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We here analyzed the prevalence of extra-thyroidal malignancies (EM) in 6,386 female patients affected by different thyroid disease (TD). At first, an age-matched analysis of EM in all patients was performed. We then evaluated EM prevalence in four TD diagnostic categories: non-nodular TD (n = 2,159); solitary nodule (n = 905); multinodular TD (n = 2,871); differentiated thyroid cancers (n = 451). Finally, patients were grouped based on the absence (n = 3,820) or presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) (n = 2,369), or anti-Thyroid Stmulating Hormone (TSH) receptor autoantibodies (n = 197). A total of 673 EM were recorded. EM prevalence in TD patients was higher compared to the general population (Odds Ratio, OR 3.21) and the most frequent EM was breast cancer (OR 3.94), followed by colorectal (OR 2.18), melanoma (OR 6.71), hematological (OR 8.57), uterus (OR 2.52), kidney (OR 3.40) and ovary (OR 2.62) neoplasms. Age-matched analysis demonstrated that the risk of EM was maximal at age 0-44 yr (OR 11.28), remaining lower, but significantly higher that in the general population, in the 45-59 and 60-74 year age range. Breast and hematological malignancies showed an increased OR in all TD, while other cancers associated with specific TD. An increased OR for melanoma, breast and hematological malignancies was observed in both TPOAb and/or TgAb autoantibody negative and positive patients, while colorectal, uterus, kidney and ovary cancers showed an increased OR only in thyroid autoantibody negative patients. In conclusions, women affected by both benign and malignant TD, especially at a younger age and in absence of thyroid autoimmunity, have an increased risk of developing primary EM, thus requiring a careful follow-up and surveillance.

A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, but no information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, we evaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulated in the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed.A significant positive correlation between Aurora-A and Aurora-B mRNAs was observed (p=0.001). The expression of both Aurora genes was not affected by the BRAFV600E mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameters such as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well as disease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker in PTC patients.

Background: The rapid and dramatic incursion of the Internet and social networks in everyday life has revolutionised the methods of exchanging data. Web 2.0 represents the evolution of the Internet as we know it. Internet users are no longer passive receivers, and actively participate in the delivery of information. Medical education cannot evade this process. Increasingly, students are using tablets and smartphones to instantly retrieve medical information on the web or are exchanging materials on their Facebook pages. Medical educators cannot ignore this continuing revolution, and therefore the traditional academic schedules and didactic schemes should be questioned. Analysing opinions collected from medical students regarding old and new teaching methods and tools has become mandatory, with a view towards renovating the process of medical education., Methods: A cross-sectional online survey was created with Google® docs and administrated to all students of our medical school. Students were asked to express their opinion on their favourite teaching methods, learning tools, Internet websites and Internet delivery devices. Data analysis was performed using spss., Results: The online survey was completed by 368 students. Although textbooks remain a cornerstone for training, students also identified Internet websites, multimedia non-online material, such as the Encyclopaedia on CD-ROM, and other non-online computer resources as being useful., Discussion: The Internet represented an important aid to support students' learning needs, but textbooks are still their resource of choice. Among the websites noted, Google and Wikipedia significantly surpassed the peer-reviewed medical databases, and access to the Internet was primarily through personal computers in preference to other Internet access devices, such as mobile phones and tablet computers. Increasingly, students are using tablets and smartphones to instantly retrieve medical information., (© 2014 John Wiley & Sons Ltd.)

Results from national cancer registries reveal an association of thyroid cancers with extra-thyroidal malignancies. In this study, we evaluated the prevalence of breast cancer (BC) in women affected by both benign and malignant thyroid diseases (TD) in comparison to the general population. To this end, 3,921 female patients from central and southern regions of Italy were evaluated. Age-matched analysis of the prevalence of BC was carried out after dividing the patients into three diagnostic categories: (1) 1,149 patients with non-nodular TD; (2) 2350 patients with nodular TD; (3) 422 patients affected by differentiated thyroid cancers. Furthermore, the patients were grouped according to the absence (2,344 patients) or presence (1,453 patients) of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) or anti-TSH receptor auto-antibodies (124 patients). BC prevalence in TD patients as a whole was significantly higher compared to the general population, with an odds ratio (OR) of 3.33. Age-matched analysis showed that the risk of a BC in TD patients was higher in younger patients (age 0-44 years), with an OR of 15.24, which decreased with increasing age. Patients without thyroid auto-antibodies showed a higher OR for BC (p = 0.0005) than TD patients with TgAb and/or TPOAb. The results demonstrate that women affected by either benign or malignant thyroid disease have a significantly greater risk of BC, which is higher at a younger age. Furthermore, thyroid auto-antibodies appear to be protective against BC. These findings may contribute to the identification of common genetic and environmental factors underlying this disease association.

