Impact of long-acting octreotide in patients with early-stage MEN1-related duodeno-pancreatic neuroendocrine tumours.

BACKGROUND: Somatostatin analogues (SSA) represent one of the main therapeutic option in patients affected with functioning well-differentiated neuroendocrine tumours (NETs). There are no studies specifically focusing on NETs associated with Multiple Endocrine Neoplasia type 1 (MEN1). AIM: To evaluate the efficacy of the long-acting SSA octreotide in MEN1 patients with early-stage duodeno-pancreatic NETs. PATIENTS AND METHODS: Forty patients with MEN1 were retrospectively evaluated. Twenty patients with evidence of one or more MEN1-related duodeno-pancreatic NETs < 20 mm in size (age range 26-61 years) were treated with octreotide long-acting octreotide (LAR) as first-line therapy. Treatment duration ranged 12-75 months. At the baseline radiological evaluation, multiple duodeno-pancreatic NETs (range 1-8, size 3-18 mm) were detected. RESULTS: An objective tumour response was observed in 10%, stable disease in 80% and progression of disease in 10% of cases. In six patients with abnormally increased CgA, gastrin and/or insulin serum concentrations, a significant clinical and hormonal response occurred in 100% of cases and was stable along the time. CONCLUSIONS: Therapy with SSA is highly safe and effective in patients with early-stage MEN1 duodeno-pancreatic NETs, resulting in long-time suppression of tumour and hormonal activity and 10% objective response. This suggests to early start therapy with SSA in patients with MEN1-related NETs.

Impact of cinacalcet hydrochloride in clinical management of primary hyperparathyroidism in multiple endocrine neoplasia type 1.

AIM: Primary hyperparathyroidism (PHPT) is one of main cause of morbidity in patients with multiple endocrine neoplasia type 1 (MEN1). Medical therapy with cinacalcet-hydrochloride may modify the therapeutic strategy of MEN1 related PHPT. We present an experience with cinacalcet-hydrochloride in two patients with MEN1 PHPT. METHODS: The study included two MEN1 patients belonging to the same family (a 50-year-old woman and her daughter aged 20 years) with PHPT secondary to multiple involvement of parathyroid glands and other MEN1 related tumors. As both patients refused to undergo parathyroid surgery, we decided to start medical treatment with cinacalcet at the dose of 30 mg/day, which was the first treatment for the youngest patient, while the oldest had already been treated with partial parathyroidectomy. Serum concentrations of PTH, calcium and phosphorus, 24-h urine calcium-to-creatinine ratio and renal-threshold-phosphate concentration were evaluated before and after therapy. RESULTS: Serum calcium and PTH levels were normalized after 1 and 6 months of therapy, respectively, and 60 and 54 months after the beginning of cinacalcet remained normal. Hypercalciuria, hypophosphoremia and renal-threshold-phosphate normalized during therapy with cinacalcet. At ultrasonography, parathyroid nodular lesion remained unchanged. Cinacalcet was well tolerated without occurrence of side effects. CONCLUSION: Cinacalcet seems to be highly effective in controlling PHPT in patients with MEN1 either in naïve patients or in those with postsurgical recurrence. If cinacalcet will be confirmed to ensure a long-time control of PHPT or even to prevent the development and progression of PHPT, this may led to modify the therapeutic strategy of MEN1 PHPT.

Histone deacetylase inhibitors in the treatment of hematological malignancies.

Histone deacetylases (HDACs) play a central role in the epigenetic regulation of gene expression. Aberrant activity of HDACs has been found in several human cancers leading to the development of HDAC inhibitors (HDACi) as anti-tumors drugs. In fact, over the last years, a number of HDACi have been evaluated in clinical trials; these drugs have the common ability to hyperacetylate both histone and non-histone targets, resulting in a variety of effects on both cancer cells and immune responses. Clinical trials of HDACi conducted in solid tumors and hematological malignancies have shown a better clinical efficacy of these drugs in hematological malignancies. In this review, will be highlighted the mechanisms of action underlying the clinical responses obtained with these drugs and the doubts regarding the use of HDACi in cancer therapy.

[Long-term treatment with medroxyprogesterone in 4 children with true precocious puberty]. / Trattamento a lungo termine con medrossiprogesterone acetato in quattro bambine affette da pubertà precoce vera

PIP: The article presents the case of 4 little girls, aged 7-9, affected by true pubertas praecox, with secondary sex characteristics, menstruation, and precocious skeletal growth. One of the girls was also affected by epilepsy, and one by McCune-Albright syndrome. All girls were treated, over a period of 2-5 years, with injections of medroxyprogesterone acetate. Such treatment caused, in all patients, regression of mammary hypertrophy, reduction of plasma gonadotropins, and disappearance of menstruation. Skeletal growth was slowed down, thus improving prognosis for final stature. Such results coincide with others published in the literature on the subject.^ieng