Thyroid Diseases: Avenia N

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.

Avenia N. · No affiliation provided · G Chir. · Pubmed #19505411 No free full text.

This publication has no abstract.

Moretti S, Barbi F, Tavano M, Calzolari F, Misso C, Lucchini R, Monacelli M, D'Ajello M, Puxeddu E, Avenia N. · Dipartimento di Medicina Interna, Centro di Riferimento Regionale per l'Endocrinochirurgia, Università degli Studi di Perugia, Perugia. · Chir Ital. · Pubmed #18689164 No free full text.

Abstract: Cancer originates from a single cell which, through the acquisition of mutations in genes for key growth and survival factors, undergoes clonal expansion. Study of the genome allowed the detection of genes whose mutation is involved in tumour formation. In detail, in most thyroid neoplasms we are now able to identify the genes which cause cancer initiation. Moreover, correlations between mutations and clinico-pathological features of the tumours have been revealed. Thus, the genetic study of tumours is not anymore only a scientific curiosity, but a useful tool for the formulation of the more efficacious therapeutic and follow-up strategies. In this review we will summarize the more recent molecular medicine acquisitions in the thyroid cancer field and will describe their present and eventually future impact on the activity of the endocrine surgeon.

Puxeddu E, Durante C, Avenia N, Filetti S, Russo D. · Department of Internal Medicine, University of Perugia, Via Enrico dal Pozzo, 06126 Perugia, Italy. · Trends Endocrinol Metab. · Pubmed #18337114 No free full text.

Abstract: Significant progress has recently been made in the clinical management of papillary thyroid carcinoma. The accuracy of diagnosis and prognostic stratification of this type of carcinoma are high but still fall below 100%. Lack of effective treatments for advanced stage papillary thyroid carcinoma leads to death in some patients. Approximately half of all such carcinomas harbor mutations in the gene encoding the serine/threonine-kinase B-type Raf kinase (BRAF), resulting in constitutive activation of the mitogen-activated protein kinase-extracellular-signal-regulated kinases signal transduction pathway. There is intriguing evidence that BRAF mutation testing of papillary thyroid carcinoma might improve the diagnosis, prognostic stratification and treatment of these tumors but large, prospective trials are needed to define the actual clinical impact of these approaches.

Pisaniello D, Parmeggiani D, Piatto A, Avenia N, d'Ajello M, Monacelli M, Calzolari F, Sanguinetti A, Parmeggiani U, Sperlongano P. · Dipartimento di Scienze Anestesiologiche, Chirurgiche e delle Emergenze, Seconda Università degli Studi di Napoli. · G Chir. · Pubmed #16371185 No free full text.

Abstract: Hypocalcemia is one of the most frequent complications after total extracapsular thyroidectomy (TET). In most of cases it is a transient phenomenon. The aim of this study is to evaluate if and how the oral administration of calcium or calcium combined with D-vitamin could effectively prevent post-thyroidectomy hypocalcemia. A randomized prospective study was performed, recruiting 120 patients who underwent total thyroidectomy. The patients in our series were randomly assigned to one of two groups: group A--patients who received calcium lactogluconate/calcium carbonate (mg 300 per day); group B--patients who received calcium carbonate/cholecalciferol therapy (calcium carbonate: 1500 mg per day; cholecalciferol 400 UI per day). The groups were well matched for age, sex and pathologies. Patients of both A and B groups were divided in two subgroups: those operated on for benign thyroid diseases (A1 and B1) and those operated on for malignancy (A2, B2). Serum calcium assays, performed 24, 48 and 72 hours after surgery, showed mean values of calcemia higher in patients of the B1 and B2 group. Statistical analysis was performed using a Student's t test. Mean serum calcium concentrations on post-operative day one, two and three were higher in patients of the group B (p<<0.01). Early and combined oral administration of both calcium and vitamin D seemed to prove major efficacy in preventing and treating post-operative hypocalcemia, showing mean serum calcium levels higher than those of patients who received only oral calcium administration. Nevertheless, further studies are necessary to validate these data.

Misso C, Calzolari F, Puxeddu E, Lucchini R, Monacelli M, D'Ajello F, Giammartino C, D'Ajello M, Ragusa M, Avenia N. · University of Perugia, Endocrine Surgical Unit. · G Chir. · Pubmed #19068183 No free full text.