In bloodless surgery a series of measures has to be implemented to reduce the perioperative need for transfusion of whole blood or its components. Jehovah's Witness are the most representative group of patients opting for bloodless surgery as their faith follows strict believes that prohibits receiving blood. Geriatric patients requiring bloodless surgery are even more delicate and represent a challenge for surgeons. The physiological response of the over 65 year population to decreased hemoglobin level is slower and less effective than in young and adult patients. Herby we describe the perioperative protocol implemented in our surgical Department offered to geriatric Jehovah's Witness patients. Preoperative optimization of the patients is the key step in the preparation period. Intraoperative anesthetic and surgical measures are also required along with a strict postoperative follow-up. From our experience, bloodless surgery is feasible in the geriatric population as long as it is performed in specialized centers where a multidisciplinary team is prepared to specifically manage this scenario. Rigorous patients selection and preparation are mandatory., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Collar transverse incision is the typical surgical access for operations on thyroid and parathyroids. The cosmetic outcome resulting from its closure is of paramount importance given its anatomical exposure. The traditional methods of closure include metal clips, subcuticular stitch and glue. In this study we evaluated the cosmetic results on 10 patients who had their cervicotomy wound closed with clips comparing it to a second group of 10 patients who had the same incision closed with subcuticular stitch. The cosmetic outcome was evaluated with a questionnaire answered by the patients, by the operating surgeon and by a surgical nurse who was blinded to the technique used. The results of the questionnaire were grossly similar with no differences in the two groups. Only two complications were recorded in the subcuticular group. Both the techniques associate to similar cosmetic outcome, and the choice between the two should be left to the surgeon's personal preference., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Epithelial thyroid cancers are represented by the differentiated papillary and follicular thyroid carcinomas which, following dedifferentiation, are thought to give rise to the highly aggressive and incurable anaplastic thyroid carcinomas. Although derived from the same cell type, the different thyroid tumors show specific histological features, biological behavior and degree of differentiation as a consequence of different genetic alterations. Over the last few years, our knowledge regarding the molecular alterations underlying thyroid cell malignant transformation and cancer progression has considerably increased; however, the prognosis of differentiated thyroid cancer patients still relies on high-risk clinic-pathological variables. In particular, the actual staging systems provides only a rough prediction for cancer mortality and risk of recurrences, including in each risk group patients with highly different tumor-specific progression, disease-free interval and survival time. In order to improve DTC patient's risk stratification, both the European and the American Thyroid Associations proposed practical guidelines to integrate the actual staging systems with additional clinical features such as the tumor histological variant, the results of post-ablative whole body scan and the serum thyroglobulin levels. Despite that, patients within the same risk group still show a very heterogeneous behavior in terms of disease-free interval. As a consequence, the identification of new prognostic molecular biomarkers able to testify tumor aggressiveness is highly required. Here we'll review recently characterized new molecular markers potentially able to ameliorate the prognosis in DTC patients., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Measurement of thyroglobulin (Tg) protein in the washout of the needle used for fine needle aspiration biopsy cytology (FNAB-C) has been shown to increase the sensitivity of FNAB-C in identifying cervical lymph node (CLN) metastasis from well-differentiated thyroid cancer (TC). In this study, we evaluated whether routine measurement of Tg protein (FNAB-Tgp), Tg mRNA (FNAB-Tgm) and calcitonin (CT) mRNA (FNAB-CTm) in the FNAB washout of CLN increases the accuracy of FNAB-C in the diagnosis of suspicious metastatic CLN., Methods: In this prospective study 35 CLN from 28 patients were examined. Histology showed metastatic papillary TC (PTC) in 26 CLN, metastatic medullary TC (MTC) in 3 CLN, metastatic anaplastic TC (ATC) in 3 CLN and 3 metastatic CLN from extra-thyroidal cancers., Results: The overall accuracy of FNAB-C was 84.4%, reaching 95.7% when the analysis was restricted to PTC. Both FNAB-Tgp and FNAB-Tgm compared favorably with FNAB-C and shown diagnostic performances not statistically different from that of FNAB-C. However, FNAB-Tgp and FNAB-Tgm/FNAB-CTm were found useful in cases in which cytology results were inadequate or provided diagnosis inconsistent with patient's clinical parameters., Conclusions: We demonstrated that FNAB-C, Tg/CT mRNA and Tg protein determination in the fine-needle washout showed similar accuracy in the diagnosis of metastatic CLN from TC. The results of this study suggest that samples for Tg protein and Tg/CT mRNA measurements from CLN suspicious for metastatic TC should be collected, but their measurements should be restricted to cases in which FNAB-C provides uninformative or inconsistent diagnosis with respect to patient's clinical parameters.

