The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs (n = 96) were cross-matched for age, gender, and district of residence with a control group (n = 96) derived from the general population in a case-control study. Patients presented gastro-intestinal (75.0%) or pancreatic (22.9%) tumors, grade G1 (66.7%) or G2 (27.1%) with localized disease (31.3%), regional metastasis (16.7%) or distant metastasis (43.8%) at diagnosis, and 45.8% had clinical hormonal syndromes. MetS was defined according to Joint Interim Statement (JIS) criteria. Well-differentiated GEP-NETs were associated with MetS criteria as well as the individual components’ waist circumference, fasting triglycerides, and fasting plasma glucose (p = 0.003, p = 0.002, p = 0.011 and p < 0.001, respectively). The likelihood of the association was higher when the number of individual MetS components was greater than four. MetS and some individual MetS components including visceral obesity, dyslipidemia, and increased fasting glucose are associated with well-differentiated GEP-NET. This data provides a novel insight in unraveling the mechanisms leading to GEP-NET disease.

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30–14.53) and disseminated disease (OR 4.52 95%CI 1.44–14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.

COVID-19 is an intriguing infectious condition with multisystemic manifestations and variable outcomes that are influenced by the concomitant presence of non-communicable diseases, such as obesity, diabetes, and cardiovascular disease, which were previously well established epidemics and therefore are considered global syndemics. Although an enormous progress towards understanding mechanisms of SARS-CoV-2 infection leading to COVID-19 has been made, there are still many areas of uncertainty to clarify. Systemic diseases are characterized by common links that allow integrating apparently unrelated disease manifestations. The authors launch the provocative hypothesis that serotonin is the putative mediator linking the lung, gut, cardiac, neurological, and other systemic manifestations that characterize severe COVID-19 in individuals with diabetes and obesity. In support of a role for serotonin in the mechanisms leading to disease severity are the similarities between acute and post-acute COVID-19 manifestations and neuroendocrine tumors presenting with carcinoid syndrome. Scientific discussion is set by highlighting the available clues that support this working hypothesis to trigger future research aimed at unravelling the molecular pathways underlying SARS-CoV-2 infection that are still far from being fully disclosed.

The association of well-differentiated gastro-entero-pancreatic neuroendocrine neoplasia (WD GEP-NEN) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. However, whether obesity and metabolic syndrome risk factors are associated with GEP-NEN adverse outcomes and the poorer prognosis was unknown. The present study aimed to evaluate whether the presence of MetS or any of its individual components at WD GEP-NEN diagnosis influenced disease outcomes. A cohort of patients with non-localized WD GEP-NETs (n = 81), was classified according to the primary tumor site (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (3% ≤ Ki67 ≤ 20%) (WHO 2010)), disease extension (loco-regional or metastatic disease), presence of hormonal secretion syndrome (functioning or non-functioning), and evaluated for the presence of MetS criteria at diagnosis. MetS was present in 48 (59.3%) patients. During a median follow-up of 95.0 months (16.8–262.5), 18 patients died of the disease (10 with MetS vs. 8 without MetS). Overall survival (OS) at 5 years was 87.1% (95% CI: 73.6–94.0) for MetS and 90.9% (95% CI: 74.4–97.0) for non-Mets group, while OS at 10 years was 72.5% (95% CI: 55.3–84.0) for MetS, and 76.4% (95% CI: 53.6–89.0) for non-MetS group. Progression-Free Survival (PFS) at 5 years was 45.9% (95% CI: 30.8–59.8) for MetS and 40.0% (95% CI: 21.3–58.1) for non-MetS group, and PFS at 10 years was 18.1% (95% CI: 7.0–33.5) for MetS and 24.4% (95% CI: 9.0–43.7) for non-MetS group. Waist circumference (WC), a surrogate measure for visceral obesity, was associated with significantly shorter PFS (HR = 1.03; 95% CI: 1.01–1.06), although did not influence OS (HR = 1.01; 95% CI: 0.97–1.06). The findings of this study reinforce a potential link between visceral obesity and GEP-NEN and further suggest that obesity could influence disease prognosis.