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Aims: Electrolyte imbalances are common in patients with heart failure. Several studies have shown that a low serum chloride level is associated with adverse outcomes in hospitalized patients with acute heart failure and in outpatients with chronic heart failure. We performed a systematic review and meta-analysis to assess the association of hypochloremia with all-cause mortality in patients with heart failure., Methods: Data search was conducted from inception through 1 February 2023, using the following MeSH terms: ('chloride' OR 'hypochloremia') AND 'heart failure'. Studies evaluating the association between serum chloride and all-cause mortality in patients with heart failure were included. The predefined primary outcome was all-cause mortality. Pooled hazard ratios and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model; fixed-effects model and leave-one-out sensitivity analyses were also performed., Results: A total of 15 studies, involving 25 848 patients, were included. The prevalence of hypochloremia ranged from 8.6 to 31.5%. Follow-up time ranged from 6 to 67 months. Hypochloremia as a categorical variable was associated with an increased risk of all-cause mortality [hazard ratio 1.56; 95% confidence interval (CI) 1.38-1.75; P  < 0.001]. As a continuous variable, serum chloride was associated with all-cause mortality (hazard ratio per mmol/l decrease in serum chloride: 1.06; 95% CI 1.05-1.07; P  < 0.001). Results were confirmed by using several sensitivity analyses., Conclusion: Hypochloremia exhibits a significant prognostic value in patients with heart failure. Serum chloride can be used as an effective tool for risk stratifying in patients with heart failure., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: patients with atrial fibrillation (AF) under treatment with chronic oral anticoagulation (OAC) often require coronary angiography with or without percutaneous coronary intervention (PCI). Deciding the management of OAC during this periprocedural period requires balancing the risks of hemorrhage and thrombotic complications. Guidelines recommend an uninterrupted strategy in patients receiving Vitamin-K Antagonists (VKA). However, for patients undergoing coronary angiography or PCI while on direct oral anticoagulants (DOACs), withdrawal 12-24 h prior to the procedure is still recommended. This is based on expert opinions given the lack of evidence. Therefore, whether DOAC discontinuation prior to trans-radial coronary procedures should be the strategy of choice is a matter of debate and solid evidence is needed to guide clinical decision making., Methods: The DOAC-NOSTOP study is a prospective, single-arm, open-label study evaluating the safety of DOACs continuation in 200 patients undergoing transradial percutaneous coronary procedures. DOAC treatment will not be interrupted throughout the periprocedural period. Primary outcome will be Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 events, assessed at a 30-day follow-up., Conclusions: The DOAC-NOSTOP is the first study prospectively assessing the risk of bleeding with uninterrupted DOAC in patients undergoing trans-radial percutaneous coronary procedures., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Community-acquired pneumonia (CAP) is a common lower respiratory tract infection, often complicated by cardiovascular events, including cardiac arrhythmias. New-onset atrial fibrillation (newAF) has been associated with increased mortality in CAP patients, especially in those critically ill; however, limited data on the prevalence of newAF in patients with CAP are available. We aim to estimate the pooled prevalence of newAF and its impact on adverse outcomes in patients with CAP, through a systematic review and meta-analysis. MEDLINE and EMBASE were systematically searched from inception to 27 January 2022. All studies reporting the prevalence of newAF in CAP patients were included and all-cause mortality was extracted when available. The pooled prevalence of newAF, 95% Confidence Intervals (CI), and 95% Prediction Intervals (PI) were computed. The inconsistency index (I 2 ) was calculated to measure heterogeneity. Subgroup analyses were also performed. A protocol for this study was registered on PROSPERO (CRD42022307422). Among 7,655 records retrieved, 10 studies were included, with a total of 280,589 CAP patients. Pooled prevalence of newAF in CAP patients was 7.6% (95% CI 6.4-9.0%, 95% PI 4.3-13.1%, I 2  = 95%). Subgroup analyses showed no significant differences according to geographical location or study design. Patients with newAF had a higher risk of mortality among the studies included in the systematic review. NewAF is a common complication, occurring in 7.6% of CAP patients, with prediction intervals suggesting an even higher burden. CAP patients who develop newAF during hospitalization may be at higher risk of mortality in both short- and long-term follow-up., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background and Objectives: Recurrent laryngeal nerve (RLN) paralysis is a fearful complication during thyroidectomy. Intraoperative neuromonitoring (IONM) and optical magnification (OM) facilitate RLN identification and dissection. The purpose of our study was to evaluate the influence of the two techniques on the incidence of RLN paralysis and determine correlations regarding common outcomes in thyroid surgery. Materials and Methods: Two equally sized groups of 50 patients who underwent total thyroidectomies were examined. In the first group (OM), only surgical binocular loupes (2.5×−4.5×) were used during surgery, while in the second group (IONM), the intermittent NIM was applied. Results: Both the operative time and the length of hospitalization were shorter in the OM group than in the IONM group (median 80 versus 100 min and median 2 versus 4 days, respectively) (p < 0.05). The male patients were found to have a five-fold higher risk of developing transient dysphonia than the females (adjusted OR 5.19, 95% IC 0.99−27.18, p = 0.05). The OM group reported a four-fold higher risk of developing transient hypocalcemia than the IONM group (OR 3.78, adjusted OR 4.11, p = 0.01). Despite two cases of temporary bilateral RLN paralysis in the IONM group versus none in the OM group, no statistically significant difference was found (p > 0.05). No permanent RLN paralysis or hypoparathyroidism have been reported. Conclusions: Despite some limitations, our study is the first to compare the use of IONM with OM alone in the prevention of RLN injuries. The risk of recurrent complications remains comparable and both techniques can be considered valid instruments, especially if applied simultaneously by surgeons.