Abstract: BACKGROUND: Medullary Thyroid Carcinoma (MTC) originates from the thyroid C cells and accounts for approximately 5-9% of all thyroid cancers. Aim of this study was to retrospectively evaluate the outcomes of 41 patients with MTC who underwent treatment at our institution. PATIENTS AND METHODS. We reviewed the records of 41 patients who underwent surgery between 1995 and 2004. The patients were divided into two groups: A) patients (n 30) without any previous surgery. B) patients (n 11) previously thyroidectomized and high calcitonin levels with or without radiological evidence of local regional or distant metastases. We performed total thyroidectomy with central compartment lymphadenectomy and ipsilateral modified radical neck dissection in group A patients. Group B patients underwent re-excision of the central neck compartment and bilateral modified radical neck dissection if it had not been previously performed. RESULTS: Most patients had major reduction in postoperative calcitonin levels. Compartmental dissection of the cervical node significantly improved the results of primary surgery and calcitonin returned to normal levels in approximately 60% of the patients in group A, but only the 30% of the patients in group B. CONCLUSIONS: The extent of the primary surgical resection and the evidence of local or distant metastases significantly influence the outcome of MTC patients. An extensive lymphadenectomy performed early in the treatment and re-operative cervical lymphadenectomy in patients with persistently high calcitonin levels after thyroidectomy significantly improved the outcome, although re-operation rarely results in normalized calcitonin levels and is associated with a higher incidence of complications.

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.

Lucchini R, Puxeddu E, Calzolari F, Burzelli F, Monacelli M, D'Ajello F, Macaluso R, Giammartino C, Ragusa M, De Feo P, Cavaliere A, Avenia N. · Inter-Hospital Functional Area of Endocrine Surgery, University of Perugia, Perugia, Italy. · Minerva Chir. · Pubmed #18607320 No free full text.

Abstract: AIM: Differentiated thyroid carcinomas (DTC) have a favourable outlook overall. Cornerstone of treatment is total thyroidectomy (TT), followed, if needed, by radiometabolic therapy. Such lesions however show a definite tendency to recur (about 35% of cases), generally in the first decade of follow-up: in 70% of patients such recurrence is local. Surgical resection is the only curative treatment option for local recurrence of well-differentiated thyroid cancer. Intraoperative ultrasonography (US) can be of significant help in facilitating localization and complete resection of lesions. The aim of the study was to review the authors' own experience with the use of such diagnostic method in the clinical setting of thyroid neoplasm recurrence. METHODS: Between January 2005 and March 2008 31 patients with DTC recurrences underwent intraoperative US exploration. Recurrences were easily identified and resected in all patients. Postoperative tireoglobuline (TG) was undetectable. RESULTS: In all 31 patients preoperative US confirmed the presence of the lesion. In 26 patients digital exploration of the surgical field did not yield a definitively positive finding, whereas in 5 the lesion was easily palpable. Intraoperative US revealed the presence of pathologic tissue in all cases, with examination time ranging from 4 to 14 minutes (median 8 minutes). In all cases surgical resection was complete, with pathologic confirmation of the sample, and no necessity to extend ablation. CONCLUSION: Intraoperative US can be of significant help in the identification of DTC recurrences, in particular when lesion dimensions are smaller than 10 mm in diameter and can facilitate a more radical excision of the tumor in a surgical field were anatomical landmarks can be altered by previous surgery and/or radiometabolic therapy.

Cavaliere A, Colella R, Puxeddu E, Gambelunghe G, Avenia N, d'Ajello M, Cartaginese F, Vitali R, Bellezza G, Giansanti M, Sidoni A, De Feo P. · Institute of Pathological Anatomy, Perugia University, Perugia, Italy. · J Endocrinol Invest. · Pubmed #18475047 No free full text.

