R Severino

University of Naples Federico II, Napoli, Campania, Italy

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Publications (8)23.18 Total impact

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    ABSTRACT: Pancreatic vipoma is an extremely rare tumor accounting for less than 2% of endocrine pancreatic neoplasms with a reported incidence of 0.1-0.6 per million. While cross-sectional imaging findings are usually not specific, exact localization of the tumor by means of either computed tomography (CT) or magnetic resonance (MR) is pivotal for surgical planning. However, cross-sectional imaging findings are usually not specific and further characterization of the tumor may only be achieved by somatostatin-receptor scintigraphy (SRS). We report the case of a 70 years old female with a two years history of watery diarrhoea who was found to have a solid, inhomogeneously enhancing lesion at the level of the pancreatic tail at Gadolinium-enhanced MR (Somatom Trio 3T, Siemens, Germany). The tumor had been prospectively overlooked at a contrast-enhanced multi-detector CT (Aquilion 64, Toshiba, Japan) performed after i.v. bolus injection of only 100 cc of iodinated non ionic contrast media because of a chronic renal failure (3.4 mg/mL) but it was subsequently confirmed by SRS. The patient first underwent a successful symptomatic treatment with somatostatin analogues and was then submitted to a distal pancreasectomy with splenectomy to remove a capsulated whitish tumor which turned out to be a well-differentiated vipoma at histological and immuno-histochemical analysis.
    World Journal of Radiology. 10/2014; 6(10):840-845.
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    ABSTRACT: Neuroendocrine tumors (NETs) can be sporadic or they can arise in complex hereditary syndromes. Patients with hereditary NETs can be identified before the development of tumors by performing genetic screenings. The aim of the study was to evaluate the clinical and prognostic impact of a preclinical genetic screening in subjects with hereditary NET syndromes. 46 subjects referred for hereditary NET syndrome [22 MEN1, 12 MEN2, 12 Familial Paragangliomatosis (FPGL)] were enrolled and divided in 2 groups (group A, 20 subjects with clinical appearance of NET before the genetic diagnosis; group B, 26 subjects with genetic diagnosis of hereditary NET syndromes before the clinical appearance of NETs). The main outcome measures were severity of disease, prognosis, and survival. The rate of surgery for MEN1-, MEN2-, FPGL4-related tumors was 90% in group A and 35% in group B (p<0.01). Both symptoms related to tumors and symptoms related to therapies were significantly less frequent in group B than in group A (p<0.05). Tumor stage was locally advanced or metastatic in 50% of group A and in no one of group B (p<0.01). The mortality rate was 25% in group A and 0% in group B (p<0.05). An early genetic screening for hereditary NET syndromes results in an improvement in clinical presentation and morbidity. A potential impact of the genetic screening on the mortality rate of these subjects is suggested and needs to be investigated in further and more appropriate studies.
    Hormone and Metabolic Research 10/2011; 43(11):794-800. · 2.15 Impact Factor
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    ABSTRACT: Everolimus, an mTOR inhibitor, which has been demonstrated to induce anti-tumour effects in different types of neuroendocrine tumours, has never been evaluated in patients with medullary thyroid cancer (MTC). The aim of this study was to evaluate the in vitro and in vivo effects of everolimus in combination with octreotide in MTC. Two patients with progressive metastatic MTC and high calcitonin levels were treated with everolimus 5-10 mg/day. Both patients were under treatment with octreotide LAR at the study entry. An in vitro study was also performed to assess everolimus effects on MTC cell lines (TT and MZ-CRC-1 cells). A tumour response was observed in both patients. Serum calcitonin decreased by 86% in patient 1 and by 42% in patient 2. In TT and MZ-CRC-1 cells, everolimus induced a significant dose-dependent inhibition in cell proliferation. This effect seems to be related to a cell cycle arrest in G(0) /G(1) phase in both cell lines and to the induction of cellular senescence in TT cells. Everolimus in combination with octreotide may be active as anti-tumour therapy in patients with progressive metastatic MTC, suggesting to further evaluate this agent in MTC patients in a large prospective study.
    Journal of Cellular and Molecular Medicine 08/2011; 16(7):1563-72. · 4.75 Impact Factor
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    ABSTRACT: In patients with well-differentiated (WD) neuroendocrine tumors (NET), long-acting octreotide (LAR), conventionally administered at a dose of 30 mg every 28 days, has well-documented anti-secretive but limited antiproliferative effects. The objective of this study was to evaluate a different schedule of LAR treatment consistent with a shorter interval between administrations (21 days) in WDNET patients with progressive disease at standard-dose interval. Twenty-eight patients followed for diagnosis and therapy of WDNET who had tumor progression during therapy with LAR 30 mg every 28 days were enrolled. Clinical, biological, and objective tumor response was evaluated after LAR 30 mg every 21 days. Time to progression was also evaluated after LAR 30 mg every 21 days and compared to LAR 30 mg every 28 days. The treatment with LAR 30 mg every 21 days resulted in complete and partial control of clinical symptoms in 40% and 60% of cases, respectively. Circulating neuroendocrine markers were significantly decreased in 30% of cases. A stabilization of disease was obtained in 93% and objective response in 7%. The median time to progression was significantly longer by using the shortened interval of LAR administration as compared to the standard one (30 vs 9 months, p<0.0001). The treatment was safe and well tolerated. The shortened schedule of LAR administration was able to re-institute control of clinical symptoms, to decrease level of circulating neuroendocrine markers and to increase time to progression in patients previously escaping from a standard schedule treatment.