Hypoxia-inducible factor-1α (HIF-1α) is frequently overexpressed and activated in many cancer types. However, its regulation and function in thyroid carcinomas are only partially known. Aim of our study was to demonstrate that adaptation to the hypoxic micro-environment by human papillary thyroid carcinoma (PTC) cells, in the absence of leukocyte infiltrate, induces a "molecular inflammation" process characterized by the expression of a large set of genes normally involved in inflammation. To address this, tumor, peritumor or normal host tissue from eleven human PTC surgical samples, were separated by laser capture microdissection (LCMD) and studied by real-time quantitative PCR and Western blot. In such condition, we observed an increased expression and activation of HIF-1α, NF-kB and pro-inflammatory genes only in tumor tissues. Importantly, an anti-inflammatory gene such as SOCS-1 was markedly down-regulated in tumor tissue compared to surrounding normal host tissue. Similar results were found in fine-needle aspiration biopsy (FNAB)-derived specimens from PTC and in hypoxic human papillary thyroid tumor cell line, BCPAP. Moreover, we also detected an elevated expression of metalloproteinase-9 (MMP9) both in solid tumor and in hypoxic-treated BCPAP cells. Our findings reveal that, in human PTC tumor, hypoxic conditions are accompanied by up-regulation of pro-inflammatory genes, down-regulation of anti-inflammatory genes and increased expression of MMP9. We propose that a better understanding of the pro- and anti-inflammatory pathways involved in the "molecular inflammation" process even in the absence of leukocyte, may help to clarify progression toward malignancy and may prove useful for new anti-tumor strategy., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Context: It has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAF(V600E) mutation have a worse prognosis. We showed in PTC that high levels of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) inversely correlate with disease-free interval (DFI)., Objectives: To investigate the effects of BRAF(V600E) on the expression of uPA and uPAR and to evaluate the prognostic relevance of BRAF(V600E) alone or in combination with uPA and uPAR. DESIGN/SETTING/PATIENTS/INTERVENTION: The case study included 91 patients with PTC. All patients underwent thyroidectomy and radioiodine therapy. Follow-up was available for 75 patients., Main Outcome Measures: The BRAF(V600E) mutation was analysed by sequencing and mutant allele-specific PCR amplification; uPA and uPAR expression by quantitative RT-PCR., Results: BRAF(V600E) was found in 44 of the 91 patients and associated with older age, but not with high-risk clinicopathological features. Urokinase PA and uPAR mRNA levels were higher in tumour tissues by 9·51 ± 1·30 and 4·64 ± 0·44 fold, respectively, compared to normal matched tissues, being significantly higher in BRAF(V600E) -positive patients. In vitro induction of BRAF(V600E) in PCCL3 cells caused a significant increase in both uPA and uPAR mRNAs. Higher levels of uPA and uPAR correlated with lymph node metastases, TNM stage and disease recurrences. Kaplan-Meier and multivariate analyses demonstrated that uPA and uPAR were associated with shorter DFI, while the BRAF(V600E) was not., Conclusion: In PTC, BRAF(V600E) induces uPA and uPAR expression. The latter, but not BRAF(V600E) , associates with advanced stages and shorter DFI. If confirmed in larger case studies, they may represent reliable prognostic markers for more accurate risk stratification and postoperative decision-making in patients with PTC., (© 2012 Blackwell Publishing Ltd.)

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the "Sapienza" University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient's thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule's malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients' presurgical selection.

Background: Tumor cells with stem-like phenotype and properties, known as cancer stem cells (CSC), have been identified in most solid tumors and are presumed to be responsible for driving tumor initiation, chemoresistance, relapse, or metastasis. A subpopulation of cells with increased stem-like potential has also been identified within sarcomas. These cells are endowed with increased tumorigenic potential, chemoresistance, expression of embryonic markers, and side population(SP) phenotype. Leiomyosarcomas (LMS) are soft tissue sarcomas presumably arising from undifferentiated cells of mesenchymal origin, the Mesenchymal Stem Cells (MSC). Frequent recurrence of LMS and chemoresistance of relapsed patients may likely result from the failure to target CSC. Therefore, therapeutic cues coming from the cancer stem cell (CSC) field may drastically improve patient outcome., Methodology/principal Findings: We expanded LMS stem-like cells from patient samples in vitro and examined the possibility to counteract LMS malignancy through a stem-like cell effective approach. LMS stem-like cells were in vitro expanded both as "tumor spheres" and as "monolayers" in Mesenchymal Stem Cell (MSC) conditions. LMS stem-like cells displayed MSC phenotype, higher SP fraction, and increased drug-extrusion, extended proliferation potential, self-renewal, and multiple differentiation ability. They were chemoresistant, highly tumorigenic, and faithfully reproduced the patient tumor in mice. Such cells displayed activation of EGFR/AKT/MAPK pathways, suggesting a possibility in overcoming their chemoresistance through EGFR blockade. IRESSA plus Vincristine treatment determined pathway inactivation, impairment of SP phenotype, high cytotoxicity in vitro and strong antitumor activity in stem-like cell-generated patient-like xenografts, targeting both stem-like and differentiated cells., Conclusions/significance: EGFR blockade combined with vincristine determines stem-like cell effective antitumor activity in vitro and in vivo against LMS, thus providing a potential therapy for LMS patients.

The expression pattern of estrogen receptor (ER) isoforms in normal and tumor thyroid tissues is still controversial and poor defined, therefore, a more detailed study of the distribution of these molecules is needed. Most discrepancies might be due to the methods utilized. We studied the expression of ER isoforms in human papillary thyroid carcinoma (PTC), in fine-needle aspiration biopsy-derived specimens, and in cells, using more accurate techniques, such as laser-capture microdissection, real-time quantitative PCR, and Western blot. Laser-capture microdissection allowed us to isolate homogeneous cell populations from human PTC surgical samples. Tumor, peritumor, or normal host tissue of the same sample were separately dissected and analyzed by RT-PCR and Western blot. Estrogen receptor-α mRNA was more expressed in cancer-microdissected cells from human PTC, as compared with microdissected cells obtained from surrounding normal host tissue (450 vs 12, P = 0.001). A similar pattern was observed with Western blot for the ER-a protein. By contrast, ER-β mRNA expression was not detected among the microdissected tissue fractions. Fine-needle aspiration biopsy-derived specimens showed a similar expression pattern to ER. Moreover, human PTC cell line BCPAP and cancer stem cells from PTC, analyzed under hypoxic conditions, showed a hypoxia-driven increase in ER-α expression. In conclusion, ER-α might have an important role in human PTC, and its overexpression can be studied in routine needle aspirate as a possible marker of malignancy.

