Thyroid Diseases: Pezzullo L

Rosato L, Miccoli P, Pinchera A, Lombardi G, Romano M, Avenia N, Bastagli A, Bellantone R, De Palma M, De Toma G, Gasparri G, Lampugnani R, Marini PL, Nasi PG, Pellizzo MR, Pezzullo L, Piccoli M, Testini M. · Dipartimento di Chirurgia - ASL TO/4, Ospedale di Ivrea, Italy. · G Chir. · Pubmed #19351456 No free full text.

Abstract: AIM: To review and to update the management protocols in thyroid surgery proposed two years ago by 1st Consensus Conference called on the topic by the Italian Association of Endocrine Surgery Units (UEC Club). METHOD: The 2nd Consensus Conference took place November 30, 2008 in Pisa within the framework of the 7th National Congress of the UEC Club. A selected board of endocrinologists and endocrine surgeons (chairmans: Paolo Miccoli and Aldo Pinchera; speaker: Lodovico Rosato) examined the individual chapters and submitted the consensus text for the approval of several experts. This plain and concise text provides the rationale of the thyroid patient management and wants to be the most complete possible tool for the physicians and other professionals in the field. CONCLUSIONS: The diagnostic, therapeutic and healthcare management protocols in thyroid surgery approved by the 2nd Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (UEC Club) and are subject to review by two years.

Milano A, Chiofalo MG, Basile M, Salzano de Luna A, Pezzullo L, Caponigro F. · National Tumor Institute of Naples, Fondazione G. Pascale, Via M. Semmola, 80131 Naples, Italy. · Anticancer Drugs. · Pubmed #16940797 No free full text.

Abstract: Carcinoma of the thyroid gland is the most common malignancy of the endocrine system. Differentiated tumors are often curable with surgical resection and radioactive iodine. A small percentage of such patients, however, do not undergo remission and need new therapeutic approaches. Both anaplastic and medullary thyroid carcinomas exhibit aggressive behavior and are usually resistant to current therapeutic modalities. Thyroid carcinoma represents a fascinating model and a particularly promising paradigm for targeted therapy because some of the key oncogenic events are activating mutations of genes coding for tyrosine kinases, and these occur early in cancer development. A prototype is the RET proto-oncogene, a receptor tyrosine kinase, which is a key regulator of development and a 'hotspot' for oncogenic mutations. Mutations in the RET proto-oncogene have been identified as causative for papillary carcinoma and familial medullary thyroid carcinoma, making it an attractive target for selective inhibition in these subtypes. ZD 6474 has shown promising activity in preclinical models against RET kinase, and its contemporary inhibition of vascular endothelial growth factor and epidermal growth factor pathways renders it a very attractive drug for clinical trials in thyroid cancer. Activating point mutation of B-RAF can occur early in the development of papillary carcinoma. Moreover, papillary carcinomas with these mutations have more aggressive properties and are diagnosed more often at an advanced stage. Clinical evaluation of B-RAF-targeting drugs is undergoing and trials in thyroid cancer are planned. Agents that restore radioiodine uptake, such as histone deacetylase inhibitors and retinoids, represent another exciting field in new drug development in thyroid cancer.

Calzolari F, Sartori PV, Talarico C, Parmeggiani D, Beretta E, Pezzullo L, Bovo G, Sperlongano P, Monacelli M, Lucchini R, Misso C, Gurrado A, D'Ajello M, Uggeri F, Puxeddu E, Nasi P, Testini M, Rosato L, Barbarisio A, Avenia N. · Inter-Hospital Functional Area of Endocrine Surgery, Umbria Region, Perugia, Italy. · Anticancer Res. · Pubmed #19031929 No free full text.