Awareness of the influence of sex ands gender on the natural history of several diseases is increasing. Community-acquired pneumonia (CAP) is the most common acute respiratory disease, and it is associated with both morbidity and mortality across all age groups. Although a role for sex- and gender-based differences in the development and associated complications of CAP has been postulated, there is currently high uncertainty on the actual contribution of these factors in the epidemiology and clinical course of CAP. More evidence has been produced on the topic during the last decades, and sex- and gender-based differences have also been extensively studied in COVID-19 patients since the beginning of the SARS-CoV-2 pandemic. This review aims to provide an extensive outlook of the role of sex and gender in the epidemiology, pathogenesis, treatment, and outcomes of patients with CAP, and on the future research scenarios, with also a specific focus on COVID-19., (© 2022. The Author(s).)

The present review deals with the functional roles of iodine and its metabolism. The main biological function of iodine concerns its role in the biosynthesis of thyroid hormones (THs) by the thyroid gland. In addition, however, further biological roles of iodine have emerged. Precisely, due to its significant action as scavenger of reactive oxygen species (ROS), iodine is thought to represent one of the oldest antioxidants in living organisms. Moreover, iodine oxidation to hypoiodite (IO - ) has been shown to possess strong bactericidal as well as antiviral and antifungal activity. Finally, and importantly, iodine has been demonstrated to exert antineoplastic effects in human cancer cell lines. Thus, iodine, through the action of different tissue-specific peroxidases, may serve different evolutionarily conserved physiological functions that, beyond TH biosynthesis, encompass antioxidant activity and defense against pathogens and cancer progression.

The transcription factors involved in epithelial-mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients' clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

The American Joint Committee on Cancer has revised the Tumor-Node-Metastasis (TNM) staging system for papillary thyroid cancer (PTC) patients. We examined the impact of this new classification (TNM-8) on patient stratification and estimated the prognostic value of clinicopathological features for the disease-free interval (DFI) in a cohort of 1148 PTC patients. Kaplan-Meier analyses showed that all clinicopathological parameters analyzed, except age and multifocality, were associated significantly with DFI. Cox regression identified tall cell PTC variant and stage as independent risk factors for DFI. When the stage was replaced with age, tumor size, and lymph node (LN) metastases in the set of covariates, the lateral LN metastases stood out as the strongest independent predictor of DFI, followed by tall cell variant and age. A noteworthy result emerging from these analyzes is that regression models had lower Akaike and Bayesian information criterions if variables were categorized based on the TNM-7. In addition, we examined data from a different PTC patient cohort, acquired from The Cancer Genome Atlas database, to verify whether the DFI prediction could be enhanced by further clinicopathological and molecular parameters. However, none of these was found to be a significant predictor of DFI in the Cox model.

Background: We compared two systematic reviews, one focusing on transoral video-assisted thyroidectomy (TOVAT) and the other on minimally invasive video-assisted thyroidectomy (MIVAT), to highlight the pros and cons that can determine the choice of one or the other procedure., Materials and Methods: PubMed, Scopus and ISI Web of Science databases were searched for relevant articles published from 2000 to June 2018. Both searches were performed using the same keywords. All articles describing human surgical case series of any size were included, while the following were excluded: articles published in languages other than English, case reports, reviews, early cadaver and animal studies and old reports of cases now included in more recent works. Application of the above selection criteria yielded 151 articles on TOVAT and 246 on MIVAT. Of these, 34 articles were selected for inclusion in the present study: 17 for the TOVAT group and 17 for the MIVAT group. The comparison was made considering the most common variables used in evaluating thyroid surgery procedures. The statistical methods used were Cohen's delta, Student's t-test and the non-parametric Mann-Whitney U-test., Results: The variable 'operative time' was found to show a very large effect size, and 'hospital stay' also differed significantly between the MIVAT and TOVAT groups., Conclusions: TOVAT and MIVAT should not be considered in competition with each other, but seen simply as alternative choices. Both appear to be safe methods, comparable in terms of post-operative complications, although the main reason for using TOVAT seems to be purely aesthetic., Competing Interests: None

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

Introduction: The aim of this study is to perform a review of the English-language international literature concerning thyroid surgery performed through the transoral vestibular approach, to evaluate its flessibility and safety in terms of complications., Materials and Method: The review was carried out on 17 studies of 17 different Authors. The following variables were taken into consideration: first Author's name, nationality, year of publication, number of cases, hospital stay, conversion rate, type of surgical approach, total number of total thyroidectomies and loboisthmectomies, operative time range, intraoperative blood loss range, number and percentage of complications., Results: 736 procedures were performed: 289 total thyroidectomies and 447 loboisthmectomies. Surgical approach was trivestibular in 15 cases and combined (oro-vestibular) in 2 cases. The operative time varies from 43 minutes for a loboisthmectomy to 345 for a total thyroidectomy. Intraoperative blood loss ranges from 3 to 300 ml. Ten cases were converted into open surgery. The hospital stay varies from 1 to 10 days. Complications were: transient recurrent laryngeal nerve palsy in 34 cases, permanent in 2 cases; transient hypoparathyroidism in 62 cases. One case of postoperative bleeding, 22 postoperative seroma, 20 cases of mental nerve injury, 8 cases of operative wound infection., Conclusions: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a new surgical method, the use of which exclusively meets the aesthetic needs of some patients. Its specific complication is the injury of the mental nerves. Further studies, however, seem to be necessary, on numerically broader cases, to ascertain the real validity of the method.

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1 , PD-L2 , CD80 , and CD86 was evaluated at the mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the downregulation of CD80 was observed above all in ATC. In addition, the increased expression of CD80 associated with longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAF V600E mutation in PTC. The increased PD-L2 expression correlated with BRAF V600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 downregulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC.