Abstract: OBJECTIVE: Liquid-based cytology using the thin layer technique has recently been introduced in thyroid fine needle aspiration cytology together with or in substitution of direct smears, but its usefulness is still controversial and relatively few studies have been published in this field. The aim of the present study was to compare the results obtained from conventional smears with those from thin layer smears. DESIGN: In 3875 thyroid nodules, a double cytologic sampling was taken in randomized order, to prepare conventional or thin layer smears. MAIN OUTCOME: The diagnoses agreed in 2934 (75.7%) cases and disagreed in 941 (24.3%). The analysis of discordant data showed there were fewer non-diagnostic cases in the thin layer smears (377 vs 541, p<0.001) whereas in conventional smears there were more cases positive for carcinoma (27 vs 4, p<0.001). The cytohistologic correlation was available for 194 cases and showed that conventional smears had a greater capacity for revealing carcinomas (44 vs 31). Finally, diagnoses based on conventional smears were more sensitive than thin layer smears (93.6% vs 65.9%) whereas specificity was constant. CONCLUSIONS: From our experience, the conventional smear offers a greater possibility of diagnosis when suspecting malignancy or diagnosing malignancy cases, whereas thin layer smears significantly reduce the number of non-diagnostic cases. For this reason, we suggest combining the two techniques in routine cytologic diagnosis.

De Falco M, Oliva G, Ragusa M, Misso C, Parmeggiani D, Sperlongano P, Calzolari F, Puxeddu E, Misso C, Marzano LA, Barbarisi A, Parmeggiani U, Avenia N. · Second University of Naples, V Unit of Surgery and Advanced Surgical Procedures, Naples. · G Chir. · Pubmed #18419979 No free full text.

Abstract: INTRODUCTION: We carried out a retrospective analysis of our experience in the management of Differentiated Thyroid Carcinoma (DTC), in order to better define prognostic factors (age, gender, histological type, stage) and outline a standard procedure, where it's possible, for surgical treatment. PATIENTS AND METHODS: Patient population consisted of 432 cases, operated from 1978 to 2003. We carried out 285 operations of total thyroidectomy of which 39 associated to some kind of lymphadenectomy, 66 totalization (21 pts had been operated in other institutes), 60 subtotal thyroidectomies and 21 lobo-isthmectomies. Survival and mortality curves for age, sex, histological type, grading and staging have been calculated. Kaplan-Meyer statistical elaboration for disease-free interval and Mann-Whitney test for the comparison of different clinical and pathological data have been employed. RESULTS: The statistical analysis puts in evidence that on 432 cases examined, with a follow-up from 1 to 25 ys (median = 6.33 ys) and with a drop-out of 60 cases (13.8 %), total mortality for cancer has been of 24 cases (6,4%), with a median interval free by disease of 4.2 ys (range 5 months to 25 ys), and a probability to stay free by disease at 12 and 24 months respectively of 95.1% and 91.6%. The median survival is resulted of 5.8 ys (range 1 to 25 ys) with a probability of survival at 24 and 48 months respectively of 97.5% and 94.3%. The multivariate analysis evidences the most important variables, i.e. age > 45 ys, tumor of intermediate malignancy, with size 1.5 cm, operative M+, significantly condition the prognosis, noticeably getting worse it, independently by the kind of carried out operation. CONCLUSION: Our present therapeutic choices are: 1. total thyroidectomy in the treatment of the apparently benign pathology when bilaterally with spread; the checking at the final histological exam of a cancer makes however think adequate the carried out operation; 2. lobo-isthmectomy in the treatment of unilateral benign pathology or with suspect FNAB for follicular neoplasm; the histological checking of a cancer makes think the operation adequate only in presence of favourable prognostic parameters, but in presence even of just one unfavourable variable, we consider necessary the totalization; 3. total thyroidectomy in presence of a certain or strongly suspected preoperative diagnosis of cancer.

Prodosmo A, Giglio S, Moretti S, Mancini F, Barbi F, Avenia N, Di Conza G, Schünemann HJ, Pistola L, Ludovini V, Sacchi A, Pontecorvi A, Puxeddu E, Moretti F. · Lab. Molecular Oncogenesis, Regina Elena Cancer Institute, Rome, Italy. · J Mol Med. · Pubmed #18335186 links to  free full text

Abstract: A wild-type (wt) p53 gene characterizes thyroid tumors, except for the rare anaplastic histotype. Because p53 inactivation is a prerequisite for tumor development, alterations of p53 regulators represent an alternative way to impair p53 function. Indeed, murine double minute 2 (MDM2), the main p53 negative regulator, is overexpressed in many tumor histotypes including those of the thyroid. A new p53 regulator, MDM4 (a.k.a. MDMX or HDMX) an analog of MDM2, represents a new oncogene although its impact on tumor properties remains largely unexplored. We estimated levels of MDM2, MDM4, and its variants, MDM4-S (originally HDMX-S) and MDM4-211 (originally HDMX211), in a group of 57 papillary thyroid carcinomas (PTC), characterized by wt tumor protein 53, in comparison to matched contra-lateral lobe normal tissue. Further, we evaluated the association between expression levels of these genes and the histopathological features of tumors. Quantitative real-time polymerase chain reaction revealed a highly significant downregulation of MDM4 mRNA in tumor tissue compared to control tissue (P<0.0001), a finding confirmed by western blot on a subset of 20 tissue pairs. Moreover, the tumor-to-normal ratio of MDM4 levels for each individual was significantly lower in late tumor stages, suggesting a specific downregulation of MDM4 expression with tumor progression. In comparison, MDM2 messenger RNA (mRNA) and protein levels were frequently upregulated with no correlation with MDM4 levels. Lastly, we frequently detected overexpression of MDM4-S mRNA and presence of the aberrant form, MDM4-211 in this tumor group. These findings indicate that MDM4 alterations are a frequent event in PTC. It is worthy to note that the significant downregulation of full-length MDM4 in PTC reveals a novel status of this factor in human cancer that counsels careful evaluation of its role in human tumorigenesis and of its potential as therapeutic target.

Lucchini R, Puxeddu E, Calzolari F, Misso C, Monacelli M, Sanguinetti A, D'Ajello M, Avenia N. · Area Funzionale Omogenea Interaziendale di Endocrinochirurgia SC di Chirurgia Endocrina del Collo e dei Tessuti Molli, Centro di Riferimento Regionale, Università degli Studi di Perugia. · Chir Ital. · Pubmed #17663365 No free full text.

Abstract: Surgical resection is the only curative treatment option for local recurrence of well differentiated thyroid cancer. In our experience, we found that intraoperative ultrasonography can be of significant help in facilitating the localisation and complete resection of lesions. From 2005 to 2006, 12 patients with well differentiated thyroid tumour recurrences underwent intraoperative ultrasonography. Recurrences were easily identified and resected in all patients. Postoperative thyreoglobulin was not detected. Intraoperative ulrasonography can be of significant help in the identification of well differeniated thyroid tumour recurrences, particularly when the cancer is smaller than 10 mm in diameter, and can facilitate a more radical excision of the tumour.

Durante C, Puxeddu E, Ferretti E, Morisi R, Moretti S, Bruno R, Barbi F, Avenia N, Scipioni A, Verrienti A, Tosi E, Cavaliere A, Gulino A, Filetti S, Russo D. · Department of Clinical Sciences, University of Rome La Sapienza, 00161 Rome, Italy. · J Clin Endocrinol Metab. · Pubmed #17488796 links to  free full text

Abstract: CONTEXT: BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may influence the prognosis of these tumors. OBJECTIVE: Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs. DESIGN/SETTING AND PATIENTS: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry. RESULTS: mRNA levels for all thyroid-specific genes were reduced in all PTCs vs. normal thyroid tissues. NIS, AIT-B, Tg, and TPO expression was significantly lower in BRAF-mut tumors than in the BRAF-wt group. Glut-1 transcript levels were increased in all PTCs, and additional increases were noted in BRAF-mut tumors. In both tumor subsets, the NIS protein that was expressed was abnormally retained in the cytoplasm. CONCLUSION: BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism. This effect may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut PTCs.

Testini M, Rosato L, Avenia N, Basile F, Portincasa P, Piccinni G, Lissidini G, Biondi A, Gurrado A, Nacchiero M. · University of Bari, Bari, Italy. · Transplant Proc. · Pubmed #17275510 No free full text.