Background: The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets., Methods: The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy., Results: The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar., Conclusions: We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment.

Context: The urokinase plasminogen activating system is implicated in neoplastic progression, and high tissue levels of urokinase plasminogen activating system components correlate with poor prognosis in various human cancers., Objective: The objective of the study was to investigate the prognostic relevance of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR), and the plasminogen activator inhibitor 1 (PAI-1) in human papillary thyroid cancer (PTC)., Design: The expression of uPA, uPAR, and PAI-1 genes was analyzed in PTC and normal matched tissues by quantitative RT-PCR. The case study consisted of 99 patients (21 males and 78 females) affected by PTC including 77 classical, 15 follicular, four tall cell, and three oncocytic variants. Forty-one patients had lymph node metastases at the time of diagnosis. All the patients underwent thyroidectomy and radioiodine therapy followed by thyroid hormone replacement therapy. Follow-up data were available for 76 patients up to 64 months., Results: The uPA, uPAR, and PAI-1 mRNA levels were significantly higher in PTC compared with normal matched tissues by 9.63 ± 1,29-, 4.82 ± 0.45-, and 5.64 ± 0.71-fold, respectively. The increased expression of uPA and uPAR correlated statistically with advanced pT and N status. The uPA was also significantly associated with advanced tumor node metastasis stages. The Kaplan-Meier analysis showed a significant association of uPA and uPAR levels with reduced patient disease-free interval (DFI), and this association was stronger in stage I patients., Conclusion: The study demonstrated that in PTC the increased gene expression of uPA and uPAR is associated with tumor invasiveness, advanced stages, and shorter DFI, suggesting their prognostic relevance. These observations warrant further investigation in larger patient populations with longer follow-up.

Background: The urokinase plasminogen activating system (uPAS) is implicated in neoplastic progression and high tissue levels of uPAS components correlate with a poor prognosis in different human cancers. Despite that, relative few studies are available on the expression and function of the uPAS components in human seminomas. In the present study we characterized the expression of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR) and the uPA inhibitors PAI-1 and PAI-2 in normal human testis and seminomas., Methods: The expression of the above genes was evaluated by means of quantitative RT-PCR, western blot, zymographic analysis and immunohistochemistry., Results: Quantitative RT-PCR analysis of 14 seminomas demonstrated that uPA and uPAR mRNAs were, with respect to control tissues, increased in tumor tissues by 3.80 +/- 0.74 (p < 0.01) and 6.25 +/- 1.18 (p < 0.01) fold, respectively. On the other hand, PAI-1 mRNA level was unchanged (1.02 +/- 0.24 fold), while that of PAI-2 was significantly reduced to 0.34 +/- 0.18 (p < 0.01) fold. Western blot experiments performed with protein extracts of three seminomas and normal tissues from the same patients showed that uPA protein levels were low or undetectable in normal tissues and induced in tumor tissues. On the same samples, zymographic analysis demonstrated increased uPA activity in tumor tissue extracts. Western blot experiments showed that also the uPAR protein was increased in tumor tissues by 1.83 +/- 0.15 fold (p < 0.01). The increased expression of uPA and uPAR was further confirmed by immunohistochemical staining performed in 10 seminomas and autologous uninvolved peritumoral tissues. Finally, variation in the mRNA level of PAI-1 significantly correlated with tumor size., Conclusions: We demonstrated the increased expression of uPA and uPAR in human seminomas with respect to normal testis tissues, which may be relevant in testicular cancer progression.

Background: Thyroid nodules that are read on cytology as follicular or Hürthle cell neoplasms (FN and HN, respectively) and indeterminate for malignancy require surgery to differentiate benign from malignant nodules. We analyzed FN and HN with indeterminate cytology to determine if there were differences in the rate and types of thyroid malignancy and if the rate of thyroid malignancy was influenced by age or sex., Methods: We analyzed 463 nodules with an indeterminate cytological diagnosis of FN and 140 nodules with an indeterminate cytological diagnosis of HN. The histopathological diagnosis after thyroidectomy was the method for establishing the diagnosis and type of malignancy., Results: For the entire series of 603 patients there were 106 (17.6%) with thyroid cancer; 80 of these had a cytology reading of FN and 26 had HN. Extrathyroidal invasion in the grouped HN and FN patients who had papillary thyroid carcinoma (PTC) was more common in females than in males (62% vs. 25 %, p < 0.05). The rate of thyroid cancer was similar in FN (17.3%) and HN (18.6%). The rate of Hürthle cell thyroid cancer was significantly higher in HN than in FN (5.0% vs. 0.7%, p < 0.01) and the rate of the oncocytic variant of PTC was also significantly greater in HN compared to FN nodules (23.1% vs. 1.7%, p < 0.05). The rate of follicular thyroid carcinoma was almost identical in patients with HN and FN (19.2% vs. 18.8 %)., Conclusions: There is little difference in the rate of malignancy between thyroid nodules with a cytological reading of FN indeterminate for malignancy and HN indeterminate for malignancy but there is a difference in the types of thyroid cancers in these groups. Hürthle cell thyroid cancer and the oncocytic variant of PTC is more common in nodules with an HN indeterminate for malignancy cytology reading than in nodules with a FN indeterminate for malignancy cytology reading. Since Hürthle cell thyroid cancer and the oncocytic variant of PTC are more aggressive than other thyroid cancers, it is likely that patients with an HN indeterminate for malignancy cytology will, as a group, have more aggressive thyroid cancers than those with an FN indeterminate for malignancy cytology.