Objective: To assess the effect of truncal ligation of the inferior thyroid artery in comparison with ligation of secondary branches as a risk factor for postoperative hypocalcemia., Data Sources: A search was conducted using the Medical Subject Headings and free-text terms "thyroid*" and "truncal ligation*" in PubMed Central, PubMed, Embase, and Latin American and Caribbean Health Sciences Literature databases for trials published between January 1985 and October 2016. A Google search with the same terms, and a "snowball" approach was designed to retrieve the largest number of articles., Review Methods: Controlled trials (randomized or not) of adults who underwent total/bilateral subtotal thyroidectomy were searched, and truncal ligation versus nontruncal ligation of the inferior thyroid artery was compared. Data were acquired following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological quality of randomized controlled trials was assessed in accordance with Cochrane Collaboration guidelines, and for nonrandomized controlled trials, the Newcastle-Ottawa quality assessment scale for cohort studies was used. Pooled results are presented as risk differences with a random effects model. The main outcome was postoperative temporary and definitive hypocalcemia., Results: We found 11 nonrandomized controlled trials and nine randomized controlled trials with 1940 patients: 977 patients in the trunk ligation group and 963 patients in the nontruncal ligation group. The risk difference for biochemical hypocalcemia was 6% (95% confidence interval [CI]: 2% to 11%), for symptomatic hypocalcemia 6% (95% CI: 1% to 10%), and definitive hypocalcemia 0% (95% CI: -1% to 1%) in the whole group., Conclusions: Truncal ligation of the inferior thyroid artery increases the risk of temporary and symptomatic hypocalcemia but not the risk of definitive hypocalcemia. Laryngoscope, 128:534-541, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5-1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves' disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s).

Thyroid nodules are very common, affecting 19%-67% of the adult population. However, about 10% of them harbor a malignant lesion. Consequently, the first aim in their clinical evaluation is to exclude malignancy. Fine-needle aspiration cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid nodules. However, FNAC has a main diagnostic limit, namely cellular atypias of indeterminate significance, which require surgical excision and histological examination to differentiate benign from malignant lesions. Histology reports show that approximately 80% of these patients harbor a benign lesion. Therefore, in order to reduce unnecessary thyroidectomy, over the last years, the cytological classification of thyroid nodules has been revised and a number of new instrumental and molecular approaches have been proposed. In the present article, we will attempt to summarize the most recent cytological, molecular and echographic strategies to enhance the diagnostic accuracy of preoperative thyroid follicular lesions. In particular, we will discuss the new cytological classifications from the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), the British Thyroid Association-Royal College of Pathologists (PTA-RCPath) and the new Italian Society for Anatomic Pathology and Cytology (SIAPEC 2014. We will review molecular tests evaluated to ameliorate follicular lesion diagnosis as well as the clinical utility of the new echographic Thyroid Imaging Reporting and Data System (TI-RADS) score., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Obesity is an independent cardiovascular risk factor and a catalyst of other cardiovascular risk factors, such as hypertension, dyslipidemia, type 2 diabetes mellitus (DM2) and metabolic syndrome., Methods: We analyzed cardiovascular risk in obese patients before and after sleeve gastrectomy (SG). To this end, we studied changes in body mass index (BMI), blood chemistry parameters that characterize the risk of atherosclerosis and instrumental parameters (objective markers of this risk), namely intima-media thickness (IMT) and flow-mediated dilation (FMD), the latter reflecting endothelial function. We also considered purely cardiac parameters-mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE)-which describe cardiac risk more specifically than the ejection fraction. Alteration of one or more of these parameters determines an increase in cardiovascular morbidity and mortality., Results: The results showed that weight loss, in patients undergoing SG, is accompanied by a reduced BMI and a marked improvement in blood chemistry, confirming what has already been shown in many other studies, but the most interesting finding was the effect of SG on the instrumental markers of atherosclerosis. In particular, carotid IMT was significantly reduced (p < 0.001) and FMD significantly improved. MAPSE and TAPSE also improved significantly at both follow-up assessments (p < 0.001)., Conclusions: This study suggests that SG should be considered from a broader perspective, i.e. as a weight loss treatment that also improves obesity-related morbidity and mortality, benefitting both the patient and, in an economic sense, the society as a whole.

Establishment and maintenance of the apical-basal cell polarity, required for proper replication, migration, specialized functions and tissue morphogenesis, relies on three evolutionary conserved complexes: PAR, CRUMBS and SCRIBBLE. Loss of cell polarity/cohesiveness (LOP/C) is implicated in cancer progression, and members of the polarity complex have been described as either oncogenes or oncosuppressors. However, no information on their role in thyroid cancer (TC) progression is available. In the present study, we evaluated the gene expression of the PAR complex members aPKCι, PARD3α/β and PARD6α/β/γ in 95 papillary TC (PTC), compared to their normal matched tissues and in 12 anaplastic TC (ATC). The mRNA and protein levels of investigated genes were altered in the majority of PTC and ATC tissues. In PTC, univariate analysis showed that reduced expression of aPKCι, PARD3β and PARD6γ mRNAs is associated with increased tumor size, and the reduced expression of PARD3β mRNA is associated also with recurrences. Multivariate analysis demonstrated that the presence of lymph node metastasis at diagnosis and the reduced expression of PARD3β are independent risk factors for recurrences, with hazard ratio, respectively, of 8.21 (p=0.006) and 3.04 (p=0.029). The latter result was confirmed by the Kaplan-Meier analysis, which evidenced the association between decreased PARD3β mRNA levels and shorter disease-free interval. In conclusion, we demonstrated that the expression of PAR complex components is deregulated in the majority of PTC and there is a general trend towards their reduction in ATC tissues. Moreover, a prognostic value for the PARD3β gene in PTCs is suggested.

Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) and VHL-172 (V2), were measured in a series of 96 PTC and corresponding normal matched tissues by means of quantitative RT-PCR. Variations in the mRNA levels were correlated with patients' clinicopathological parameters and disease-free interval (DFI). The analysis of VHL mRNA in tumor tissues, compared to normal matched tissues, revealed that its expression was either up- or down-regulated in the majority of PTC. In particular, V1 and V2 mRNA levels were altered, respectively, in 78 (81.3%) and 65 (67.7%) out of the 96 PTCs analyzed. A significant positive correlation between the two mRNA variants was observed (p < 0.001). Univariate analysis documented the lack of association between each variant and clinicopathological parameters such as age, tumor size, histology, TNM stage, lymph node metastases, and BRAF mutational status. However, a strong correlation was found between altered V1 or V2 mRNA levels and DFI. Multivariate regression analysis indicated higher V1 mRNA values, along with lymph node metastases at diagnosis, as independent prognostic factors predicting DFI. In conclusion, the data reported demonstrate that VHL gene expression is deregulated in the majority of PTC tissues. Of particular interest is the apparent protective role exerted by VHL transcripts against PTC recurrences., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Subclinical hypothyroidism (SCH) and chronic autoimmune thyroiditis (CAT) are linked to an increased risk of atherosclerosis and coronary heart disease (CHD). The aim of this study was to look for positive markers of CHD and correlations with thyroid blood tests in patients with SCH or CAT, but no symptoms of CHD, so as to identify CHD risk conditions that otherwise would likely be missed., Methods: We measured a series of thyroid, clinical-metabolic and cardiovascular parameters in 30 consecutive endocrinology patients enrolled in our ambulatory endocrinological referral center of "Sapienza" University of Rome. (19 with CAT, 11 with SCH) from January 2015 to March 2015. 13 asymptomatic subjects were enrolled as controls. In each patient, we measured a series of 34 thyroid, clinical-metabolic and cardiovascular parameters., Results: in the statistical analysis of collected data, the oblique principal components clustering procedure (OPC) revealed the presence of an interesting mixed cluster, composed of a thyroid parameter (TPO-Ab), a metabolic parameter (homocysteine level) and a cardiovascular parameter (MAPSE), in which we assessed the relationships between the single components. Our preliminary results indicate that in both groups of patients elevated TPO-Ab, when accompanied by reduced MAPSE and increased IMT and homocysteine values, may be taken to indicate the presence of clinically unrecognized CHD., Conclusions: Confirmation of these results in larger series of patients could justify hormone therapy for prevention of CHD in these thyroid patients versus placebo treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The most appropriate surgical management of "follicular neoplasm/suspicious for follicular neoplasm" lesions (FN), considering their low definitive malignancy rate and the limited predictive power of preoperative clinic-diagnostic factors, is still controversial. On behalf of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB), we collected and analyzed the experience of 26 endocrine centers by computerized questionnaire. 1379 patients, surgically treated after a FN diagnosis from January 2012 and December 2103, were evaluated. Histological features, surgical complications, and medium-term outcomes were reported. Total thyroidectomy (TT) was performed in 1055/1379 patients (76.5 %), while hemithyroidectomy (HT) was carried out in 324/1379 cases (23.5 %). Malignancy rate was higher in TT than in HT groups (36.4 vs. 26.2 %), whereas the rates of transient and definitive hypoparathyroidism following TT were higher than after HT. Consensual thyroiditis (16.8 vs. 9.9 %) and patient age (50.9 vs. 47.9 %) also differed between groups. A cytological FN diagnosis was associated to a not negligible malignancy rate (469/1379 patients; 34 %), that was higher in TT than in HT groups. However, a lower morbidity rate was observed in HT, which should be considered the standard of care in solitary lesions in absence of specific risk factors. Malignancy could not be preoperatively assessed and clinical decision-making is still controversial. Further efforts should be spent to more accurately preoperatively classify FN thyroid nodules.

Epithelial thyroid cancers (TC) comprise two differentiated histotypes (DTC), the papillary (PTC) and the follicular (FTC) thyroid carcinomas which, following dedifferentiation, are assumed to give rise to the poorly differentiated thyroid carcinomas and the rare, but highly aggressive and invariably fatal, anaplastic thyroid carcinomas. Although thyroid cancer mortality has not been changed, its annual incidence has increased over the last two decades, mainly because of the improved ability to diagnose malignant transformation in small non-palpable thyroid nodules. Despite DTC patients have a favorable prognosis, aggressive disease is more frequently observed in the elderly showing a higher disease-specific mortality. Of relevance is the high prevalence of nodular thyroid disease in aged patients being higher than 90%, in women older than 60 year, and 60% in men older than 80 year. This implies a careful evaluation of thyroid nodules in this group of patients in order to exclude malignancy. In fact, despite the tremendous progress in the comprehension of the underlying molecular mechanisms deregulated in DTC progression, several aspects of their clinical management remain to be solved and novel diagnostic strategies are sorely needed. Here, we will attempt to review new molecular approaches, which are currently being exploited in order to ameliorate the diagnosis of thyroid nodules.

The internal carotid artery agenesis is a rare malformation disorder. We report the case of a 12-year-old boy suffering migraine, who had presented an episode featuring amaurosis fugax, spontaneously regressed. CT angiography images show hypoplasia of the left common carotid artery with loss of opacification of the left internal carotid artery consistent to agenesis. Moreover CT scans through the skull base demonstrate absence of left petrous carotid canal and an hypertrophic left middle cerebral artery originating from an aberrant artery arising from the right cavernous carotid. All diagnostic examinations confirmed the presence of the internal carotid artery agenesis, as Lie's type IV. We started an annual follow up that over the next 7 years did not reveal any change in magnetic resonance angiography images.

The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy ( p = 0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly ( p = 0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk.

Aim: The continued hospitalization after total thyroidectomy is often due to the onset of hypocalcemic complications more than 24 hours after surgery. So it would be important to predict which patients will not develop the hypocalcemic complication to discharge them early. This was the aim of our study., Patients and Methods: Our retrospective study was conducted on 327 consecutive thyroidectomized patients, operated on for benign and malignant diseases. We evaluated the values of preoperative serum calcium levels (Cal0) and of the first postoperative day (Cal1) and two new variables were calculated (dCal and dCaln). The same thing was made on a subgroup of 111 patients in whom also parathiroyd hormone (PTH) values were detected. Statistical analysis was performed with the goal of determining if we could establish a safe criterion for discharge at 24 hours after surgery and if there is a correlation between suitability for discharge and diagnosis., Results: As to discharge, the predictive power of the discriminant function applied was significant both on the total of patients and in the subgroup of 111 patients, but it was clinically unacceptable because it would expose us to a 21% to 27% error rate. It is not possible to identify a threshold, below which to consider patients surely dischargeable. The diagnosis does not appear correlated with the suitability for discharge., Conclusion: On the basis of serum calcium and PTH levels in the first postoperative day, it is impossible to predict which patients can be discharged 24 hours after surgery without incurring in hypocalcemic complications.

Benign mammary lumps and mastalgia are the most common breast disorders; yet, there is no clear-cut consensus about the best strategy for their treatment. We hypothesized that a combination, including boswellic acid, betaine, and myoinositol, would be beneficial in breast disorders by exerting a pleiotropic effect on multiple pathways. Indeed, myoinositol has already been proven to modulate some factors involved in the genesis of breast diseases, such as fibrosis and metabolic and endocrine cues. In our study, 76 women were randomly assigned to either the experimental or the placebo arm. After six months of treatment, statistically significant differences between the two groups were recorded for pain relief (56% vs 17%) and breast density reduction (60% vs 9%). Furthermore, benign breast mass dimension showed a reduction in the experimental group (40% vs 16%). The combination of boswellic acid, betaine, and myoinositol has been demonstrated to be effective in the treatment of breast pain and radiologically and histologically confirmed benign breast mass and in the reduction of breast density, one of the pivotal risk factors for the development of breast cancer, without any side effects.

Background: We set out to study, through ultrasound examinations, the carotid bifurcation in men and women with/without carotid stenosis to look for anatomical and electrophysiologic differences. We evaluated other variables to look for differences that might explain the dissimilar behavior of this disease in the two sexes and the presence and impact of risk factors., Methods: We examined 974 subjects aged 25 to 88 years (478 men and 496 women) in whom we considered heart rate, smoking status, and the presence of hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia. Ultrasound examination of the neck vessels included measurement of intimal medial thickness (IMT), vessel diameter, and outflow area/inflow area ratio. We established plaque location, echogenicity and echostructure, and the percentage of stenosis owing to plaque and measured systolic velocity, flow direction, and the depth of detection of these parameters. We used the apnea and hyperpnea test to assess cerebrovascular reactivity., Results: Hypertension and hypercholesterolemia were the most frequent risk factors. Women had a higher heart rate, whereas men had significantly greater IMT. The presence of atheromatous plaque was significantly correlated with age in both sexes, with men having a higher prevalence of carotid plaques. The sexes differed significantly with regard to plaque location, echogenicity, echostructure, and intracranial circulation. Women had a slightly higher blood flow velocity in the intracranial arteries. Risk factors affected plaque formation and extent more in men than in women., Conclusions: These findings suggest that carotid stenosis is a gender-related trait.

Authors analyze their experience of parathyroid autotransplantation during total thyroidectomy, with the purpose of seeing whether this practice influenced the rate of postoperative hypocalcemia and/or hypoparathyroidism. We identified three groups of patients: group A, consisting of 57 patients, underwent parathyroid autotransplantation during total thyroidectomy; group B consisting of 87 patients not submitted to intraoperative autotransplantation in whom, as an incidental finding, a parathyroid gland was detected in the surgical specimen; group C consisted of 100 patients who did not undergo autotransplantation and whose surgical specimens were not found to contain parathyroid glands. The three groups were compared for sex and age as well as for a series of clinical and laboratory parameters on the first three postoperative days and at six months after surgery. The rate of permanent hypoparathyroidism was 3.5% in Group A, 3.45% in Group B, and 1% in Group C. Multivariate analysis revealed that all three groups showed postoperative recovery of calcium levels, although the rate and extent of this recovery differed between them. The control group showed a more rapid and more complete recovery of serum calcium values compared with Groups A and B. Calcium recovery in Groups A and B was comparable, in terms of both rate and extent. The same pattern of results emerged for the iPTH values. The analysis of the data showed that there were no significant differences in the analyzed parameters between Groups A and B. This suggests that parathyroid autotransplantation does not influence the rate of postoperative hypocalcemia and/or hypoparathyroidism., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine diseases worldwide. Surgery is the only potentially curable option for patients with this disorder, even though in asymptomatic patients 50 years of age or older without end organ complications, a conservative treatment may be a possible alternative. Bilateral neck exploration under general anaesthesia has been the standard for the definitive treatment. However, significant improvements in preoperative imaging, together with the implementation of rapid parathyroid hormone determination, have determined an increased implementation of focused, minimally invasive surgical approach. Surgeons prefer to have a localization study before an operation (both in the classical scenario and in the minimally invasive procedure). They are not satisfied by having been referred a patient with just a biochemical diagnosis of PHPT. Imaging studies must not be utilized to make the diagnosis of PHPT. They should be obtained to both assist in determining disease etiology and to guide operative procedures together with the nuclear medicine doctor and, most importantly, with the surgeon. On the contrary, apart from minimally invasive procedures in which localization procedures are an obligate choice, some surgeons believe that literature on parathyroidectomy over the past two decades reveals a bias towards localization. Therefore, surgical expertise is more important than the search for abnormal parathyroid glands., (© 2016 European Society of Endocrinology.)

The three members of the Aurora kinase family, Aurora-A, -B and -C, regulate several aspects of the mitotic process, and their aberrant expression and/or function causes mitotic abnormalities leading either to cell death or aneuploidy. They are found overexpressed in several human malignancies, including the papillary thyroid carcinoma (PTC). In the present study, we sought to establish whether Aurora kinase inhibition could be of any therapeutic value in the treatment of aggressive forms of PTC, enduring to radioactive iodide (RAI) ablation. To this end, the effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on 3 human PTC cell lines expressing either wild-type (K1 and TPC1) or mutant p53 (BCPAP). The two inhibitors were capable of reducing cell proliferation in a time- and dose-dependent manner, with IC₅₀ comprised between 65.4 and 114.9 nM for MLN8237, and between 26.6 and 484.6 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited Aurora-B phosphorylation of histone H3 on Ser10, however, it did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Time-lapse videomicroscopy evidenced that both inhibitors prevented the completion of cytokinesis, and cytofluorimetric analysis showed accumulation of cells in G2/M phase and/or polyploidy. Apoptosis was induced in all the cells by both inhibitors independently from the p53 status. In conclusion, in the present preclinical study MLN8237 and AZD1152 have emerged as promising drug candidates for RAI-insensitive PTC.

Small Ubiquitin–like MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.

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.

The present pilot study aims at analyzing the human activity of playing in the light of an indicator of human ecology (HE). We highlighted the four essential anthropological dimensions (FEAD), starting from the analysis of questionnaires administered to actual gamers. The coherence between theoretical construct and observational data is a remarkable proof-of-concept of the possibility of establishing an experimentally motivated link between a philosophical construct (coming from Huizinga's Homo ludens definition) and actual gamers' motivation pattern. The starting hypothesis is that the activity of playing becomes ecological (and thus not harmful) when it achieves the harmony between the FEAD, thus realizing HE; conversely, it becomes at risk of creating some form of addiction, when destroying FEAD balance. We analyzed the data by means of variable clustering (oblique principal components) so to experimentally verify the existence of the hypothesized dimensions. The subsequent projection of statistical units (gamers) on the orthogonal space spanned by principal components allowed us to generate a meaningful, albeit preliminary, clusterization of gamer profiles.

Background: Non-recurrent inferior laryngeal nerve (NRILN) is usually discovered during thyroid surgery. It is often associated with vascular abnormalities that can be detected with magnetic resonance imaging (MRI) or duplex ultrasound scan. The aim of this study was to compare the diagnostic sensitivity of ultrasonography with MRI to identify the vascular abnormalities associated to NRILN., Patients and Methods: We revised 2713 total thyroidectomies to select patients with NRILN. The NRILN was identified in 17 patients (0,6%). A postoperative ultrasonic duplex scanning and a MRI was performed in 15 cases as 2 patients refused to submit to the exams., Results: At MRI an unique origin of common carotid trunk and a concomitant aberrant retroesophageal subclavian right artery was showed in 11 patients. In 2 cases vascular abnormality consisted in separated origin of supra-aortic arteries. At duplex ultrasound scan only in 2 patients was impossible to identify vascular abnormalities detected at MRI. Tthe diagnostic sensitivity of duplex ultrasound was 84,6%., Conclusions: Preoperative duplex ultrasound is a non invasive method with high diagnostic sensitivity that can easily complete the preoperative thyroid ultrasonography.

Background: The authors have applied the selective embolization of thyroid arteries in the treatment of voluminous cervicomediastinal goiters, especially in patients at high surgical risk or reluctant to undergo surgical intervention and radioiodine therapy., Method: Selective arteriography was used to embolize the thyroid arteries in 2 patients with voluminous hyperfunctioning cervicomediastinal goiters and mediastinal compressive symptoms. The first patient had already undergone unsuccessful radioiodine metabolic therapy and had severe left ventricular insufficiency contraindicating surgery. The second patient, despite having no contraindications, declined surgery and radioiodine metabolic therapy., Results: Radiological embolization markedly reduced the goiters in volume, resolved the compressive symptoms, and also normalized thyroid hyperfunction. The second patient needed a second embolization procedure because the embolized arterial branches had partly recanalized., Conclusion: Selective embolization of thyroid arteries can be successfully used to treat selected patients as a preoperative procedure and as an alternative to thyroid resection. Embolization can be repeated to achieve the required therapeutic aims.

Background: The aim of the present study was to evaluate the efficacy of different strategies of intermittent pneumatic compression (IPC) for the treatment of lower limb claudication., Methods: Five study groups were prospectively studied. Group 1: 9 patients not undergoing IPC; Group 2; six patients undergoing IPC 1 hour/thrice-a-day/4 months; Group 3: six patients undergoing IPC 2 hours/once-a-day/4 months; Group 4; six patients undergoing IPC 1 hour/thrice-a-day/2 months; Group 5: six patients undergoing IPC 2 hours/once-a-day/2 months., Results: All patients completed the planned treatment schedule and stated a compliance of 33% in group 2, 83% in group 3, 66% in group 4 and 100% in group 5. Peak systolic velocity of the popliteal artery blood flow increased over baseline values particularly when IPC lasted 4 months (group 2: 85%, group 3: 81% vs. group 4: 76%, group 5: 73%). These beneficial effects lasted 10 months and vanished 14 months after the end of IPC treatment. The absolute claudication distance increased at the end of the treatment of 101% in group 2, 94% in group 3, 86% in group 4, and 83% in group 5, and it was still increased over the baseline values 14 months after the end of the treatment. No differences have been observed whether the treatment was performed once- or thrice-a-day., Conclusions: ICP treatment performed two hours once-a-day for four months provide excellent results with satisfactory treatment compliance. However, these effects are not durable and vanish about one year after the end of IPC treatment.

Castleman's disease (CD) is a rare lymphoproliferative disorder. Clinically CD has been subdivided in two forms: uni-centric and multicentric. The uni-centric type is limited to a single anatomic lymph-node-bearing region. The present report describes two cases of uni-centric CD: the first was an abdominal localization treated with a laparoscopic approach; the second was a submaxillary localization treated with a classical approach. In case 1 the laparoscopic approach permitted to reach diagnosis, not clear after diagnostic imaging procedures, and enabled a total and excellent resolution of the pathology because our patient, after eight months of follow up, has had no evidence of recurrence of the disease. In case 2 we want to highlight that CD should be considered in the differential diagnosis of a solitary neck mass and that the surgical treatment is diagnostic and curative at the same time.