Abstract: BACKGROUND: We compared the surgical outcomes in patients undergoing bilateral thyroid surgery with or without parathyroid gland autotransplantation (PTAT). METHODS: One thousand three hundred nine patients underwent surgery for treatment of various thyroid diseases at three Academic Departments of General Surgery and one Endocrine-Surgical Unit throughout Italy. A nonviable gland or difficulties in dissection of the parathyroid glands were encountered in 160 (13.7%) patients. The subjects were divided into two groups: (1) patients undergoing PTAT during thyroidectomy (n = 79) versus (2) control group (n = 81), patients not undergoing PTAT. RESULTS: Clinical manifestations occurred in 5.0% of PTAT patients and in 13.6% of control patients (P = NS). Total postoperative hypocalcemia was less among PTAT than control patients (17.7% and 48.1%, respectively; P = .0001). There was no significant difference between the two groups in terms of definitive hypocalcemia (0% vs 2.5% in PTAT and control, respectively). Transient postoperative hypocalcemia was less among PTAT than controls (17.7% vs 45.7%; P = .0002). PTAT was associated with decreased occurrence of hypocalcemia in the two subgroups of patients operated for benign euthyroid disease (P < .0001), as compared with the control group. CONCLUSIONS: PTAT is an effective procedure to reduce the incidence of permanent hypoparathyroidism. Transient hypoparathyroidism appears to not be influenced by PTAT. Moreover, we observed that damage to one parathyroid gland has more side effects (ie, transient hypocalcemia) among patients who were preoperatively at low rather than at high risk of postoperative hypocalcemia.

Gambelunghe G, Fatone C, Ranchelli A, Fanelli C, Lucidi P, Cavaliere A, Avenia N, d'Ajello M, Santeusanio F, De Feo P. · Department of Internal Medicine, section of Internal Medicine and Metabolic and Endocrine diseases, University of Perugia, Perugia, Italy. · J Endocrinol Invest. · Pubmed #17114905 No free full text.

Abstract: This randomized controlled study was designed to test the efficacy and safety of percutaneous ultrasound (US)-guided laser photocoagulation (PLP) for treatment of subjects with compressive symptoms due to benign thyroid nodules and/or at high surgical risk. Twenty six subjects were randomized to the intervention (no. 13, age 68+/-3 yr, mean+/-SEM) or observation (no. 13, age 71+/-2 yr) groups. In the control group, the volume of nodules did not significantly change over the 30 week period of observation. In the intervention group, median nodule volume at baseline was 8.2 ml (range 2.8-26.9) and was not significantly different from that of the control group. Nodules decreased significantly (p<0.0001) by 22% after 2 weeks (6.5 ml; range 2.4-16.7) and by 44% after 30 weeks (4.6 ml; range 0.69-14.2). Energy given was correlated (p<0.05) with the reduction of thyroid nodule volume. All patients tolerated the treatment well and reported relief from compressive and cosmetic complaints (p<0.05). At the time of enrolment 7/13 (54%) and 6/13 (46%) of patients in the intervention and control groups, respectively, had sub clinical hyperthyroidism. PLP normalized thyroid function at 6 and 30 weeks after treatment. In conclusion, PLP is a promising safe and effective procedure for treatment of benign thyroid nodules in patients at high surgical risk.

Monacelli M, D'Ajello M, Calzolari F, Lucchini R, Misso C, Di Carlo L, Semeraro A, Daddi N, Sciamannini M, Lomonaco A, Avenia N. · Azienda Ospedaliera "S. Maria" di Terni, Area Funzionale Omogenea Interaziendale di Endocrinochirurgia del Collo e Tessuti Molli, Italy. · G Chir. · Pubmed #17064489 No free full text.