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.

Although thyroglossal duct cysts represent a common developmental abnormality of the thyroid gland, malignant transformation is rare and occurs in only 1% of cases. This article describes four clinical cases observed at the Surgical Science Department of "La Sapienza" University of Rome between 1996 and 2000. Histologic examination indicated two pure papillary carcinomas, a sclerosing papillary carcinoma, and a follicular variant of papillary carcinoma. In all cases, treatment involved removal of the body of the hyoid bone and total thyroidectomy, which we associated with removal of the thyroglossal duct cyst. In one case, laterocervical lymphectomy was performed. Carcinoma multifocality was found in one patient. We recommend associating total thyroidectomy with removal of the tumor of the thyroglossal duct and of the body of the hyoid bone, because the carcinoma may be multifocal and there may be lymphatic invasion of the thyroid and to ensure a correct follow-up.

The diffuse sclerosing variant (DSV) of papillary thyroid carcinoma is known for its high aggressiveness, high incidence of lymph node metastases, and high incidence of pulmonary metastases, and thus its consequently poorer prognosis. In this study, we undertook a retrospective analysis of papillary thyroid carcinomas to assess whether DSV can be considered a predictive factor for prognosis. We performed a retrospective evaluation of the Department's database of patients with papillary thyroid carcinoma who had undergone total thyroidectomy from January 1992 to December 2000. Group I consisted of 83 DSV patients and Group II was 168 pure papillary carcinoma (PC) patients. A significant prevalence of multinodular thyroid disorder on diagnosis was found for PC (P < 0.05), whereas with DSV, there was a significantly higher prevalence of post-thyroiditis nodular thyroid disorder than with PC (P < 0.001). The incidence of laterocervical lymph node pathology on diagnosis was significantly higher for DSV (P < 0.05). In 3.6 per cent of PC patients and 15.7 per cent of DSV patients, we observed recurrences in the regional lymph nodes (P < 0.001). We found 1.2 per cent distant metastases in PC patients and 7.2 per cent in DSV patients (P < 0.05). One PC patient (0.6%) and three DSV patients (3.6%) died of tumor-related causes (P < 0.05). Our study demonstrated that diffuse sclerosing carcinoma leads to a poorer prognosis to the extent that its classification as an autonomous clinical pathological entity is justified. In conclusion, we can state that DSV is a form of papillary thyroid tumor characterized by its higher aggressiveness, diffuse intrathyroid growth, and high incidence of lymph node and pulmonary metastasis. Ultimately, this means a poorer prognosis. In the presence of risk factors indicating a possible increase in biological aggressiveness, adequate postoperative treatment and close follow-up become essential.

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.

Objective: To conduct a retrospective study of 39 patients with papillary carcinoma of the thyroid with histologic vascular invasion (VI+) and 361 patients without any sign of vascular invasion (VI-)., Summary Background Data: In the present study, we undertook a retrospective analysis of papillary carcinoma of the thyroid to assess whether histologically determined vascular invasion can be considered a predictive factor for prognosis., Methods: By means of a retrospective study, we evaluated the department's database of patients with papillary thyroid carcinoma who had undergone total thyroidectomy from January 1993 to December 1999., Results: Group I consisted of papillary carcinoma without any sign of vascular invasion (VI-) comprising 361 patients. Group II consisted of papillary carcinoma with vascular invasion (VI+) comprising 39 patients. At the time of diagnosis, we observed no metastases in patients with VI-, whereas a pulmonary metastasis was observed in 1 patient with VI+ (P = 0.0023). In 3.6% patients with VI- and in 20.5% patients with VI+, we observed recurrences in the regional lymph nodes (P < 0.001); we observed 6 (1.66%) distant metastases in patients with VI- and in the 12.8% patients with VI+ (P < 0.001). Three patients with VI+ (7.7%) and 2 patients with VI- (0.6%) died of tumor-related causes; these figures were found to be statistically significant (P < 0.001)., Conclusions: In papillary carcinoma, it should be noted that histologic vascular invasion may be considered as a sign of an increased tendency toward hematogenic invasion and consequent increase in the relative percentage of metastases; ultimately, this means a poorer prognosis. In the presence of risk factors indicating a possible increase in biologic aggressiveness, adequate postoperative treatment and close follow up become essential.

Ectopic lingual thyroid tissue is an uncommon congenital anomaly. Tumors with identical pathological characteristics to those arising in thyroid tissue may be present in ectopic locations, but there are very few cases of malignant ectopic thyroid tumors reported in the literature. We present a review of this phenomenon and report a case of papillary carcinoma of the base of the tongue, located in ectopic lingual thyroid tissue, in a 30-year-old woman. The patient's presenting symptoms were dysphagia and oral bleeding, and we performed radical resection of the neoformation at the base of the tongue with part of the muscles of the floor of the mouth and the body of the hyoid bone, as well as total thyroidectomy. Histological examination revealed a "sclerosing" papillary carcinoma. The patient was treated with 131I and substitutive thyroid hormonal therapy. An ultrasonogram done 5 years later showed bilateral laterocervical lymph node recurrence, which was effectively treated with bilateral laterocervical lymphectomy.