Abstract: BACKGROUND: Intrathyroid metastases (ITM) are rare and usually have a dismal prognosis. The aim of this study was to detect which neoplasms metastasize most often to the thyroid gland, their clinical features and treatment options. MATERIALS AND METHODS: Retrospective analysis of clinical files of 17,122 patients submitted to surgery for thyroid disease between 1995 and 2005. Twenty-five patients (median age 61 years) were affected by ITM. RESULTS: The site of the primary tumor was: kidney (15), lung (4), colon (3), breast (1), melanoma (1), and unknown in 1 patient. Ten patients (40%) complained of preoperative symptoms, in the others, thyroid involvement was incidentally discovered during the follow-up for the primary cancer. Twenty patients (80%) underwent total thyroidectomy, 3 received thyroid lobectomy and 2 palliative procedures. Morbidity was 16%, mortality was nil. The median follow-up was 24 months. CONCLUSION: ITM should always be suspected in any patient with a previous history of malignancy. Fine-needle agobiopsy (FNAB) with immunohistochemical stains may help in preoperative workup. A long delay between the primary tumor and the recurrence warrants surgery and total thyroidectomy seems to be the treatment of choice because of the multifocality of metastasis to the thyroid gland.

Faggiano A, Grimaldi F, Pezzullo L, Chiofalo MG, Caracò C, Mozzillo N, Angeletti G, Santeusanio F, Lombardi G, Colao A, Avenia N, Ferolla P. · Department of Molecular and Clinical Endocrinology and Oncology, University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy. · Endocr Relat Cancer. · Pubmed #19004986 No free full text.

Abstract: In patients with postoperative persistent medullary thyroid cancer (MTC), the tumor detection rate is generally low for most of the imaging techniques now available. The aim of this study was to investigate if the clinico-biological profile of the tumor may indicate which imaging technique to perform in order to identify postoperative persistent or relapsing MTC foci. Thirty-five consecutive MTC patients with detectable and progressively increasing postoperative serum concentrations of calcitonin were enrolled in the study. The detection rates of 18F-deoxy-d-glucose (FDG)-positron emission tomography (PET), somatostatin receptor scintigraphy (SRS), and 131I-metaiodobenzylguanidine scintigraphy (MIBG) were compared in relation with calcitonin and carcinoembryonic antigen serum concentrations, Ki-67 score and results of conventional imaging techniques (CIT). FDG-PET positivity was significantly associated with calcitonin serum concentrations >400 pg/ml and Ki-67 score >2.0% (P<0.05), while SRS positivity was associated with calcitonin serum concentrations >800 pg/ml (P<0.05). SRS positivity significantly correlated with tumor appearance at CIT (P<0.01), while FDG-PET was positive in nine CIT-negative patients. The secretive and proliferative tumor profile may guide the choice of the imaging technique to use in the follow-up of patients with MTC. A Ki-67 score >2.0% suggests to perform a FDG-PET in addition to conventional imaging. Calcitonin secretion predicts both FDG-PET and SRS uptake but SRS positivity is generally found only in patients with well defined MTC lesions that are also detectable at the conventional imaging examination. MIBG outcome is not predicted by any clinico-biological factors here investigated.

Chiappetta G, Ferraro A, Vuttariello E, Monaco M, Galdiero F, De Simone V, Califano D, Pallante P, Botti G, Pezzullo L, Pierantoni GM, Santoro M, Fusco A. · Istituto Nazionale dei Tumori, Fondazione Pascale, via Mariano Semmola, 80131 Naples, Italy. · Eur J Cancer. · Pubmed #18375116 No free full text.

Abstract: We have analysed the expression of the HMGA2 gene in a panel of normal and neoplastic thyroid tissues by immunohistochemistry and quantitative RT-PCR. HMGA2 protein was detectable in four out of 21 follicular carcinomas, 30 out of 45 papillary carcinomas, and 11 out of 12 undifferentiated carcinomas. As far as follicular thyroid adenomas are concerned, only three cases of the 31 analysed showed HMGA2 protein expression, whereas it was absent in seven normal thyroid tissues and in 12 hyperplastic nodules. Quantitative RT-PCR showed that almost all the papillary thyroid carcinomas and 13 out of 16 follicular thyroid carcinomas express much higher HMGA2 specific mRNA levels in comparison to normal thyroids and adenomas. Therefore, our data support the quantitative RT-PCR analysis of HMGA2 expression, rather than immunohistochemistry, as a powerful tool for the diagnosis of thyroid neoplasias.

