Cardio-Metabolic Indices and Metabolic Syndrome as Predictors of Clinical Severity of Gastroenteropancreatic Neuroendocrine Tumors

Background: Obesity, mainly visceral obesity, and metabolic syndrome (MetS) are major risk factors for the development of type 2 diabetes, cardiovascular diseases, and cancer. Data analyzing the association of obesity and MetS with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are lacking. Fatty liver index (FLI) is a non-invasive tool for identifying individuals with non-alcoholic fatty liver disease (NAFLD). Visceral adiposity index (VAI) has been suggested as a gender-specific indicator of adipose dysfunction. Both indexes have been proposed as early predictors of MetS. This study aimed to investigate the association of FLI VAI as early predictors of MetS with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: A cross-sectional, case–control, observational study was carried out at the ENETS Centers of Excellence Multidisciplinary Group for Neuroendocrine Tumors, University “Federico II”. VAI and FLI were calculated. Results: We enrolled 109 patients with histologically confirmed G1/G2 GEP-NET (53 M; 57.06 ± 15.96 years), as well as 109 healthy subjects, age, sex- and body mass index-matched. Forty-four GEP-NET patients were G2, of which 21 were with progressive disease, and 27 patients had metastases. GEP-NET patients had a higher value of VAI (p < 0.001) and FLI (p = 0.049) and higher MetS presence (p < 0.001) compared with controls. VAI and FLI values and MetS presence were higher in G2 than in G1 patients (p < 0.001), in patients with progressive disease, and in metastatic vs non-metastatic patients (p < 0.001). In addition, higher values of VAI and FLI and higher MetS presence were significantly correlated with the worst clinical severity of NENs. The cut-off values for the FLI and MetS to predict high grading of GEP-NETs and the presence of metastasis were also provided. Conclusions: This is the first study investigating an association between VAI and FLI as early predictors of MetS and GEP-NET. Our findings report that the worsening of clinicopathological characteristics in GEP-NET is associated with higher presence of MetS, NAFLD, evaluated by FLI, and visceral adiposity dysfunction, evaluated by VAI. Addressing the clinical evaluation of MetS presence, NAFLD, and visceral adiposity dysfunction might be of crucial relevance to establish targeted preventive and treatment interventions of NEN-related metabolic comorbidities

Acclimation to changing light conditions of long-term shade-grown beech (Fagus sylvatica L.) seedlings of different geographic origins

Effects of changing light conditions on the ecophysiological condition behind survival were examined on beech from two different populations. Plants were grown in a greenhouse under simulated understorey and canopy gap light conditions. Upon exposure to high light maximum photosynthesis of shade-acclimated leaves increased followed by a reduction over several days to between high- and low-light control rates. In the reciprocal transfer, the decrease in maximum photosynthesis was rapid during the first 2–3 days and then levelled off to values comparable to low-light controls. Seedlings from Sicily (Madonie) showed generally higher maximum photosynthetic rates than those from Abetone. Leaf conductance varied in the same direction as photosynthesis in high- to low-light seedlings but to a lesser degree. Leaves grown under low light and exposed to high light experienced photoinhibition. The Abetone population was more susceptible to photoinhibitory damage than the seedlings from Sicily. Exposure to high light of shade-acclimated seedlings resulted in intermediate chlorophyll concentrations between levels of the high-light and low-light seedlings. Carotenoid concentration was unaffected by treatments. Seedlings grew more in high light, but had a lower leaf area ratio. Light-limited seedlings showed a shift in carbon allocation to foliage. Leaves formed in the new light regime maintained the same anatomy that had been developed before transfer. Seedlings from Sicily had thicker leaves than those of seedlings from Abetone. Seedlings from Abetone were found to be more susceptible to changing light conditions than seedlings from Sicily. We conclude that small forest gaps may represent a favorable environment for photosynthesis and growth of beech regeneration as a result of the limited ability of seedlings to acclimate to sudden increases in high irradiance and because of the moderate levels of light stress in small gaps

Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case–control study

Purpose: Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for NENs. Methods: We performed a retrospective case–control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors. Results: Mean age was 58.3 ± 15.8&nbsp;years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31–3.55, p = 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39–4.51, p = 0.002) and obesity (OR 1.88, 95% CI 1.18–2.99, p = 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08–0.93, p = 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05–5.46, p = 0.035) and progressive disease (OR 2.47, 95% CI 1.08–5.34, p = 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28–5.15, p = 0.008) and obesity (OR 1.98, 95% CI 1.11–3.52, p = 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38–4.38, p = 0.003) and obesity (OR 1.90, 95% CI 1.08–3.33, p = 0.026). Conclusion: This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs