Total thyroidectomy for Graves' disease treatment.

OBJECTIVES: Graves' disease (GD) is the most common cause of hyperthyroidism, and accounts worldwide for 60-80% of all cases. The diagnosis is based on clinical findings, and is confirmed by the presence of TRAB, suppression of TSH, and elevation of free thyroxin (free T4), and triiodinethyronin (free T3). GD can be treated by antithyroid drugs, radioactive iodine, or surgery. The aim of this study was to review retrospectively the surgical management, in terms of safety and efficacy, in 50 patients operated in the Department of Surgical Sciences since 2005 through 2010 and followed up at the Endocrinology Unit A of the Experimental Medicine Department. We assessed postoperative complications, which included the presence, persistence and development of ophthalmopathy, transient hypocalcemia, permanent hypoparathyroidism and recurrent laryngeal nerve palsy. MATERIALS AND METHODS: We analyzed data from 50 patients with GD who were eligible and underwent Total Thyroidectomy (TT). Thirty-nine patients underwent TT for recurrent hyperthyroidism after medical therapy and eleven patients for severe ophtalmopathy. The mean follow up was 41 months (range: 10-70). RESULTS: Eleven patients had ophtalmopathy before surgery. Four patients developed an ophtalmopathy after surgery. Eleven patients presented hypocalcemia, transient in ten patients and permanent in one patient. Five patients developed a transient disphony. Conclusions. Total thyroidectomy is a safe and radical procedure in Graves' disease treatment. Complications of TT are not different than subtotal thyroidectomy if it's performed by expert surgeons.

Difficulties in the diagnosis of thyroid paraganglioma: a clinical case.

Thyroid Paragangliomas are exceptionally rare tumors and only 35 documented cases have been reported in the literature. We report an additional unusual male case of thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma. A 45-year-old man presented with a solitary thyroid nodule. Physical examination revealed a smooth, well-circumscribed, firm, mobile, painless thyroid nodule in the right lobe measuring 3 cm. Ultrasound examination showed a 40 mm hypoechoic, non-homogeneous nodule with peri- and intra-nodular vascular flow. An ultrasound-guided fine needle aspiration biopsy was performed showing the presence of atypical cells (Thy 3). He underwent a total thyroidectomy associated to VI level lymphectomy. Histology showed a thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma measuring 0.3 cm in the greatest dimension. Thyroid Paraganglioma is an elusive tumor. It is difficult to diagnose and should be included in the differential diagnosis of all neuroendocrine tumors of the thyroid, even those arising in men or behaving in a locally aggressive fashion.

Diagnostic utility of thyroglobulin measurement in the fine needle aspirates from cervical lymph nodes: a case report.

Fine needle aspiration cytology (FNAC) is the more accurate diagnostic method for cervical lymph node (CLN) metastasis from differentiated thyroid cancers (DTC). However, FNAC diagnosis of cystic CLN is, in most cases, uninformative due to inadequate cellularity. Recently, thyroglobulin (Tg) detection in FNAC needle washout fluid has been shown to improve the diagnostic accuracy of FNAC, and its routine association with cytology is recommended. We here describe the case of a 20 yr old girl complaining of the recent appearance of palpable non-painful laterocervical nodes in the neck. Ultrasound examination revealed the presence of 3 cystic CLNs and 2 mixed thyroid nodules, with the larger one showing irregular margins. On the latter, and on 2 larger CLNs, FNAC was performed, and both Tg protein and mRNA were determined in the needle washout. The cytological analysis was not diagnostic for the two CLNs, while that of the thyroid nodule reported the presence of colloid and groups of thyrocytes with normal morphology. Both CLNs showed, however, high levels of Tg protein and were positive for Tg mRNA, suggestive of metastatic DTC. Based on these findings, the FNAC analysis was performed on the second smaller thyroid nodule suggesting (Tir4) the presence of PTC. The patient was then subjected to total thyroidectomy with lymph nodes resection of the central and homolateral compartments. The histological diagnosis confirmed the presence of a PTC in the small nodule and metastatic lymph nodes. In conclusion, this case confirms that the cytological diagnosis of cystic lymph nodes is challenging, and that the measurement of Tg protein and/or mRNA in the needle washout may overcome this limitation.

Surgical strategies in patients with medullary thyroid carcinoma.

OBJECTIVES: Aim of the study was to identify, in 59 operated patients affected by medullary thyroid carcinoma (MTC), the recurrence rate, survival, mortality and incidences of surgically derived hypoparathyroidism and recurrent laryngeal nerve injury (RLNI). MATERIALS AND METHODS: Based on pre-surgical diagnosis of the 59 patients included in the study, 35 underwent total thyroidectomy with central neck dissection (Group A), 14 total thyroidectomy, central neck dissection and monolateral functional neck dissection (Group B) and 10 total thyroidectomy central neck dissection, bilateral functional neck dissection (Group C). Overall survival, recurrences, incidence of hypoparathyroidism and RLNI were evaluated. RESULTS: The survival and recurrences were not statistically different among the three Groups. In Group B there was major probability of re-operation (p=0.042). The mortality rate was clearly major in Group C (p=0.003) due to the stage of pathology. Group C showed a high number of hypoparatiroidism compared to Group B, and B compared to A. In Group A there was only one unexpected RLNI; in 5 cases, 3 in Group B and 2 in Group C, there were a necessity laringeal section due to nerve tumor involvement. CONCLUSIONS: From our data it appears clearly that disease outcome following the different surgical approaches is mainly determinated by the stage of the disease at diagnosis. However, the finding that patients in Group A and B showed a high rate of local-regional recurrences may suggest that homolateral lymphadenectomy in Group A patients and bilateral lymphadenectomy in Group B patients should be always performed.

Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines.

OBJECTIVES: Anaplastic thyroid carcinomas (ATC) are highly aggressive tumours unresponsive to any available radio- or chemotherapeutic protocol, with a median survival rate of 4-5 months from the time of diagnosis. We previously demonstrated that ATC are characterized by increased expression of the kinases Aurora-A, -B and -C, involved in the regulation of multiple steps of the mitotic phase. In this study, the in vitro effects of SNS-314 mesylate, a pan-inhibitor of the Aurora kinases, on growth and tumorigenicity of ATC cells were evaluated. MATERIALS AND METHODS: The effects of SNS-314 mesylate were assessed on the ATC derived cell lines CAL-62, 8305C, 8505C and BHT-101 by means of cell proliferation assay, immunofluorescence, cytofluorimetry, time lapse microscopy, and colony formation in soft agar. RESULTS: Treatment of the different ATC cells with SNS-314 mesylate inhibited proliferation in a time- and dose-dependent manner, with IC(50) comprised between 2.6 nM and 26.6 nM. CAL-62 cells exposed for 24 h to SNS-314 mesylate 100 nM evidenced a significant augmentation of the apoptotic index. Time-lapse video-microscopy of CAL-62 cells showed that SNS-314 mesylate prevents the completion of mitosis leading to polyploidy. Western blot experiments demonstrated that the auto-phosphorylation of the Aurora kinases as well as histone H3 phosphorylation in CAL-62 treated cells was inhibited. Finally, the drug inhibited colony formation in soft agar of all cell lines. CONCLUSIONS: Our results demonstrated that SNS-314 mesylate is capable to efficiently reduce cell growth and tumorigenicity of different ATC derived cell lines suggesting its potential therapeutic value for ATC treatment.

Aurora kinases: new molecular targets in thyroid cancer therapy.

Genetic instability, a hallmark of solid tumors including thyroid cancers, is thought to represent the mean by which premalignant cells acquire novel functional capabilities responsible for cancer cell growth and tumour progression. Over the last few years, the knowledge of the molecular processes controlling the mitotic phase of the cell cycle has increased considerably, and different mitotic proteins, whose expression or function has been found altered in human cancer tissues, have been associated to tumour genetic instability and aneuploidy. These include the three members of the Aurora kinase family (Aurora-A, -B and -C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. The genes encoding the Aurora kinases have been shown to induce cell malignant transformation, and their overexpression has been detected in several tumor derived cell lines and tissues, being often associated with a poor prognosis. Over the last decade, specific inhibitors of Aurora kinases exhibited in preclinical and early phase clinical studies a good therapeutic efficacy against several tumour types, including the highly aggressive anaplastic thyroid cancer and the medullary thyroid cancer. In the present review we'll first focus on the Aurora mitotic functions in normal cells; then we shall describe the main implications of their overexpression in the onset of genetic instability and consequent aneuploidy. We shall finally discuss on the effects of the functional inhibition of Aurora kinases on thyroid cancer cells growth and tumorigenicity.

Angiomegaly and arterial aneurysms.

Angiomegaly is characterized by an alteration in the elastic component of arterial and venous vessels determining their elongation and tortuousness. This involves an increased risk of thromboembolism and aneurysmal degeneration in affected subjects, even if they have been asymptomatic for a long time. The aim of this study is to demonstrate the correlation between angiomegaly and aneurysmal disease. A total of 163 patients suffering from a peripheral arterial aneurysm were included, 74 of these with an iliac aneurysm, 41 with a femoral aneurysm and 48 suffering from popliteal aneurysm. All patients were examined by color Doppler ultrasonography (CDU) and angio-CT with contrast medium. Eighteen cases of arteriomegaly were diagnosed, and the prevalence in the examined population was 11%. This study demonstrates the close association existing between aneurysms in peripheral arteries and arteriomegaly. Peripheral arterial aneurysms in association with arteriomegaly involve an increased risk of complications like thrombosis, embolism and rupture. The showed familiarity in the arteriomegaly incidence leads to predisposition of screening programs, using CDU, among relatives of patients affected by arteriomegaly and/or peripheral arterial aneurysms.

Is pattern III as evidenced by US color-Doppler useful in predicting thyroid nodule malignancy? Large-scale retrospective analysis.

OBJECTIVE: To evaluate whether pattern III of color Doppler Ultra-sound may identify malignant nodules. MATERIALS AND METHODS: We have retrospectively analyzed data pertaining to 1090 patients of both genders (230 males, 860 females), with an average age of 53 years (min 17 years, max 81 years), who underwent thyroidectomy in Department of Surgical Sciences of Sapienza University of Rome since January 2003 through June 2009. We correlated color-Doppler characteristics and histological features through statistical analysis so as to verify statistical correlation between them. RESULTS: Our study showed that 164/273 (60.1%) patients with malignant disease were associated with vascularization pattern III. Regarding benign disease, 152/268 (56.7%) patients showed a pattern of vascularization 3 at ultrasonography. The statistical analysis was not able to show any correlation between pattern III and malignancy. CONCLUSION: Pattern III cannot be used to predict malignancy with confidence, and FNA is still mandatory to rule out the nature of the nodule.