Chiofalo MG, Misso C, Insabato L, Lastoria S, Pezzullo L. · Department of Surgical Oncology, National Cancer Institute, Naples, Italy. · Endocr Pract. · Pubmed #17599859 No free full text.

Abstract: OBJECTIVE: To report an unusual case of persistent thyrotoxicosis after treatment of Graves' disease, because of coexistence of struma ovarii. METHODS: We report the clinical history, imaging studies, laboratory and pathologic data, and treatment in a patient with persistent hyperthyroidism after surgical treatment of Graves' disease. In addition, we discuss some aspects of the pathogenesis of hyperthyroidism due to functioning struma ovarii. RESULTS: A 42-year-old woman underwent near-total thyroidectomy for treatment of Graves' disease. Post-operatively, hyperthyroidism was still present. Methimazole was administered again, and performance of a 131I whole-body scan demonstrated a focus of intense uptake in the pelvis. Pelvic ultrasonography revealed a mass (11 by 8 by 7.1 cm) arising from the right ovary, with both solid and cystic components. Abdominal surgical exploration was performed, and the final histologic diagnosis was struma ovarii. The symptoms of hyperthyroidism diminished, and 3 weeks postoperatively, the thyroid hormone levels were in the hypothyroid range. CONCLUSION: In patients with refractory hyperthyroidism after thyroid surgical treatment, radioiodine scanning should be performed to diagnose or exclude the functioning profile of ovarian masses.

Chiappetta G, Ammirante M, Basile A, Rosati A, Festa M, Monaco M, Vuttariello E, Pasquinelli R, Arra C, Zerilli M, Todaro M, Stassi G, Pezzullo L, Gentilella A, Tosco A, Pascale M, Marzullo L, Belisario MA, Turco MC, Leone A. · Dipartimento di Scienze Farmaceutiche (DiFarma), University of Salerno, Via ponte don Melillo, 84084 Fisciano, Italy. · J Clin Endocrinol Metab. · Pubmed #17164298 links to  free full text

Abstract: CONTEXT: We previously showed that BAG3 protein, a member of the BAG (Bcl-2-associated athanogene) co-chaperone family, modulates apoptosis in human leukemias. The expression of BAG3 in other tumor types has not been extensively investigated so far. OBJECTIVE: The objective of this study was to analyze BAG3 expression in thyroid neoplastic cells and investigate its influence in cell apoptotic response to TNF-related apoptosis-inducing ligand (TRAIL). DESIGN, SETTING, AND PATIENTS: We investigated BAG3 expression in human thyroid carcinoma cell lines, including NPA, and the effect of BAG3-specific small interfering RNA on TRAIL-induced apoptosis in NPA cells. Subsequently, we analyzed BAG3 expression in 30 benign lesions and 56 carcinomas from patients of the Naples Tumor Institute Fondazione Senatore Pascale. MAIN OUTCOME MEASURES: The main outcome measures were: analysis of BAG3 protein in NPA cells by Western blot and immunocytochemistry; analysis of apoptosis in TRAIL-stimulated NPA cells by flow cytometry; and evaluation of BAG3 expression in specimens from thyroid lesions by immunohistochemistry. RESULTS: BAG3 was expressed in human thyroid carcinoma cell lines; small interfering RNA-mediated downmodulation of its levels significantly (P < 0.0195) enhanced NPA cell apoptotic response to TRAIL. The protein was not detectable in 19 of 20 specimens of normal thyroid or goiters, whereas 54 of 56 analyzed carcinomas (15 follicular, 28 papillary, and 13 anaplastic) were clearly positive for BAG3 expression. CONCLUSIONS: BAG3 downmodulates the apoptotic response to TRAIL in human neoplastic thyroid cells. The protein is specifically expressed in thyroid carcinomas and not in normal thyroid tissue or goiter.