Abstract: INTRODUCTION: At present we are still debating on which is the most adequate therapeutic strategy concerning the size of the thyroidectomy and the extension of the lymphectomy in differentiated thyroid tumors. PATIENTS AND METHODS: From January 2000 to December 2005, 334 operations for thyroid neoplasms have been performed; 304 (91%) for differentiated tumors. In 124 cases (37%) the latero-cervical and/or the central compartment lymphectomy have been associated with thyroidectomy: 79 monolateral and central compartment lymphectomies (ML and CCL) (64%), 11 bilateral and central compartment lymphectomies (BL and CCL) (8%), and 34 central compartment lymphectomies (CCL) (28%) have been performed. RESULTS: Out of the 124 lymphectomies, in 44 cases (35.5%) we found the presence of metastasis in the lymph nodes of latero-cervical and central compartments, in 10 cases (8%) absence of metastasis in the lymph nodes of the latero-cervical and central compartments, in 25 cases (20%) presence of metastasis in the latero-cervical lymph nodes and absence of metastasis in the lymph nodes of the central compartment. In 11 cases of bilateral and central compartment lymphectomies, 5 of them (4%) had positive lymph nodes of the latero-cervical and central compartments, while the other, only 6 (5%), had positive latero-cervical lymph nodes on the same side as the neoplasia. In 34 central compartment lymphectomies there was absence of metastasis. Mortality rate was zero. There was one case (0.8%) of recurrent laryngeal nerve temporary bilateral palsy (RTBP); 4 cases (3.2%) of recurrent temporary monolateral palsy (RTMP); 2 cases (1.6%) of definitive monolateral palsy (DMP); 29 cases (23.5%) of temporary hypoparathyroidism (TH); 7 cases (5.5%) of definitive hypoparathyroidism (DH). CONCLUSIONS: Latero-cervical lymphectomy should be performed by necessity when clinical tests or pre-diagnostic exams show suspect lymph nodes, whereas central compartment lymphectomy should be performed in any case of thyroid neoplasia.

Lucchini R, Donetti D, D'Ajello M, Calzolari F, Pacchiarini D, Bolli L, Sanguinetti A, Puxeddu E, Monacelli M, Misso C, Gianmartino C, Macchitell L, Avenia N. · SC di Chirurgia Endocrina del Collo e Tessuti Molli, AO S. Maria, Terni. · Chir Ital. · Pubmed #16999150 No free full text.

Abstract: Diagnostic-therapeutic itineraries and treatment profiles are instruments of clinical management. The authors report on their experience with the experimental creation of such itineraries in thyroid nodular pathology. These are the fruit of collaboration between the management team, endocrinological surgeons, and the hospital computer staff. The drawing-up of guidelines in the hospital setting allows the systematic organisation of clinical activities to be accomplished in the health-care facility, quantifying costs for all diseases in order to be able to plan and implement changes in resources and staff utilisation. Application of the method, in addition, helps to develop a common language among hospital doctors and nurses, facilitates proper communication with patients, and ensures adequate patient information regarding the clinical itinerary the patient will have to take for his or her condition.

Monacelli M, Sperlongano P, D'Ajello M, Calzolari F, Piatto A, Lucchini R, Misso C, Parmeggiani D, Pisaniello D, Sordelli I, Sperlongano R, Avenia N. · Azienda Ospedaliera "Santa Maria", Terni. · G Chir. · Pubmed #16768871 No free full text.

Abstract: Differentiated thyroid cancer had an excellent prognosis; the diagnosis of sub-centimetric differentiated cancer (microcarcinoma) is more and more frequently. Clinical evolution of microcarcinoma could be various: microcarcinoma can represent an autoptic finding or can evolve with locoregional lymph node involvement or metastasis. Various clinical and genetic factors have been considered to predict the aggressiveness of this neoplasm. From 2001 to 2004, 74 patients with diagnosis of thyroid microcarcinoma underwent surgical treatment. By a retrospective survey we evaluated risk factors and the choice of surgical treatment. The aggressiveness appear to be related mainly to multifocality and size. Our therapeutic strategy is to perform total thyroidectomy for benign pathologies, total thyroidectomy with lymphadenectomy in cases with preoperative diagnosis of microcarcinoma.

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.

Fugazzola L, Puxeddu E, Avenia N, Romei C, Cirello V, Cavaliere A, Faviana P, Mannavola D, Moretti S, Rossi S, Sculli M, Bottici V, Beck-Peccoz P, Pacini F, Pinchera A, Santeusanio F, Elisei R. · Institute of Endocrine Sciences, University of Milan and Fondazione Policlinico IRCCS, Milan, Italy. · Endocr Relat Cancer. · Pubmed #16728573 links to  free full text