Background and Objectives: To determine whether thyroid carcinoma in elderly patients presents any peculiar characteristics, whether the greater biological aggressiveness of the neoplasm modifies the surgical treatment selected, and whether age greater than 70 years represents an independent prognostic factor., Methods: Retrospective analysis of case histories from the Department of Surgery of "La Sapienza" University of Rome; 403 patients subjected to total thyroidectomy between 1993 and 1999, with a minimum follow-up period of 3 years subdivided into three groups: group I (patients aged between 20 and 50 years), group II (patients aged between 51 and 70 years) and group III (patients aged >70 years). The surgical and postoperative treatment is uniform in all study groups., Results: Age greater than 70 years entails a significant increase in mortality; the mortality rate in the three groups was found to be 3%, 9% and 54%, respectively. Prognosis is significantly worse in the elderly patients group (group III) than in group I (P < or = 0.001) and in group II (P < or = 0.001); group II mortality was significantly higher than that of group I (P = 0.005); in group III, the neoplasm displays features of greater biological aggressiveness (greater incidence of undifferentiated forms, presence of lymph nodes at diagnosis and vascular invasion, locally advanced forms, greater incidence of stage IV)., Conclusions: Statistical analysis shows that the greater biological aggressiveness of the neoplasm in elderly patients worsens the prognosis, although an age exceeding 70 years itself represents an unfavourable prognostic factor; total thyroidectomy does not present any counter-indications in elderly patients.

The study aims were to characterize patients with insular thyroid cancer and to provide data on patient outcome after surgical therapy. We compared nine patients with insular thyroid cancer at the Department of Surgical Science of "La Sapienza" University of Rome with 27 patients of similar age and tumor size who had follicular and papillary cancer, for a minimum follow-up period of 24 months (range, 24-72 months). All of the patients examined underwent total thyroidectomy. Vascular invasion was observed in 44.4 per cent of insular carcinomas (P < 0.05 vs papillary carcinomas). No significant differences were observed regarding diagnostic method, multifocality, tumor nodes metastases (TNM), or stage. The death rate of patients with insular carcinoma (33.3%) was found to be higher than that of patients with follicular carcinoma (P < 0.05) and papillary carcinoma (P < 0.01). Relapsing lymph-node pathologies were observed in 4 patients (44.4%) with insular carcinoma (P < 0.05 vs those with follicular and papillary carcinomas). Distant metastases were observed in 66.6 per cent of insular carcinomas (P < 0.005 vs follicular carcinoma and P < 0.001 vs papillary carcinoma). At the end of follow-up, 2 patients (22.2%) with insular carcinoma were disease-free (P < 0.001 vs those with follicular and papillary carcinomas). Our study demonstrates an unfavorable prognostic role of the insular phenotype of thyroid cancer, such that this tumor can be classified as an autonomous clinical and pathological entity.

Haemangioendothelioma is a vascular tumour characterised by the proliferation of endothelial cells with an epithelioid appearance. The behaviour of this neoplasm is intermediate between haemangioma and angiosarcoma. It may be localised in a wide range of sites, with a preference for soft and bone tissue. It is only rarely localised in the head and neck and even more rarely in the salivary glands. We describe a case of haemangioendothelioma in a 28-year-old man that originated in the retroneural region of the parotid gland, compressing the gland tissue and posteriorly infiltrating the muscular plane. A total parotidectomy surgical operation including the removal of lymph nodes in the region was performed followed by radiotherapy. An immunohistochemical investigation, carried out using the oxidase-antiperoxidase method, indicated that the neoplastic elements of the marker of the endothelial cells CD34 were positive for vimentine and for muscle-specific actin, showing a moderate proliferative action of the cellular elements with MIB-1 positivity estimated at around 6%. The peculiarity of the case we describe resides in the rarity of the haemangioendothelioma localisation in the parotid gland.

We report a case of synchronous bilateral renal carcinoma treated by partial nephrectomy on the right and total nephrectomy on the left. Follow-up at 42 months after surgery showed no recurrence of the disease. The increasing use of diagnostic imaging techniques such as ultrasound tomography, computerised tomography and nuclear magnetic resonance now allows even small-sized renal formations to be identified. Synchronous bilateral renal tumour has a favourable prognosis, especially when compared with single or asynchronous renal tumours. The recommended intervention is total monolateral nephrectomy combined with partial nephrectomy. The treatment of neoplasms at a more advanced stage, of such a nature as to necessitate bilateral nephrectomy or chemotherapy, results in a significant increase in mortality. Recently, biological therapy has been proposed as a more promising short-term option using interferon-alpha (IFN-alpha) and gamma.

