Immunotherapy, so promising in many neoplasms, still does not have a precise role in the treatment of neuroendocrine neoplasms (NENs). In this article, we provide an overview on the current knowledge about immunotherapy with immune checkpoint inhibitors (ICIs) applied to NENs, evaluating future perspectives in this setting of tumors.Evidence so far available for ICIs in gastroenteropancreatic (GEP)-NENs is definitively not as robust as for other tumors such as Small Cell Lung Cancer or Merkel Cell Carcinoma. In fact, with regard to the well-differentiated forms of NENs (NETs), the results obtained nowadays have been disappointing. However, the near future, might reserve interesting results for ICIs in GEP-NEN from a total of nine different ICI drugs, used throughout 19 randomised controlled trials. Such numbers highlight the growing attention gathering around NENs and ICIs, in response to the need of stronger evidences supporting such therapy.For the future, the most important aspect will be to study strategies that can make NETs more susceptible to response to ICI and, thus, enhance the effectiveness of these treatments. Therefore, the combination of conventional therapy, target therapy and immunotherapy deserve attention and warrant to be explored. A sequential chemotherapy, possibly inducing an increase in tumor mutational burden and tested before immunotherapy, could be a hypothesis deserving more consideration. A radiation treatment that increases tumor-infiltrating lymphocytes, could be another approach to explore before ICIs in NENs. Equally essential will be the identification of biomarkers useful for selecting patients potentially responsive to this type of treatment.

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology.

Background: Anti-Müllerian hormone (AMH) decreases acutely after post-surgical radioactive iodine (RAI) ablation in females with differentiated thyroid cancer (DTC). Aim: We performed a cross-sectional and prospective study on AMH levels in pre-menopausal females with a history of DTC. Methods: Fifty-nine females after surgery and RAI (group 1) and 30 females after surgery alone (group 2) were studied. The control group consisted of 141 healthy women (group 3). The prospective study was performed in 43 and 14 females from groups 1 and 2, respectively. Results: On first evaluation, AMH levels were similar in groups 1 and 2, but lower than in group 3. In all groups, AMH was negatively related with chronological age and FSH levels. When subjects were stratified according to age, AMH levels were not different between groups. When AMH was evaluated up to 2 years after the baseline evaluation, no changes emerged in either group of women with DTC. In the prospective study, the incidence of abnormal menstrual cycles and the onset of menopause were observed in similar percentages of women with a history of RAI-treated DTC and of those treated with surgery alone. Conclusions: AMH can be considered a reliable index of ovarian reserve in women with DTC. Chronological age is the main factor influencing AMH levels in both DTC patients and controls. After age-related stratification, AMH levels are similar in women with DTC treated with RAI and those treated with surgery alone.

Objective: To evaluate the left ventricular mass (LVM) reduction induced by dietary sodium restriction. Patients and Methods: A simple sodium-restricted diet was advised in 138 treated hypertensives. They had to avoid common salt loads, such as cheese and salt-preserved meat, and were switched from regular to salt-free bread. Blood pressure (BP), 24-h urinary sodium (UNaV) and LVM were recorded at baseline, after 2 months. and after 2years. Results: In 76 patients UNaV decreased in the recommended range after 2 months and remained low at 2 years. In 62 patients UNaV levels decreased after 2 months and then increased back to baseline at 2 years. Initially the two groups did not differ in terms of BP (134.3 ± 16.10/80.84 ± 12.23 vs. 134.2 ± 16.67/81.55 ± 11.18 mmHg, mean ± SD), body weight (72.64 ± 15.17 vs. 73.79 ± 12.69 kg), UNaV (161.0 ± 42.22 vs. 158.2 ± 48.66 mEq/24 h), and LVM index (LVMI; 97.09 ± 20.42 vs. 97.31 ± 18.91 g/m²). After 2years. they did not differ in terms of BP (125.3 ± 10.69/74.97 ± 7.67 vs. 124.5 ± 9.95/75.21 ± 7.64 mmHg) and body weight (71.14 ± 14.29 vs. 71.50 ± 11.87 kg). Significant differences were seen for UNaV (97.3 ± 23.01 vs. 152.6 ± 49.96 mEq/24 h) and LVMI (86.38 ± 18.17 vs. 103.1 ± 21.06 g/m²). Multiple regression analysis: UNaV directly and independently predicted LVMI variations, either as absolute values (R² = 0.369; β = 0.611; p < 0.001), or changes from baseline to +2years. (R² = 0.454; β = 0.677; p < 0.001). Systolic BP was a weaker predictor of LVMI (R² = 0.369; β = 0.168; p = 0.027; R² = 0.454; β = 0.012; p = 0.890), whereas diastolic BP was not correlated with LVMI. The prevalence of left ventricular hypertrophy decreased (29/76 to 15/76) in the first group while it increased in the less compliant patients (25/62 to 36/62; Chi²p = 0.002). Conclusion: LVM seems linked to sodium consumption in patients already under proper BP control by medications.