preliminary findings

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)

Rediscovering biomarkers in for the diagnosis and early treatment response in NEN. Reborn Study

Introduction: Neuroendocrine neoplasms (NENs) are heterogeneous in terms of primary site, behavior, and response to treatment. The possibility to rely on diagnostic and prognostic circulating biomarkers is an unmet need in NENs. Despite promising, the clinical role of circulating angiogenic markers remains unclear. In addition, liquid biopsy is currently receiving growing attention in oncology, but data in NENs are available only for circulating nucleic acids and tumor cells while the potential role of circRNA sequencing from tumor educated platelets (TEPs) has never been explored. The aim of this study was to evaluate the role of angiogenic markers and circRNA sequencing from TEPs in NENs diagnosis and prognosis. Materials and Methods: We performed a prospective observational study including 46 consecutive patients with proven NENs of pulmonary and gastro-entero-pancreatic (GEP) origin and 29 controls. Circulating pro-angiogenic factors were measured by ELISA assay, and ANG2 tissue expression was evaluated by immunohistochemistry. A limited subgroup of patients, affected by well-differentiated GEP NET, grade G1 or G2, naïve to any medical treatment, was also included in a proof-of-concept pilot study, for analyzing the expression profile of circRNA derived from TEPs, both at baseline and early follow-up (after 3 months of treatment). Results: The study demonstrated a significantly higher level of ANG2, ANG1, sTIE2, and PROK2 in patients affected by NENs compared to controls. In the subgroup of patients with NENs, ANG2 levels were higher in poorly differentiated NENs (4.9, 2.8–7.4) than in well-differentiated (3.2, 1.7–6.4) ng/ml, p = 0.046 and in tumor stage 3–4 compared to stage 1–2: 4.2 (2.7–8.7) vs 2.7 (1.5–5.7), p = 0.044. ANG2 and PROK2 were significantly higher in patents with progressive disease compared to stable disease at the moment of sampling: ANG2 = 6.3 (4.0–11.0) vs 2.7 (1.7–4.7) pg/ml, p = 0.001; PROK2 = 29.2 (28.4–32.3) vs 28.4 (28.1–28.9) pg/ml, p = 0.035. ANG2 was also higher in patients who developed progression (or died) during the follow-up (one year after the enrollment) than in patients with stable disease (2.3 (1.5-3.8) ng/ml vs 6.3 (4.2-10.1) ng/ml, p<0.001). Immunohistochemistry confirmed ANG2 and PROK2 expression in tumor specimens. We identified a large number of circRNA in this study (98,735), of which 63,562 were not previously annotated and 35,173 annotated. To investigate the potential role of circRNAs expression profile from TEPs as diagnostic and prognostic biomarkers, a bioinformatic analysis is ongoing to evaluate differently expressed circRNA from TEPs between patients and controls and in the same patients before and after treatment. Conclusions: We demonstrated higher levels of angiogenic markers in NENs, with a correlation between ANG2 serum levels and NENs morphology and staging. In both GEP and lung NENs, ANG2 and PROK2 are higher in case of tumor progression, suggesting a potential role as prognostic markers in NENs patients. The study also demonstrated that TEPs are a good source of circRNA in patients affected by NENs. The bioinformatics analyses are currently ongoing and could be the base for the development of novel markers for the diagnosis and follow-up of patients affected by NENs

Manuale di Medicina e Chirurgia - Tomo 9 Malattie dell'apparato locomotore

Il Tomo 9 del Manuale di Medicina e Chirurgia si rivolge ai medici che vogliono prepararsi per le selezioni del Concorso nazionale per le Scuole di specializzazione o del Corso di formazione specifica in Medicina generale. Il volume, interamente a colori e ricco di illustrazioni, secondo quanto previsto dalle nuove metodologie didattiche, contiene anche mappe concettuali sulle patologie oggetto di studio. Gli ambiti esaminati sono Ortopedia, Traumatologia e Medicina dello sport. Il testo, dopo una panoramica su embriologia, organogenesi e istologia dell’apparato locomotore, analizza le infezioni osteo-articolari, le malattie degenerative e metaboliche, le lesioni traumatiche, i tumori e le patologie pseudo-tumorali, le malattie ortopediche pediatriche, le patologie della spalla e del braccio, del polso e della mano, del collo e del rachide, del cingolo pelvico, del ginocchio e della gamba, della caviglia e del piede. Per ciascuna patologia si delineano il quadro clinico, la sintomatologia, gli esami strumentali, il trattamento, conservativo o chirurgico, e le eventuali complicanze. Il volume è completata da quiz a risposta multipla per la verifica delle conoscenze acquisit