In this study the authors examine the experience of their department in treating parotid tumours, evaluating in particular the various surgical techniques as a function of the prognosis and the incidence of relapses. Between 1 January 1970 and 31 December 2002, 336 patients with parotid tumour were observed in the Department of Surgical Sciences of "La Sapienza" University in Rome. Two hundred and thirty-nine patients with benign tumours and 65 with malignant tumours were analysed. As far as histological forms were concerned, the benign forms presented a prevalence of pleomorphic adenomas (55.2%) and of Warthin's tumours (36.4%). In the case of malignant tumours, the highest incidence was found for mucoepidermoid carcinomas (29.3%). In the case of benign neoplasms, the surgical strategy opted for was preneural parotidectomy performed in 148 cases (61.9%). Relapsing pleomorphic adenomas were observed in 11.65% of patients controlled, and relapsing Warthin's tumours in 8.7%. In malignant tumours, total parotidectomy was performed in principle, with possible enlargement modulated as a function of tumour stage; owing to causes related to the neoplasm, 18 patients (38.3%) died. In the treatment of benign parotid tumours, preneural parotidectomy is the preferred surgical strategy as it significantly reduces the relapse rate and, when performed by skilled surgeons, is characterized by a complication rate comparable to that of conservative surgery. In the treatment of malignant tumours, total parotidectomy is the basic procedure; extension of the action and the use of ancillary techniques are dependent on tumour stage.

Total parathyroidectomy with autograft represents an optimal surgical technique in the treatment of secondary hyperparathyroidism. Relapsing hyperparathyroidism due to miliary-type nodular formations scattered over the autograft site represents a complication that is rarely described in the literature. We examined five case histories of patients relapsing as a result of miliary-type nodular formations in the autograft site; in four cases the relapse was localized in the upper limb and in one case in a pouch of the sternocleidomastoid muscle. The patients underwent removal of the hyperfunctioning parathyroid formations accompanied by demolition of the surrounding muscle tissue. The relapsing hyperparathyroidism caused by multiple miliary-type nodular formations is a rare occurrence, akin to parathyromatosis. The increasingly widespread use of total parathyroidectomy with autograft to treat secondary hyperparathyroidism can lead to an increase in the incidence of this complication. Correct surgical technique and a careful selection of the parathyroid tissue to be autografted can prevent this complication. Furthermore, extensive demolition of the muscle tissue in the autograft site can prevent further relapses. Intraoperative rapid parathormone assay was found to be predictive of the disease's persistence and recurrence.

Well-differentiated thyroid neoplasms may be included among the most frequently occurring thyroid carcinomas. Papillary ca. is without doubt the best behaved type. The aim of the present work is to perform a retrospective case history study to assess patients with con papillary ca. who have been treated surgically over the last 17 years and have been subjected to periodic checks. A sample of patients was therefore extrapolated who had all undergone total thyroidectomy for papillary ca. of the thyroid. The incidence of local recurrence of the disease was verified, together with the results at distance. Furthermore, the assessments performed were evaluated and compared. From the sample of patients observed we inferred that papillary carcinoma of the thyroid can have a good prognosis over time provided periodic random checks are carried out.

Objective: To evaluate the prognosis of papillary microcarcinoma (PMC) of the thyroid., Design: Prospective study., Setting: Teaching hospital, Italy., Subjects: 89 patients treated for papillary micro carcinoma of thyroid and followed up for at least 6 years (range 6-12)., Intervention: Total thyroidectomy and, for lymph node metastases, laterocervical lymphadenectomy., Main Outcome Measures: Sex distribution, mode of onset of disease, diameter of tumour, histological type, histological stage, presence of lymph node metastases at the time of operation and type of operation., Results: When the disease presented with laterocervical lymph nodes it was histologically more aggressive and included follicular (n = 3) and sclerosing (n = 4) types., Conclusion: Papillary microcarcinoma has an excellent prognosis if managed initially by total thyroidectomy.

The aim of the study was to investigate major vascular injury during laparoscopic cholecystectomy, which is a rare but potentially lethal complication if not recognized and treated swiftly, usually secondary to placement of the Veress needle or trocar. We report on our experience with a 35-year-old woman presenting an aortic laceration of the anterior wall and a puncture wound penetrating the anterior wall of the inferior vena cava. Repair of the injuries was done using a 5-0 Prolene suture mounted on pledgets. In addition, it was necessary to suture three mesenteric vascular injuries in the posterior peritoneum with Vicryl 2-0. The estimated blood loss was 1300 cc. The patient did well and was discharged on postoperative day 13. The distal abdominal aorta, inferior vena cava and large pelvic vessels are particularly prone to injury during laparoscopic cholecystectomy. In most cases, the vascular defect can be closed by direct suturing. Rarely is it necessary to reconstruct the injured vessel with an alloplastic prosthetic patch or a prosthetic implant.

We report a rare case of a peripheral primitive neuroectodermal tumor (PPNET) originating from the left ileopsoas muscle in an adult patient with neoplastic thrombosis of the left external iliac vein, the common femoral vein and the left popliteal vein. We performed a median laparotomy with an oblique left inguinal incision to remove the neoplasm, which consisted of a large mass surrounding the iliac-psoas muscles, extending from the transverse apophysis of the spinal column to Scarpa's triangle, and passing through the lacuna musculorum. Histopathological examination revealed a primitive neuroectodermal tumor (PNET) with focal areas of necrosis, hemorrhage and vascular invasion. Immunophenotyping was positive for CD99, NSE, and focally for CK. Ultrastructural examination of the neoplastic cells showed often multiple nuclei with dense chromatin and very large nucleoli. The patient was discharged ten days after the operation. Adjuvant treatment consisted of radiotherapy at a dose of 2000 cGy in five fractions followed by six cycles of chemotherapy. The venous thrombosis was treated by anticoagulant therapy and recanalization of the occluded veins was obtained after two months of therapy. An MRI scan, carried out 12 months later, showed a local relapse, which was treated with chemotherapy and arterial chemoembolization.