Chiofalo MG, Cappabianca P, Del Basso De Caro ML, Pezzullo L. · Department of Surgical Oncology, National Cancer Institute, Via S Caterina da Siena 78, 80132, Naples, Italy. · J Neurooncol. · Pubmed #17021955 No free full text.

Abstract: A 46-year-old female patient with previously recognized Graves' ophthalmopathy, underwent total thyroidectomy. After thyroid surgery exophthalmos worsened and signs unsteadiness of gait appeared. Magnetic resonance imaging showed a lesion in the basal portion of the left cerebellar hemisphere. Therefore, the patient underwent surgery. Pathological examination revealed dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease).

Anonymous00050, Rosato L, Pinchera A, Bellastella A, De Antoni E, Martino E, Miccoli P, Pontecorvi A, Torre G, Vitti P, Pelizzo MR, Avenia N, Nasi PG, Bellantone R, Lampugnani R, De Palma M, Pezzullo L, Ardito G, De Toma G. · S.C. di Chirurgia, UEC, Ospedale di Ivrea. · Chir Ital. · Pubmed #16734162 No free full text.

Abstract: The aim of the study was to draw up a management protocol in thyroid surgery promoted by the Italian Association of Endocrine Surgery Units (Club delle UEC), shared by the experts and applied by the operators in the sector. The management protocols already presented in February 2002 and drawn up by the first Author of the present publication on the occasion of the current review were examined by the I Consensus Conference called on the topic by the Italian Endocrine Surgery Units. The conference comprised two distinct sessions, the first on 18 June 2005 within the framework of the 4th National Congress of the Club delle UEC in Naples, and the second on 17 September 2005 within the framework of the 8th Multidisciplinary Scanno Prize Meeting. A selected board of endocrinologists and endocrine surgeons, chaired by Aldo Pinchera and comprising the first nine Authors of this paper, examined the individual chapters in close collaboration with the other Authors, comparing their findings with the opinions of the experts cited in the text and submitting the consensus text for the approval of all those present. The diagnostic, therapeutic and healtcare management protocols in thyroid surgery approved by the I Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (Club delle UEC) and are subject to review by October 1, 2007.

Motti ML, Califano D, Troncone G, De Marco C, Migliaccio I, Palmieri E, Pezzullo L, Palombini L, Fusco A, Viglietto G. · Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy. · Am J Pathol. · Pubmed #15743786 links to  free full text

Abstract: Functional inactivation of the tumor suppressor p27(kip1) in human cancer occurs either through loss of expression or through phosphorylation-dependent cytoplasmic sequestration. Here we demonstrate that dysregulation of the PI3K/AKT pathway is important in thyroid carcinogenesis and that p27(kip1) is a key target of the growth-regulatory activity exerted by this pathway in thyroid cancer cells. Using specific PI3K inhibitors (LY294002, wortmannin, and PTEN) and a dominant active AKT construct (myrAKT), we demonstrated that the PI3K/AKT pathway controlled thyroid cell proliferation by regulating the expression and subcellular localization of p27. Results obtained with phospho-specific antibodies and with transfection of nonphosphorylable p27(kip1) mutant constructs demonstrated that PI3K/AKT-dependent regulation of p27(kip1) mislocalization in thyroid cancer cells occurred via phosphorylation of p27(kip1) at T157 and T198 (but not at S10 or T187). Finally, we evaluated whether these results were applicable to human tumors. Analysis of 100 thyroid carcinomas indicated that p27(kip1) phosphorylation at T157/T198 and cytoplasmic mislocalization were preferentially associated with activation of the PI3K/AKT pathway. Thus the PI3/AKT pathway and its effector p27(kip1) play major roles in thyroid carcinogenesis.

Chiappetta G, Pentimalli F, Monaco M, Fedele M, Pasquinelli R, Pierantoni GM, Ribecco MT, Santelli G, Califano D, Pezzullo L, Fusco A. · Istituto dei Tumori di Napoli, Napoli, Italy. · Oncol Rep. · Pubmed #15254683 No free full text.