We present the case of a 61-year-old male patient with chronic obstructive pulmonary disease and a large cervicomediastinal multinodular hyperfunctioning goiter that made thyroidectomy a daunting task, especially considering the risk of intraoperative bleeding. The preoperative computed tomographic (CT) scan showed the right thyroid lobe very deeply rooted in the mediastinum, below the horizontal plane passing through the aortic arch. The thyroid mass imprinted the arterious and venous innominate trunks. To avoid a median sternotomy and remove the enlarged thyroid through a cervical approach alone, we decided to reduce the goiter in volume preoperatively by embolizing the thyroid arteries. We embolized the superior and inferior left, and the inferior right thyroid arteries. We spared the superior right thyroid artery because its blood supply contributed little to thyroid perfusion. After embolization, the patient was treated with antithyroid agents and corticosteroid drug therapy. At the same time, severe leukocytosis developed, thyroid hormone values increased, and a CT scan obtained 7 days after embolization showed the thyroid unchanged in volume. We therefore discharged the patient and were waiting for his laboratory blood chemical findings to return to normal. Thirty days later the patient was readmitted to hospital, and a new CT scan showed that the thyroid mass had diminished to half its initial volume. We could therefore perform a total thyroidectomy through a cervical approach alone. The only problem arose in dissecting tight right inferior laryngeal nerve adhesions to the thyroid capsule, probably sequelae of postembolization thyroiditis. Even though preoperative thyroid-artery embolization cannot be considered a routine technique in cervicomediastinal goiter surgery, in a rare patient who presents with a voluminous goiter such as the one we describe here, it is a useful procedure.

Background: Extremely rare cases of paraneoplastic syndromes or ectopic production of proteins associated with liposarcoma are reported in literature. Production of Granulocyte-Colony Stimulating Factor, alpha-fetoprotein, paraneoplastic pemphigus and leucocytosis, Acrokeratosis paraneoplastica (Bazex's syndrome) are reported. The present report describes a case of retroperitoneal liposarcoma associated with small plaque parapsoriasis. Our search in the English literature of such a kind of association did not reveal any case reported., Case Presentation: A 74 year male patient was admitted to our hospital because of the presence of an abdominal mass in right iliac fossa. He also complained of a two-year history of psoriasiform eruptions. The CT scan showed a retroperitoneal pelvic mass. Therefore surgical resection of the tumor was performed. After surgery, the skin eruptions disappeared completely in seven days and so a diagnosis of parapsoriasis syndrome was done., Conclusion: Parallel disappearing of skin eruptions after surgery, typical clinical picture and not specific histology of the cutaneous lesions suggest the diagnosis of small plaque parapsoriasis. Therefore we propose to add Small Plaque Parapsoriasis to the list of paraneoplastic syndromes associated to liposarcoma.

Background: Tumor-induced hypophosphatemic osteomalacia is a syndrome characterized by urinary phosphate wasting related to the presence of a slowly-growing tumor of mesenchymal origin. The characteristic laboratory findings are normal serum calcium, marked hypophosphatemia, increased serum alkaline phosphatase, markedly reduced renal tubular reabsorption of phosphorus and inappropriately low levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D]., Case Presentation: A 65-year-old woman presented with a 17-year clinical history of musculoskeletal pain, muscular weakness in the pelvic girdle, spontaneous fractures and difficulty in walking. Over the ensuing years the patient suffered other multiple spontaneous fractures, surgically treated, and the muscular pains worsened until she became bedridden. During the years before hospital admission the patient received treatment with clodronate, oral calcium salts and vitamin D therapy. Standard laboratory, ultrasonography and scintigraphic findings provided a "convenient" diagnosis of primary hyperparathyroidism, but the low plasma level of phosphorus induced to perform an Indium111-octreotide scintigraphy. Scintigraphy visualized an area of pathologic increased signal uptake in the left groin, consistent with a mass containing a high density of somatostatin receptors. After surgery, histologic examination and immunostaining of the resected specimen indicated an hemangiopericytoma. Nevertheless, the persistently low blood phosphorus level, in association with the increased serum calcium and PTH levels, were attributed to the prolonged phosphate therapy the patient underwent over the years, and the persisting abnormal laboratory indexes indicated the development of a tertiary hyperparathyroidism. We performed a subtotal parathyroidectomy and intraoperative assay of serum PTH showed that levels had diminished by more than 80% from preoperative values. Over the ensuing months Ca+2, PTH and serum phosphorus values returned to normal, and the pain symptoms disappeared., Conclusions: Tumour-induced osteomalacia is a very rare syndrome associated in 5% of cases with tertiary hyperparathyroidism due to long-term therapy with phosphorus and vitamin D. The initial diagnosis of primary hyperparathyroidism, confirmed by the parathyroid MIBI-scintigraphy, would lead us to an inappropriate surgical treatment. Therefore we want to stress the importance of In111-octreotide scintigraphy in detecting tumours, rich in somatostatin receptors, in presence of an hypophosphatemic syndrome.

Background: Symptomatic hypocalcemia remains the main postoperative complication after total thyroidectomy. The aim of the present study was to evaluate the role of oral supplementation of calcitriol and calcium salts in preventing severe postoperative hypocalcemia after total thyroidectomy., Methods: A consecutive series of patients undergoing total thyroidectomy followed by administration of 500 mg of calcium salts 3 times per day were randomized to 3 different postoperative medical treatments: in group A, .5 microg of calcitriol twice per day was administered to 104 patients; in group B, 1 mmicrog of calcitriol twice per day was administered to 111 patients; and in group C, 202 patients did not receive calcitriol., Results: The rate of postoperative tetany in group A was 2.9%, in group B was 0%, and in group C was 7.4% (P=.03) and the rate of paresthesias was 28.8%, 17.1%, and 22.3%, respectively (P=.19). At discontinuation of calcitriol/calcium salts treatment, intact parathyroid hormone levels did not significantly differ from the preoperative levels. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve for serum concentration of calcium in predicting postoperative tetany was .749, .858 and .862 on the first, second, and third postoperative day, respectively. The best cut-off value of calcemia for prediction tetany was 7.5 mg/dL, and the rate of severe hypocalcemia on the third postoperative day was 23.1% in group A, 9.9% in group B, and 27.2% in group C (P=.001)., Conclusions: Oral administration of 1 microg of calcitriol twice per day and 500 mg of calcium salts 3 times per day after total thyroidectomy significantly decreases the risk of severe postoperative hypocalcemia.