Abstract: Recently, a somatic point mutation of the B-RAF gene (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC), with a prevalence variable among different series. Since discordant data on the clinico-pathologic features of B-RAF mutated PTC are present in the literature, the aim of the present co-operative study was to establish the prevalence of this genetic alteration and to perform a genotype-phenotype correlation in a large cohort of patients with PTC. To this purpose, a series of 260 sporadic PTCs with different histological variants were included in the study. The mutational analysis of the B-RAF gene was performed either by RT-PCR followed by single-stranded conformational polymorphism or by PCR and direct sequencing. Statistical analyses were obtained by means of chi2/Fisher's exact test and t-test. Overall, a heterozygous T > A transversion at nucleotide 1799 (V600E) was found in 99 out of 260 PTCs (38%). According to the histological type of the tumor, the B-RAF (V600E) mutation was present in 48.3% of cases of classic PTCs (85 out of 176), in 17.6% (nine out of 51) of follicular variants of PTCs, in 21.7% (five out of 23) in other PTC variants and in none of the ten poorly differentiated tumors. B-RAF (V600E) was significantly associated with the classic variant of PTC (P = 0.0001) and with an older age at diagnosis (P = 0.01). No statistically significant correlation was found among the presence of B-RAF (V600E) and gender, tumor node metastasis (TNM), multicentricity of the tumor, stage at diagnosis and outcome. In conclusion, the present study reports the prevalence of B-RAF (V600E) (38%) in the largest series of sporadic PTCs, including 260 cases from three different Italian referring centers. This prevalence is similar to that calculated by pooling together all data previously reported, 39.6% (759 out of 1914 cases), thus indicating that the prevalence of this genetic event lies around 38-40%. Furthermore, B-RAF (V600E) was confirmed to be associated with the papillary growth pattern, but not with poorer differentiated PTC variants. A significant association of B-RAF mutation was also found with an older age at diagnosis, the mutation being very rare in childhood and adolescent PTCs. Finally, no correlation was found with a poorer prognosis and a worse outcome after a median follow-up of 72 months.

Sperlongano P, Parmeggiani D, Pisaniello D, De Falco M, Sordelli I, Accardo M, Cuccurullo V, Mansi L, Tartaro GP, Barbarisi A, Avenia N, Parmeggiani U. · Department of Anaesthesiological, Surgical and Emergency Sciences, Second University of Naples, Naples, Italy. · Front Biosci. · Pubmed #16720307 No free full text.

Abstract: A retrospective study was carried out to assessed reliability of the prognostic factors (histology, age, sex, and stage), and standard procedures for the surgical treatment of differentiated thyroid cancers (DTC). From the 144 DTC cases reviewed with follow-up ranging from 1 to 25 years (m = 6.33 years), total mortality for cancer was found to be 55% (8 patients), with a predictive positive value for recurrence of 95.4% and 91.8% at 12 and 24 months, respectively. Median survival was 8.8 years (range 1 to 25 years). The multivariate analysis showed that factors such as age > 45 years, histology of intermediate malignancy, size up to 1.5 cm, and presence of metastases, significantly worsened the prognosis, regardless of the intervention that was carried out. We suggest total thyroidectomy for the treatment of benign pathologies and confirmed or suspected cases of cancer. We reserve loboisthmectomy for the treatment of benign pathologies confined to one lobe or those with FNAB suggesting a follicular neoplasm.

Moretti S, Macchiarulo A, De Falco V, Avenia N, Barbi F, Carta C, Cavaliere A, Melillo RM, Passeri L, Santeusanio F, Tartaglia M, Santoro M, Puxeddu E. · Dipartimento di Medicina Interna, Università degli Studi di Perugia, Perugia, Italy. · Oncogene. · Pubmed #16501605 No free full text.

Abstract: Activating mutations of the BRAF gene are the most common genetic alterations in papillary thyroid carcinomas (PTCs) and the T1799A transversion, resulting in BRAFV600E, appeared virtually unique in this cancer type. Here, we report on the identification in a classic PTC of a novel BRAF mutation, namely a 1795GTT insertion, resulting in BRAFV599Ins, and describe its biochemical and molecular characterization. Kinase assays carried out on BRAFV599Ins and BRAFV600E revealed a three- to five-fold increase in the enzymatic activity of both mutants with respect to BRAFWT. Similarly, evaluation of BRAF-induced phosphorylation of MEK, MAPK and RSK revealed a significant MAPK cascade activation in cells expressing BRAFV599Ins or BRAFV600E, but not in cells expressing BRAFWT. Molecular dynamic simulations showed a destabilization of the inactive conformation of the enzyme in both BRAFV599Ins and BRAFV600E mutants, but not in BRAFWT. The analysis of the interaction energies inside the catalytic site allowed to demonstrate the presence of repulsive electrostatic forces acting on the activation loop and moving from inward to outward of the mutant enzymes. Finally, focus assays in NIH-3T3 cells confirmed a high transformation rate in the cells transfected either with BRAFV599Ins or BRAFV600E. In conclusion, this study demonstrated that BRAFV599Ins, as BRAFV600E, is a 'gain of function' mutation, characterized by a constitutive catalytic activation, which accounts for its causative role in the studied PTC.