Abstract: Overexpression of thymosin beta-10 (TB10) has been shown in rat thyroid transformed cell lines, and in human thyroid carcinoma tissues and cell lines. To investigate whether TB10 detection could be a valid tool in the diagnosis of human thyroid neoplasias, we extended the analysis of TB10 expression to a large number of thyroid hyperproliferative and neoplastic tissues using an immunohistochemical assay. Our analyses showed a TB10 positive staining in all human thyroid carcinomas particularly in the anaplastic histotypes, whereas no TB10 immunostaining was observed in normal thyroid, in adenomas and the majority of the goiters. These results suggest that the evaluation of TB10 gene expression may be considered a promising means of diagnosis of human thyroid hyperproliferative disorders.

Rosato L, Avenia N, Bernante P, De Palma M, Gulino G, Nasi PG, Pelizzo MR, Pezzullo L. · Department of Surgery, Endocrine Surgical Unit, Ivrea Hospital, Piazza della Credenza, 2-10015 Ivrea, Italy. · World J Surg. · Pubmed #14961204 No free full text.

Abstract: Complication rates associated with thyroid surgery can be evaluated only through analysis of case studies and follow-up data. This study covers postoperative data from 14,934 patients subjected to a follow-up of 5 years. Among them, 3130 (20.9%) underwent total lobectomy (TL), 9599 (64.3%) total thyroidectomy (TT), 1448 (9.7%) subtotal thyroidectomy with a monolateral remnant (MRST), and 757 (5.1%) subtotal thyroidectomy with bilateral remnants (BRST). A total of 6% of the patients had already been operated on. Persistent hypoparathyroidism occurred after 1.7% of all the operations, and temporary hypoparathyroidism was noted in 8.3%. Permanent palsy of the laryngeal recurrent nerve (LRN) occurred in 1.0% of patients, transient palsy in 2.0%, and diplegia in 0.4%. The superior laryngeal nerve was damaged in 3.7%; dysphagia occurred in 1.4% of cases, hemorrhage in 1.2%, and wound infection in 0.3%. No deaths were reported. A significant rate of LRN damage was noted, which has an important impact on the patient's social life. Hypoparathyroidism after total thyroidectomy is an important complication that can be successfully treated by therapy, although it is not always easily managed in special circumstances such as in young persons or pregnant women. The complications associated with thyroid surgery must be kept in mind so the surgeon can carefully evaluate the surgical and medical therapeutic options, have more precise surgical indications, and be able to give the patient adequate information.

Pezzullo L, Chiofalo MG, Losito NS, Caracò C, Marone U, Mozzillo N. · Divisione di Oncologia Chirurgica B, Istituto Nazionale Tumori, Napoli. · Tumori. · Pubmed #12903621 No free full text.

Abstract: Parathyroid carcinoma is a rare malignancy. We report the case of a 66 years old man referred to our department for a large substernal goiter suspected as a thyroid cancer associated with severe hyperparathyroidism. After normalization of serum levels of calcemia, total thyroidectomy and subtotal parathyroidectomy was performed. Histopathology revealed a parathyroid cancer of 450 g.

Rosato L, Avenia N, De Palma M, Gulino G, Nasi PG, Pezzullo L. · S.C. di Chirurgia, Modulo di Endocrinochirurgia, Ospedale di Ivrea. · Chir Ital. · Pubmed #12469460 No free full text.

