Role of contrast-enhanced ultrasound to define prognosis and predict response to biotherapy in pancreatic neuroendocrine tumors.

PURPOSE: The incidence of neuroendocrine tumors (NETs) is progressively increasing. Most cases arise from the digestive system, where ileum, rectum and pancreas represent the commonest site of origin. Liver metastases are frequently detected at diagnosis or during the follow-up. Contrast-enhanced ultrasound (CEUS) is used in patients with pancreatic NETs (P-NETs) and liver metastases from P-NET but its role has not been standardized. The aim of this retrospective study was to investigate CEUS in patients with P-NETs and liver metastases from P-NET both as prognostic factor and predictor of response to therapy with somatostatin analogues (SSAs). METHODS: CEUS was performed at the diagnosis of NET and 3, 6 and 12 months after the beginning of SSAs. CEUS pattern was compared with contrast-enhanced computed tomography (CT) pattern. RESULTS: There was a significant association between CEUS and CT pattern (X 2 = 79.0; p < 0.0001). A significant association was found between CEUS pattern and Ki-67 index (X 2 = 24.6; p < 0.0001). The hypervascular homogeneous CEUS typical pattern was associated with low tumor grading (G1 or G2) (X 2 = 24.0; p < 0.0001). CEUS pattern changed from hypervascular homogeneous in baseline to hypovascular/hypervascular inhomogeneous after SSA therapy, with a significant association between tumor response at CT scan and appearance of hypervascular inhomogeneous pattern at CEUS evaluation (6 months: X 2 = 57.0; p < 0.0001; 12 months: X 2 = 49.8; p < 0.0001). CONCLUSIONS: In patients with P-NET, CEUS pattern correlates with tumor grading, being homogeneous in G1-G2 but not in G3 tumors. After therapy with SSAs, CEUS is predictive of response to SSAs. These findings seem to support a role of CEUS as prognostic and predictive factor of response.

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.

Short-term exposure to membrane-active antibiotics inhibits Cryptosporidium parvum infection in cell culture.

A cell culture system and double fluorogenic staining were used to study the susceptibility of Cryptosporidium parvum to membrane-active antibiotics. Buforin II and magainin II exerted a cytotoxic effect on sporozoites but did not consistently affect oocyst viability. Lasalocid and nigericin demonstrated less activity against sporozoites but reduced the infectivity of oocysts.