    Journal of endocrinological investigation 07/2011; 35(3):326-31. · 1.65 Impact Factor
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    ABSTRACT: Cinacalcet is effective in controlling the biochemical abnormalities in patients with primary hyperparathyroidism (PHPT) but it seems to be less effective on bone mineral density (BMD). In the same patients, bisphosphonates are reported to be effective on bone resorption but less effective on calcium and PTH excess. In this study, the efficacy of cinacalcet in combination with alendronate has been retrospectively evaluated in patients with PHPT. Twenty-three patients with PHPT who had not been operated were retrospectively investigated. Cinacalcet was evaluated in combination with alendronate in 10 of the 23 patients, and in monotherapy in 13 other patients. Serum calcium, phosphorus and PTH, 24 h urine calcium and phosphorus as well as BMD, evaluated by DXA and expressed as T-score, were measured before and after treatment. In all patients serum calcium and phosphorus and urinary calcium excretion were effectively and stably controlled and PTH was significantly decreased after treatment. There was no difference in the rate of serum calcium and PTH decrease between subjects treated with cinacalcet plus alendronate and those treated with cinacalcet alone. T-score increased by 9.6% at lumbar spine and 3.9% at femur level in the cinacalcet plus alendronate subgroup and was unchanged in the cinacalcet subgroup (P < 0.01). In patients with PHPT, the biochemical abnormalities are rapidly improved by cinacalcet regardless from the administration in monotherapy or in combination with alendronate. BMD is significantly improved in patients receiving cinacalcet plus alendronate and stable in those receiving cinacalcet in monotherapy.
    Endocrine 03/2011; 39(3):283-7. · 3.53 Impact Factor
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    ABSTRACT: AM: Patients with Fabry disease (FD), a genetic disorder caused by lysosomal a-galactosidase-A enzyme deficiency and characterized by a systemic accumulation of globotriaosylceramides, present high prevalence of subclinical hypothyroidism. The pathogenic mechanism is thought not to be related to anti-thyroid autoimmunity and may be dependent by intra-thyroid lipid accumulation. In this study, it was investigated whether thyroid function recovers in FD after long-term enzyme replacement therapy (ERT). Study population included 14 FD patients (7 females, 7 males, aged 21-62 years) and 14 sex- and age-matched normal subjects. Thyroid function was evaluated in each patient at baseline and after the beginning of ERT with rh-a-galactosidase-A (1 mg/kg/BW every 2 weeks) for three years. TSH levels were higher in FD patients than in controls (P<0.05). In FD patients, TSH levels were higher before than after ERT (1.9±0.2 vs 1.2±0.2 mU/L, P<0.01) while fT3 and fT4 levels were normal at baseline and unchanged after ERT. At baseline, TSH levels were >3 mU/L in three patients and normalize after ERT. Anti-Tg and/or anti-TPO titres were positive in 14% of patients and 21% of controls. After ERT, the rate of autoimmunity was unchanged. At the thyroid ultrasonography, a slight hypoechoic pattern was found in 71% of patients at baseline and decreased to 43% after ERT. Primary hypothyroidism in FD patients is reverted after long-term ERT. A screening of thyroid function and periodical re-evaluation during ERT is mandatory in all FD patients.
    Minerva endocrinologica 03/2011; 36(1):1-5. · 1.40 Impact Factor
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    ABSTRACT: The prognosis of medullary thyroid carcinoma (MTC) depends on the completeness of the first surgical treatment. To date, it is not possible to predict whether the tumor has been completely removed after surgery. The aim of this study was to evaluate the reliability of an intraoperative calcitonin monitoring as a predictor of the final outcome after surgery in patients with MTC. Twenty patients underwent total thyroidectomy and central lymph node dissection on the basis of a positive pentagastrin test. In six cases a preoperative diagnosis of MTC was achieved at the cytological examination. During the surgical intervention, calcitonin was measured at the time of anesthesia, at the time of manipulation, and 10 and 30 min after surgical excision. At the histological examination, 10 patients had MTC and 10 had C cell hyperplasia. As compared with calcitonin levels before thyroidectomy, a decrease of calcitonin greater than 50% 30 min after surgery was able to significantly distinguish patients who were cured from those who experienced persistence of disease. It was not possible to find a similar result when the decrease of calcitonin 10 min after surgery was considered. A rate of calcitonin decrease less than 50% 30 min after thyroidectomy plus central neck lymph node dissection suggests the persistence of tumor tissue in patients operated for MTC. These results indicate that intraoperative calcitonin monitoring may be a useful tool to predict the completeness of surgery in patients with MTC.
    The Journal of Clinical Endocrinology and Metabolism 09/2010; 95(9):E32-6. · 6.31 Impact Factor
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    ABSTRACT: Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C-cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)-stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery. Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy. A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0.002). PG-stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG-stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%. A CT cut-off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery.
    Clinical Endocrinology 07/2010; 73(1):85-8. · 3.40 Impact Factor