Abstract: The range of indications for total thyroidectomy in the treatment of thyroid disease is steadily increasing, but any attempt to assess its real efficacy necessarily calls for a knowledge of the incidence of complications, amongst other things in order to provide the patient with complete information regarding the operation before obtaining his or her consent. Retrospective and observational analysis of 14,934 thyroidectomies performed in 42 Endocrine Surgery Units in Italy has made it possible to compare total thyroidectomy (TT) versus subtotal thyroidectomy with a bilateral remnant (ST-BR), subtotal thyroidectomy with a unilateral remnant (ST-UR) and total lobectomy-isthmectomy (TLI). The correlation between the number of total thyroidectomies and each of the other surgical procedures and the number of complications occurring with each of them was also assessed in order to quantify the effective risk of complications by determining the Odds Ratios on the basis of univariate analysis of the variables considered. The cases reviewed consisted of 9,599 TT (64%), 3,130 TLI (21%), 1,448 ST-UR (22%) and 757 ST-BR (5%); 13,023 (87%) cases were suffering from benign disease and 1,911 (13%) from malignancies. Recurrent laryngeal nerve injuries were present in 4.3% of the TT cases with 2.4% transient and 1.3% definitive (as against 3% in ST-BR and 2% in ST-UR with 1.4% and 1.1% transient, and 1% and 0.6% definitive, respectively; and 1.4% transient and 0.6% definitive in TLI). Hypocalcaemia after TT was transient in 14% and definitive in 2.2% (as against transient rates of 5% in ST-BR and ST-UR and 0.4 in TLI; and definitive hypocalcaemia in 0.6%, 0.8% and 0.07%, respectively). Haemorrhage occurred in 1.6% of TT cases (as against 2.1%, 0.5% and 0.4% in ST-BR, ST-UR and TLI, respectively). The Odds Ratios showed that TT presented a 16% higher complication rate than ST-UR which was assigned a value of 1, a 3% higher rate than ST-BR and a 5% lower rate than TLI. This greater incidence of complications with TT is attributable mainly to the greater incidence of transient hypoglycaemia and to a lesser extent to the slightly higher incidence of definitive hypoglycaemia, whereas the incidences of recurrent laryngeal nerve injuries were very similar in TT and ST-BR. Haemorrhagic complications were more frequent in ST-BR than in TT. Bearing in mind that TT is the absolute indication in the more demanding thyroid diseases (tumours, retrosternal goitre, Basedow's disease, recurrences) and in view of its fairly low complication rate, we believe that TT is a safe, reliable procedure, provided it is performed in a technically scrupulous manner. ST-BR is a technique which should be abandoned owing to the fact that its complication rate is comparable to that of TT and to the recurrences it may give rise to. ST-UR may be indicated if the surgeon is not sure of safeguarding the anatomical integrity of the recurrent nerve on one side.

Montella M, Pezzullo L, Crispo A, Izzo F, Amore A, Marone U, Tamburini M, Ronga D, Chiofalo MG, Chiappetta G, Mozzillo N. · Unit of Epidemiology, National Cancer Institute, G. Pascale Foundation, Via M. Semmola, Naples, Italy. · Oncol Rep. · Pubmed #12469158 No free full text.

Abstract: Some studies report an increased risk of autoimmune thyroid disease in hepatitis C and B as well as in interferon therapy. Recently a new link between HCV and papillary thyroid cancer has been published. The mechanism responsible for the oncogenetic role of HCV is not well understood, but it involves immunity system and autoimmunity disorders. We designed a case-control study on HCV exposure. To assess the positivity to HCV ELISA test and polymerize chain reaction technique (PCR) were used. For statistical analysis an odds ratio and corresponding 95% confidence intervals were computed using unconditional multiple-logistic-regression models. Our findings show a statistically significant association between HCV and papillary thyroid cancer (OR = 3.3, 95% CI 1.5-7.4, p=0.003), overall in female gender (OR = 3.3, 95% CI 1.2-8.7, p=0.01) and in the > or =50 years age category the risk for thyroid cancer was confirmed by the OR = 3.2 (95% CI 1.3-7.9, p=0.01). Based on our study there is an association between HCV and thyroid cancer and it is more readily detectable in countries with a high prevalence of HCV.

Chiofalo MG, Corazzelli G, Franco R, De Chiara A, Pezzullo L. · No affiliation provided · J Endocrinol Invest. · Pubmed #18852536 No free full text.

This publication has no abstract.

Montella M, Crispo A, Pezzullo L, Izzo F, Fabbrocini G, Ronga D, Tamburini M. · No affiliation provided · Int J Cancer. · Pubmed #10918206 No free full text.

This publication has no abstract.