Francesca Marciello

Thyroid Nodules Treated with Percutaneous Radiofrequency Thermal Ablation: A Comparative Study

PURPOSE Percutaneous radiofrequency thermal ablation (RTA) was reported as an effective tool for the management of thyroid nodules (TNs). The aim of this study was to investigate the effects of RTA and to establish whether they were treatment-related by comparison with a matched, untreated control group. PATIENTS AND METHODS The study population included 40 patients with compressive TNs: 22 had nontoxic TNs, and 18 had toxic TNs and were treated with methimazole. In all patients, a fine-needle aspiration cytology was performed to exclude a thyroid malignancy. STUDY DESIGN Twenty patients were treated with RTA (group A), and 20 others did not receive any treatment (group B). At baseline, age, gender, and TN features did not differ significantly between groups. All patients were clinically, biochemically, and morphologically evaluated at baseline and after 1, 3, 6, and 12 months. RESULTS TN volume significantly decreased in group A (1.8 ± 0.3 ml at 12 months vs. 13.3 ± 1.8 ml at baseline; P < 0.0001) and remained stable in group B [11.7 ± 1.5 ml at 12 months vs. 11.2 ± 1.5 ml at baseline; P = not significant (NS)]. At 3-, 6-, and 12-month evaluations, TN volume was significantly lower in group A than in group B (P < 0.005). At the end of the follow-up, pressure symptoms were improved in all patients in group A but persisted unchanged in group B. In group A, hyperthyroidism completely recovered in 40% and improved in 40% of patients with toxic TNs, whereas it persisted in all patients with toxic TNs in group B. RTA was safe and well tolerated in all patients. CONCLUSIONS RTA induced a marked TN volume shrinkage resulting in parallel improvement of pressure symptoms. In most patients with toxic TNs, hyperthyroidism significantly improved as well. RTA may represent a valid therapeutic approach in patients with TNs not receiving conventional treatments.

Limitations of Chromogranin A in clinical practice

Context: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. Methods: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. Results: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. Conclusion: Serum CgA is not helpful for the first-line diagnosis of NEN.

Hepatic arterial embolization in patients with neuroendocrine tumors

Liver metastases occur in 46-93% of patients with neuroendocrine neoplasms (NENs). Presence and extension of liver metastases are considered important prognostic factors, as they may significantly impair the patient’s quality of life, because of either tumor bulk or hormonal hypersecretion. Therapies for NEN liver metastases include surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery is the gold standard for curative therapy, but in most of NEN patients with liver metastases, when surgery can not be applied, minimally invasive therapeutic approaches are adopted. They include trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), radiofrequency thermal ablation and new emerging techniques.TAE is based on selective infusion of particles in the branch of the hepatic artery supplying the tumor lesions. The goal of TAE is to occlude tumor blood vessels resulting in ischemia and necrosis. Many reports have shown that TAE can reduce tumor size and hormone output, resulting in palliation of symptoms without the use of cytotoxic drugs, resulting in better tolerability. This review will focus on TAE performance and safety in NEN patients with liver metastases.

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

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).

Low glycaemic diet and metformin therapy: a new approach in male subjects with acne resistant to common treatments

Acne is a common and complex skin disease, with a very complex pathogenesis. Although in women the relationship between acne and insulin resistance is well known, in particular in women with PCOS, in males this relationship has been poorly investigated. In total, 20 subjects with an altered metabolic profile were considered for this study and randomized as follows: 10 patients were treated with metformin plus a hypocaloric diet for 6 months (group A), while 10 patients did not receive any treatment with metformin and were only followed up (group B). All patients of group A, after 6 months of metformin therapy, had a statistically significant improvement compared with patients in group B. Our study reveals the importance of diet and insulin resistance in acne pathogenesis, and underlines the possible use of metformin and diet as possible adjuvant therapy for male patients with acne.

Teriparatide vs. Alendronate as a treatment for osteoporosis: Changes in biochemical markers of bone turnover, BMD and quality of life

Summary Background We studied the use of teriparatide in postmenopausal women with severe osteoporosis. Material/Methods Two groups (A and B) of patients affected by severe osteoporosis (T-score ⩽−2.5 at bone mineral density were analyzed and 2 vertebral fractures on radiograph). Group A was treated for 18 months with 20 μg/day of teriparatide. Group B was treated with bisphosphonates 70 mg/week. Every woman assumed 1 g of calcium and 800 IU of vitamin D3 daily. We evaluated the effects of therapy after 18 months (T18) from the beginning with bone turnover markers (alkaline phosphatase, procollagen type 1 N-terminal propeptide, and N-telopeptide cross-links) and dual-energy X-ray absorptiometry. Results Group A, at T18 procollagen type 1 N-terminal propeptide levels, increased 127%; bone alkaline phosphatase levels increased to 65%; N-telopeptide cross-links levels increased to 110%. Group B, at T18 procollagen type 1 N-terminal propeptide levels, decreased to 74%; bone alkaline phosphatase levels decreased to 41%; N-telopeptide cross-links levels decreased to 72%. After 18 months, lumbar bone mineral density increased to 12.4% and femoral bone mineral density increased to 5.2% in group A. Group B lumbar bone mineral density increased to 3.85% and femoral bone mineral density increased to 1.99%. Only a new vertebral fracture occurred in group A (2.4%), whereas 6 fractures occurred in group B (15.7%). The quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) revealed a significant improvement in daily living, performed domestic jobs, and locomotor function in groups A and B. Conclusions The use of rhPTH in patients with severe osteoporosis offers more protection against fractures and improves the QoL more than bisphosphonates.