Carcinoma of the papilla is a rare cancer of the digestive tract; 5% of all gastrointestinal tract malignant neoplasms are periampullary. The authors report and discuss the case of one of their patients aged 79 years suffering from a tumour of the papilla. The case was characterized by the large size of the neoplasm (5.5 cm in diameter) and by the poor clinical conditions of the patient, who was suffering from Parkinson's disease and was at high operative risk. The surgical strategy chosen involved transduodenal excision of the tumour with duodenum-bile duct anastomosis and internal duodenum-Wirsung duct anastomosis. The authors first examine the hypothesis that carcinoma of the papilla may represent the evolution of an adenomatous lesion and then go on to assess the therapeutic strategy adopted in the treatment of these neoplasms: in patients at high operative risk a transduodenal excision of the tumour with duodenum-bile duct anastomosis and internal duodenum-Wirsung duct anastomosis may be a valid alternative to the conventional Whipple procedure.

The aim of this work was to analyze patients suffering from primary hyperparathyroidism (HPT) treated by traditional and miniaccess surgery, to demonstrate the validity and limits of intraoperative assay of PTH (iPTH). Between January 2000 and December 2001, at the Surgical Science Department of "La Sapienza" University of Rome, 29 patients affected by HPT, one of whom was a recidivist, underwent surgery for HPT and had a mean follow-up of 15 months (range, 6-24 months). The research showed that a decrease of >50% in iPTH values is indicative of resolution of clinical signs in 95% of cases. The use of iPTH in HPT for solitary adenoma in both classical and mini-invasive surgery yields a 100% success rate in terms of persistence, recidivism, and postoperative normocalcemia. iPTH is of assistance to the surgeon and allows treatment through mini-invasive access. In the case of solitary adenoma, iPTH is not only a biochemical histological examination but also a predictive test of normocalcemia.

This study analyses the diagnostic value of preoperative diagnostic imaging examinations in the identification and location of pathological parathyroid glands. We examined 77 patients with primary hyperparathyroidism using ultrasonography of the neck and Tc99m-MIBI scintigraphy for preoperative assessment purposes. All patients underwent surgical treatment. We compared the diagnostic imaging results with those furnished by histological examinations. TC99m-MIBI scintigraphy revealed the presence of a pathological parathyroid gland in 74/77 cases (96.1%) compared with 75/77 cases (97.4%) diagnosed by ultrasonography. The two examinations combined detected pathological glands in 100% of cases. The location of the pathological gland was correct in 57 cases (74.0%) at scintigraphy and in 56 cases (72.7%) at ultrasonography. In one case (1.3%) persistent hyperparathyroidism was demonstrated. There were no cases of relapse. In this study preoperative evaluation by ultrasonography and scintigraphy displayed great sensitivity in identifying and locating pathological parathyroid glands. Surgical neck exploration is still the gold standard in the correct location of pathological parathyroid glands measuring less than 5 mm.

Background/aims: C-kit expression is a sensitive marker for a specific group of mesenchymal tumors of the gastrointestinal tract, gastrointestinal stromal tumors, the histogenesis and prognosis of which are uncertain., Methodology: We have investigated the expression of c-kit by immunohistochemical analysis (APAAP method) in 12 out of 13 cases of mesenchymal gastrointestinal neoplasms operated from January 1991 to December 1998, in which the follow-up data were fully available. Furthermore, the c-kit expression was correlated both with the expression of vimentin, CD34 and the mitotic rate, and with the expression of muscle (muscle-specific actin-HHF35 and desmin) or neural (neuron-specific enolase) differentiation markers., Results: C-kit was expressed in all 12 cases (100%). Two different patterns of expression were observed: cytoplasmic in 7 (58.3%) cases and nuclear in 3 (25%) cases; in 2 (16.7%) cases both cytoplasmic and nuclear immunostaining was detected. Three (60%) out of the five cases showing a nuclear c-kit expression were also neuron-specific enolase positive, whereas none of the cases showing an exclusively cytoplasmic c-kit expression was neuron-specific enolase positive. The correlation between the two patterns of c-kit expression and the follow-up data have shown a trend towards a better prognosis in gastrointestinal stromal tumors with a nuclear c-kit immunostaining and neuron-specific enolase positivity, but the relatively low number of cases does not allow us to draw conclusions. In gastrointestinal stromal tumors the mitotic rate (> 2 x 10 HPF vs. < 2 x 10 HPF) is related with statistically significant differences (P < 0.05) to the 5-year survival (0% vs. 80%, respectively)., Conclusions: These findings, together with the already known c-kit nuclear immunostaining in normal adrenal medullary cells, suggest that a nuclear c-kit expression in gastrointestinal stromal tumors is consistent with a neural differentiation. In this study the mitotic rate has demonstrated a significant influence on the prognosis of gastrointestinal stromal tumors.