The authors review 1,636 cases of total thyroidectomy with reference to specific complications, classifying them under the headings: major-minor, early-late, transitory-definitive. They report 19 cases of postsurgical haemorrhage, all within 12 hours of the operation, 31 transitory and 15 definitive cases of recurrent laryngeal nerve paralysis, and 14 cases of definitive hypoparathyroidism. As far as the minor complications were concerned, there was a greater incidence of seroma following the use of the harmonic scalpel. The risk factors and physiopathological mechanisms associated with each type of complication are analysed here, above all those responsible for the major and definitive complications. The need for routine preparation of the recurrent nerve, in order to prevent occurrence of postsurgical paralysis is stressed, as is the efficacy of vitamin D in preventing symptomatic postsurgical hypocalcaemia.

Background: Subjects with neurofibromatosis type 1 (NF1) show an increased risk of endocrine tumors, especially pheochromocytoma, whereas thyroid C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) are very rare events described only in adult patients., Method: A case of CCH diagnosed in a 14-year-old girl affected with NF1 is reported. Calcitonin serum level after pentagastin was elevated (286 pg/ml). Genetic testing was performed in order to rule out mutations in the RET proto-oncogene., Result: No germline mutation previously reported in MEN2 was detected. Multifocal and bilateral CCH was demonstrated by immunohistochemistry., Conclusion: It is suggested that in such a genetic background of high risk for malignancy, CCH could be considered as an extremely rare condition likely preceding MTC., (Copyright 2002 S. Karger AG, Basel)

Cellular fibronectins containing the extracellular domain A or B (EDA and EDB) are particularly abundant in fetal and neoplastic tissues. The presence of EDA and EDB was investigated in 28 cases of papillary carcinoma of the thyroid using IST-9 and BC-1 monoclonal antibodies. Immunostaining for EDA and EDB was detected in tumour stroma, in tumour basement membranes, and in tumour blood vessels. EDA was present in 27 of the 28 cases, in 20 of which more than 75 per cent of the tumour stroma was stained. Immunostaining for EDB was detected in 23 of the 28 cases and was less pronounced than that for EDA, being present in less than 25 per cent of the tumour stroma in most cases. Reactivity for EDA/EDB was not observed in the adjacent normal thyroid in any of the cases investigated. In a group of 20 non-papillary tumours, immunostaining for EDA was present in the stroma of three follicular carcinomas (one minimally and two widely invasive), one medullary carcinoma, and 5 of 16 follicular adenomas; expression of EDB was more restricted, being present in only the two cases of widely invasive follicular carcinoma. The presence of EDA and EDB was not correlated with the extent of fibrosis or the degree of tumour cell differentiation. Immunoreactivity was already present in microcarcinomas. These observations raise the possibility that the production of oncofetal fibronectins is an important step in papillary carcinoma tumourigenesis, perhaps facilitating adhesion and spreading of tumour cells., (Copyright 1999 John Wiley & Sons, Ltd.)

Background: The choice between subtotal and total thyroidectomy for multinodular goiter is controversial., Material and Methods: Subtotal and total thyroidectomy have been respectively performed in 108 and 451 euthyroid patients with multinodular goiter., Results: After subtotal and total thyroidectomy, transient recurrent laryngeal nerve (RLN) palsy occurred in 1 patient (0.9%) and 3 (0.6%), transient asymptomatic hypoparathyroidism in 27 (25%) and 131 (29%), and transient symptomatic hypoparathyroidism in 2 (1.8%) and 13 (2.9%), respectively (P = NS). After subtotal thyroidectomy, recurrence occurred in 27 patients (26%) Re-operation in 14 patients resulted in transient RLN palsy in 2 patients (14%), transient asymptomatic hypoparathyroidism in 6 (43 %) and transient symptomatic hypoparathyroidism in 2 (14%)., Conclusions: The failure to demonstrate any 'hormonal advantage' in preserving thyroid tissue by subtotal thyroidectomy, and the low morbidity rate and no need for re-operation after primary total thyroidectomy, make the latter the procedure of choice for the management of non-toxic multinodular goiter.

Of a total of 5,700 surgical procedures on the neck performed at our Institution between 1984 and 1995, 13 operations (0.22%) have been done on 11 patients with 16 cervical paragangliomas. A woman underwent resection of synchronous bilateral carotid body tumours and of an intravagal paraganglioma. Ten years later, after preoperative angiographic embolization, she underwent resection of a paraganglioma of the left hypoglossal nerve. Her sister, at age 21, underwent resection of a carotid body tumour and, respectively 19 and 20 years later, of a right and left intravagal paraganglioma. An interposition graft for replacement of the carotid bifurcation was necessary in one patient only. During resection of a left carotid body tumour, acute hypotension occurred resulting in an ischemic lesion of the right temporal lobe. Postoperatively, she also complained of respiratory distress that responded to medical therapy with difficulty. The related neurologic symptoms completely resolved three months after surgery. The operation for a paraganglioma of the left hypoglossal nerve resulted in a temporary motor deficit of the tongue and in permanent considerable difficulty in swallowing. Unilateral recurrent nerve palsy occurred in two patients. No patients during the postoperative follow-up showed signs of local recurrence or metastatic disease. In conclusion, surgery is an effective treatment for cervical paraganglioma, but because of the high surgical complication rate, an experienced and skilled surgeon is called on to optimize outcome. An adequate perioperative care is advisable.