Partitioning of Bronchopulmonary Carcinoids in Two Different Prognostic Categories by Ki-67 Score

Introduction: Histological distinction between typical and atypical bronchopulmonary carcinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid. Materials and Methods: The long-term post-surgical outcome of 106 radically treated patients affected by bronchopulmonary carcinoid from two Italian centers was correlated with tumor characteristics assessed by combining conventional histology with a panel of immunohistochemical markers of neuroendocrine differentiation (chromogranin-A, NSE) and proliferation activity (Ki-67 score). Results: Carcinoids were assessed as typical (TC = 75; 70.8%) and atypical (AC = 31; 29.2%). Mean follow-up was 8.3 years (range: 0–20; median: 8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid histotype (P = 0.003), tumor size (P = 0.012), mitotic index (P = 0.044), Ki-67 score (P < 0.0001), and synchronous node metastasis (P = 0.037). Of these, Cox multivariate analysis confirmed only Ki-67 score as independent predictor of disease recurrence (P = 0.009). The best cut-off for Ki-67 score (calculated by ROC curves) discriminating recurrent vs non-recurrent disease was 4% (sensitivity 79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients according to this cut-off, a significantly different disease-free survival was found (log-rank test P < 0.0001). Conclusion: Ki-67 score accurately separates bronchopulmonary carcinoids in two well-distinct histo-prognostic categories. Ki-67 score predicts the patients outcome better than mitotic count, histotype, and tumor stage and it is therefore helpful in establishing the appropriate follow-up.

Osteoporosis and Thyrotropin-Suppressive Therapy: Reduced Effectiveness of Alendronate

BACKGROUND Many reports of the effect of exogenous thyroxine therapy on bone mineral density (BMD) show a relationship between excess thyroid hormone administration and osteoporosis. The aim of this study was to evaluate the effect of antibone resorptive agents, in particular alendronate (ALN) on BMD in postmenopausal osteoporotic women with thyroid carcinoma who were receiving long-term thyrotropin (TSH)-suppressive therapy with thyroxine. METHODS Seventy-four postmenopausal women with low BMD (T-score < or =-2.5) and differentiated thyroid carcinoma on long-term TSH-suppressive therapy (TSH > or =0.05 and < or =0.1 microU/mL) for about 3-9 years were selected for the study. The patients were divided into three groups according to the length of levothyroxine (LT(4)) treatment prior to the beginning of the study: group A (TSH-suppressive therapy for about 3 years), group B (for about 6 years), and group C (for about 9 years). These patients were compared with 74 matched women not taking LT(4). All patients and controls were treated with bisphosphonates, calcium, and vitamin D for 2 years and evaluated. RESULTS After 24 months of treatment group A showed a 7.8% increase in lumbar BMD; group B, a 4.6% increase; and group C, a 0.86% increase. In the control group BMD increased 8.2%. A significant difference was found in both lumbar and femoral BMD increase among the three groups: group C had a lower BMD increase than group A (p < 0.001) and B (p < 0.001). CONCLUSIONS In postmenopausal women who were receiving adequate amounts of calcium and vitamin D in their diet ALN was less effective for those who were also receiving TSH-suppressive doses of LT(4) for either 6 or 9 years. The positive effect of ALN on BMD was less for longer periods of LT(4) treatment. It seems likely that other bisphosphonates would also be less effective in increasing BMD in postmenopausal women receiving TSH-suppressing doses of LT(4).

Targeted therapy with kinase inhibitors in aggressive endocrine tumors

Introduction: Kinase inhibitors (KIs) are a class of anticancer drugs that inhibit activity of the enzymes protein kinases, which regulate crucial cellular processes and have a demonstrated role in human oncogenesis. Treatment of advanced forms of endocrine cancer which are not responsive to cytotoxic chemotherapies is challenging and use of KIs is gaining a growing role in this field. Areas covered: The authors summarize the main genetic alterations known to be linked to endocrine tumors, indicating the rationale for utilizing KIs. Furthermore, they present an updated analysis of clinical trials available on PubMed Central, which were pertinent to the activities of KIs in aggressive endocrine cancer. The authors also discuss the adverse effects of KIs and summarize likely involved underlying mechanisms. Expert opinion: KIs are effective in obtaining a radiological disease control and an improvement of progression-free survival in several forms of endocrine cancer but will never deliver a knockout blow of the disease, due to mechanisms of adaptation to circumvent the specific molecular blockade. The new frontier of KIs treatment is to identify agents that could synergize activity of KIs. The true goal will be to perform an overall genotyping of each tumor, thus predicting the impact of combined targeted therapies in the context of a particular constellation of mutant genes.

Prognostic role of the CDNK1B V109G polymorphism in multiple endocrine neoplasia type 1.

CDKN1B encodes the cyclin‐dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype–phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow‐up data of tumour types and their severity were collected and associated with the genetic data. MEN1‐related aggressive and other malignant tumours of any origin were detected in 16.1% of wild‐type and 33.3% of polymorphism allele‐bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1.