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La sindrome da carcinoide, la cui incidenza e in aumento, rappresenta e la piu frequente sindrome correlata ai tumori neuroendocrini (NET). L’eziopatogenesi non e ancora chiaramente definita, anche se e ormai chiaro assodato il ruolo patogenetico della serotonina. Il quadro clinico e dominato da diarrea e flushing, che possono assumere diverse caratteristiche a seconda della sede del tumore (midgut o foregut). La piu grave associazione e la cardiopatia da carcinoide, spesso asintomatica ma che necessita di screening e follow-up per prevenirne le gravi conseguenze. La diagnosi biochimica si basa sulla misura dell’acido 5-idrossi-indolacetico (5-HIAA) nelle urine delle 24 ore e, quando e dove disponibile, anche sulla sua concentrazione ematica. La terapia medica classica si basa sugli analoghi della somatostatina, ma stanno tuttavia emergendo nuove possibilita di trattamento (inibitori della sintesi della serotonina e terapia radiorecettoriale). Necessaria un’adeguata prevenzione delle crisi da carcinoide che possono essere associate a interventi chirurgici e anestesia. Diagnosi tempestiva e appropriata e follow-up integrato sono garanzie per una gestione ottimale della condizione morbosa.

Hypothyroidism is a common side effect of Sunitinib (SUN) treatment in metastatic renal cell carcinoma (mRCC) patients. We aimed to evaluate thyroid profile during the alternative 2/1 SUN treatment schedule and to assess the predictive value of hypothyroidism in terms of survival. We performed a prospective observational study enrolling 42 consecutive mRCC patients starting first-line alternative SUN dosing 2/1 schedule. Thyroid function was assessed at baseline and during the first three SUN cycles (1 cycle = 6 weeks = 2 ON/1 OFF + 2 ON/1 OFF), and then after 6 and 12 months. Thyroid ultrasound was performed at baseline and after 3, 6, and 12 months. Subclinical hypothyroidism developed in 24% of patients during the first cycle; in other 24% in the second cycle and in 14% in the third cycle. The highest TSH values were reached during the second cycle, ON phase (6.58 ± 5.74 μI U/l). We observed a reduction in thyroid size, in echogenicity and in parenchymal perfusion in all patients. Progression-free survival (PFS) tended to be longer in patients with TSH ≥ 5 μI U/ml during the second cycle (p = 0.069). TSH level was an independent risk factor for PFS in men (p = 0.009) but not in women (p = 0.285). This is the first study investigating functional and morphological effects on thyroid during the alternative 2/1 SUN schedule in mRCC patients. We detected an early onset of subclinical hypothyroidism, observing the association between TSH ≥ 5 μI U/ml and: (i) longer PFS in men; (ii) progressive decrease of thyroid size in absence of significant changes in autoimmune thyroid profile.

Given the increasing incidence of neuroendocrine neoplasms (NENs) over the past few decades, a more comprehensive knowledge of their pathophysiological bases and the identification of innovative NEN biomarkers represents an urgent unmet need. There is still little advance in the early diagnosis and management of these tumors, due to the lack of sensible and specific markers with prognostic value and ability to early detect the response to treatment. Chronic systemic inflammation is a predisposing factor for multiple cancer hallmarks, as cancer proliferation, progression and immune-evading. Therefore, the relevance of inflammatory biomarkers has been identified as critical in several types of tumours, including NENs. A bidirectional relationship between chronic inflammation and development of NENs has been reported. Neuroendocrine cells can be over-stimulated by chronic inflammation, leading to hyperplasia and neoplastic transformation. As the modulation of inflammatory response represents a therapeutic target, inflammatory markers could represent a promising new key tool to be applied in the diagnosis, the prediction of response to treatment and also as prognostic biomarkers in NENs field. The present review provides an overview of the pre-clinical and clinical data relating the potentially usefulness of circulating inflammatory markers: neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), cytokines and tissue inflammatory markers (PD-1/PD-L1), in the management of NENs. (1) NLR and PLR have both demonstrated to be promising and simple to acquire biomarkers in patients with advanced cancer, including NEN. To date, in the context of NENs, the prognostic role of NLR and PLR has been confirmed in 15 and 4 studies, respectively. However, the threshold value, both for NLR and PLR, still remains not defined. (2) Cytokines seem to play a central role in NENs tumorigenesis. In particular, IL-8 levels seems to be a good predictive marker of response to anti-angiogenic treatments. (3) PD-1 and PD-L1 expression on tumour cells and on TILs, have demonstrated to be promising predictive and prognostic biomarkers in NENs. Unfortunately, these two markers have not been validated so far and further studies are needed to establish their indications and utility.

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

La versione originale di questo articolo purtroppo conteneva un errore. I nomi di due farmaci sono stati erroneamente inseriti nella tabella al momento della pubblicazione iniziale. La tabella corretta e riportata di seguito e la tabella dell’articolo originale e stata aggiornata. L’editore desidera scusarsi per questo errore. QUADRO SINOTTICO DEI FARMACI CITATI Principio attivo Nomi commerciali Dosaggi Octreotide Sandostatina fl 50 mcg/ml, 100 mcg/ml, 500 mcg/ml; sc, ev Octreotide LAR Sandostatina LAR 1 fl 10 mg, 20 mg, 30 mg; im (ogni 28 giorni) Lanreotide Ipstyl 1 fl 60 mg, 90 mg, 120 mg; im (ogni 14, 21, 28 giorni) Telotristat Xermelo cp 250 mg; os Pasireotide Signifor fl 0,3 mg, 0,6 mg, 0,9 mg; sc Everolimus Afinitor cp 2,5 mg, 5 mg, 10 mg: os 177Lu-DOTATATE Lutathera fl 370 MBq/mL; ev 131I-MIBG Iobenguano 131 I fl 185 MBq/ml, 246,7 MBq/ml, 493,3 MBq/ml; ev

Acromegaly is a chronic debilitating disorder resulting from excessive secretion of growth hormone (GH) and consequent increase in insulin-like growth factor I (IGF-I), usually caused by a pituitary somatotroph adenoma. Effective treatment aims to ameliorate symptoms and signs of the disease and to lower mortality rate. In particular, high morbidity and mortality are partly related to the presence of insulin resistance due to the action of GH on liver, muscle and adipose tissue. Insulin resistance and/or reduced insulin sensitivity physiologically result in hypersecretion of insulin from the pancreas. This compensatory state of hyperinsulinemia is felt to be a first and more important marker for this condition. Adequate control of GH excess by surgery or pharmacotherapy is associated with decreased insulin resistance, resulting in reduced plasma insulin and glucose levels or improved glucose tolerance. Despite divergent effects of both somatostatin and somatostatin analogs on GH, insulin and glucagon secretion, and glucose absorption, treatment with the somatostatin analogs octreotide and lanreotide has only limited effects on glucose metabolism. However, glucose sensitivity has been formally examined using a hyperinsulinemic euglycemic clamp only in a minority of studies. Treatment with the GH-receptor antagonist pegvisomant improves insulin sensitivity, thus decreasing circulating fasting insulin and glucose levels. Assessment of insulin secretion and glucose levels in acromegalic patients during administration of the above compounds is thus mandatory.