Carta C, Moretti S, Passeri L, Barbi F, Avenia N, Cavaliere A, Monacelli M, Macchiarulo A, Santeusanio F, Tartaglia M, Puxeddu E. · Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy. · Clin Endocrinol (Oxf). · Pubmed #16402937 No free full text.

Abstract: OBJECTIVES: The genes RET and RAS, and more recently BRAF, have been shown to be frequently mutated in human papillary thyroid carcinomas (PTC). The aim of this study was to genotype for these mutations a cohort of thyroid tumours collected at our institutions. DESIGN AND PATIENTS: Thyroid tumours removed from 51 subjects were analysed, including 43 PTC and 8 non-PTC tumours [3 follicular adenomas (FA), 4 follicular carcinomas (FTC) and 1 anaplastic carcinoma (AC)]. MEASUREMENTS: RET/PTC1 and RET/PTC3 expression was evaluated by reverse transcriptase-polymerase chain reaction, whereas screening of BRAF (exon 15) and RAS (HRAS, KRAS2 and NRAS) mutations were performed, respectively, by single strand conformation polymorphism and denaturing high-pressure liquid chromatography. RESULTS: RET/PTC expressions was positive in 5/43 (11.6%) PTC and in none of the non-PTC tumour. Similarly, BRAF mutations were positive only in PTC, but with a higher prevalence (24/43 positives, 55.8%). All but one BRAF mutation resulted in the prototypic substitution of valine 600 with a glutamic acid. In one case, a somatic in-frame insertion of three bases at codon 599 resulted in the insertion of an additional valine. RET/PTC expression and BRAF mutations were mutually exclusive. Screening of the RAS gene allowed identification of oncogenic mutations in 1/3 (33.3%) FA and 3/4 (75%) FTC. None of the PTCs was positive for RAS. CONCLUSIONS: These data indicate that BRAF mutations are the most frequent genetic event in PTC and that RAS mutations, besides being a genetic hallmark of follicular tumours, are rare or completely absent in PTC from our area. Together, BRAF mutations and rarer RET rearrangements accounted for a genetic event in two-thirds of PTCs. This study showed a novel and presumably oncogenic mutation of BRAF, which is BRAF(V599Ins).

Parmeggiani U, Avenia N, De Falco M, Parmeggiani D, Pisaniello D, d'Ajello M, Monacelli M, Calzolari F, Sanguinetti A, Sperlongano P. · V Divisione di Chirurgia Generale e Techniche Chirurgiche Speciali, Dipartimento de Scienze Anestesiologiche, Chirurgiche e delle Emergenze, Seconda Università degli Studi di Napoli. · G Chir. · Pubmed #16371192 No free full text.

Abstract: In the present study the Authors tried and assess the advantages of the standard sutureless thyroidectomy performed by the Ligasure Vessel Sealing System, thanks to the use of the dedicated Precise handle. The Authors compared the efficacy of haemostasis and the economical impact of the device, in terms of drug administration and costs. The Authors comparatively analyzed 120 total extracapsular thyroidectomies (TET) performed by the standard operative technique (Group A, control) and 70 TET achieved by the "sutureless technique" (Group B, case). There was a statistically significant decrease of transient postoperative hypocalcemia (5.71% vs 7.5%) and also of mean operative time (about 20 minutes) in patients of the group B. Non significant decrease of other kind of complications (postoperative hemorrhage, transient and permanent inferior laryngeal palsy, stupor of the superior laryngeal nerve, seromas) were also observed. The use of the Ligasure Precise resulted easy, safe and efficient in the Authors' experience. It allowed the decrease of postoperative haemorrhages and mean operative time.