5-year Follow-up of Reimplanted Parathyroid Glands in Forearm Subcutaneous Tissue During Thyroidectomy. A Confirmation of Graft Vitality in a Large Series of Patients.

INTRODUCTION: The aim of this study is to assess the outcomes of parathyroid gland reimplantation with PR-FaST technique in patients undergoing thyroid surgery, focusing on graft functionality over a 5-year follow-up period. MATERIALS AND METHODS: We analyzed data from 131 patients who underwent parathyroid reimplantation using the PR-FaST technique during thyroid surgery due to inadvertent parathyroid removal or evident vascular damage. Postoperative evaluations included serum calcium (Ca), magnesium (Mg), and phosphorus (P) analyses on the 1st and 2nd postoperative days, at 10 days, and at 1, 3, 6 months, 1 year, and 5 years of follow-up. Additionally, the mean values of serum intact parathyroid hormone (iPTH) concentration were measured from blood samples collected from both the reimplanted arm (iPTH RA) and non-reimplanted arm (iPTH NRA) within the same period. RESULTS: Among 131 patients, at 10 days post-surgery, only 46 patients (35.1%) out of 131 exhibited graft viability (iPTH ratio >1.5). This percentage increased to 72.8% (94 patients) after 1 month and further to 87.8% (108 patients) after 3 months post-surgery. At 1 year, 84.7% of patients showed good graft functionality. After 5 years, the percentage remained stable, with graft viability observed in 81.3% of patients. Only 91 of the initial 131 patients completed follow-up up to 5 years, with a dropout rate of 30.5 %. CONCLUSIONS: Parathyroid reimplantation using the PR-FaST technique is a viable option for patients undergoing thyroidectomy and has been shown to be a reproducible and effective technique in most patients, with sustained graft functionality and parathyroid hormone production over a 5-year follow-up period.

Early parathyroid hormone (PTH) level as a predictor of post-surgical hypoparathyroidism.

INTRODUCTION: Post-operative hypocalcemia and postoperative persistent hypoparathyroidism remain the most common complications after thyroidectomy. Many approaches have been developed to prevent them, but actually, a common protocol is not yet individuated. MATERIALS AND METHODS: We retrospectively analyzed the results of a prospectively collected database. We dosed PTH preoperatively and 4 h after surgery (PTH_4); calcium was evaluated preoperatively, on the first (I_POD) and on the second postoperative day (II_POD). Hypocalcemia was defined when calcium <8 mg/dl. PTH_4 and I_POD calcium serum levels are identified to predict postoperative hypocalcemia. RESULTS: Three hundred and forty-eight patients were enrolled, 37 patients resulted as hypocalcemic on I_POD and 41 on the II_POD. PTH_4 is related to I_POD (p < 0.001, r = 0.45) and II_POD (p < 0.001, r = 0.44) calcemia. PTH_4-cut-off predicting I_POD hypocalcemia was 10.50 pg/ml (sensitivity: 78.7%, specificity: 72.7%). A PTH_4 value of 11.5 pg/ml is able to predict hypocalcemia during II_POD (sensitivity: 76.5%, specificity: 69.2%). We set up a combined test to predict II_POD hypocalcemia, using PTH_4 and I_POD calcium (sensitivity: 77.8%, specificity: 89.9%). CONCLUSION: This research shows the association between PTH_4 and postoperative hypocalcemia. The PTH_4 cut-off to predict I_POD-hypocalcemia was 10.5 pg/ml. We analyzed the calcemia trend during the postoperative period and we realized a combined test using PTH_4 and I_POD-calcemia. This test improves the accuracy of the previous test. Further studies, in particular multicentric, with a larger sample are necessary to validate the combined model.

Definition of learning curve for thyroidectomy: systematic review on the different approaches.

Background: Thyroidectomy is one of the most common surgical procedures carried out worldwide and it has evolved in recent years with alternative approaches. With the advent of minimally invasive techniques, the learning curve (LC) concept has become a fundamental "dogma". Methods: A literature search, according to the PRISMA guidelines, was performed via PubMed (MEDLINE), Scopus, Cochrane Library, EMBASE, and Web of Science. Only studies assessing the learning process to thyroidectomy (including hemi- and total thyroidectomy), reporting a minimum of 30 procedures and describing clearly the minimum number of performances required to achieve proficiency and the main evaluation items used to establish it, were included. Conventional, endoscopic and robotic approaches were separately analyzed. Only English-language studies were considered. Results: Forty-five relevant studies were selected for the analysis [respectively 16 concerning robotic thyroidectomy (RT), 22 endoscopic thyroidectomy (ET), 6 mini-invasive video assisted thyroidectomy (MIVAT), 1 conventional thyroidectomy (CT)]. The number of procedures required for a single surgeon to achieve competence and the parameters used to define surgical proficiency were fully investigated for each individual technique. Conclusions: Our research shows how the current literature lacks an objective definition of the LC concept. The heterogeneity of analysis methodologies and parameters evaluated, the various surgical techniques and training background of single surgeons, make it impossible to draw univocal results. Future studies should consider confounding factors and establish criteria that should be consensually recognized in the assessment of surgical performances and skills.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Bilateral and Ipsilateral Central Neck Dissection in Total Thyroidectomy: a Long Term Comparison of Complications.

The role of prophylactic central compartment neck dissection (CCND) in total thyroidectomy (TT) is controversial in patients without clinically evident lymph nodes metastasis (cN0) because of association with transient and permanent hypoparathyroidism (HPT) as well as transient and permanent recurrent laryngeal nerve (RLN) injury. Instead of bilateral central neck dissection (bCCND), ipsilateral central compartment neck dissection (iCCND) has recently been proposed as a safer, alternative treatment for selected patients. The aim of this study is to characterize the morbidity that CCND (ipsilateral and bilateral) adds to TT. We enrolled 453 patients: Group A (316 patients) underwent TT alone, Group B (86 patients) underwent TT + iCCND, Group C (51 patients) underwent TT + bCCND. We compared the rates of RLN injury and HPT in three groups and data analysis showed that iCCND was associated with increased rate of transient HPT but not permanent HPT and bCCND was associated with increased rate of transient and permanent HPT, when compared with TT alone. Further studies are needed to evaluate the clear advantages of CCND (both ipsilateral and bilateral), but this should be considered in the context of an higher risk of surgical complications (especially transient and permanent hypoparathyroidism), in comparison with TT alone.

TIRADS, SRE and SWE in INDETERMINATE thyroid nodule characterization: Which has better diagnostic performance?

PURPOSE: To assess Strain Ratio (SRE) and Shear Wave Elastography (SWE) accuracy alone and with TIRADS classification, for the risk stratification of indeterminate thyroid nodules. MATERIALS AND METHODS: 128 Patients with 128 indeterminate nodules candidates for thyroidectomy underwent preoperative staging neck ultrasound and were classified according to K-TIRADS score. After TIRADS evaluation, semi-quantitative (SRE) and quantitative (SWE expressed in kPa) elastosonography were performed and relative diagnostic performances, alone and in combination, were compared through ROC curves analysis. In order to maximize the SRE and SWE sensitivity and specificity, their cut-off values were calculated using the Liu test. Bonferroni test was used to evaluate statistically significant differences with a p value < 0.05. RESULTS: Sensitivity, specificity, PPV and NPV were, respectively, 71.4%, 82.4%, 62.5%, 87.5% for K-TIRADS baseline US, 85.7%, 94.1%, 85.7%, 94.1% for SRE and 57.1%, 79.4%, 53.3%, 81.8% for SWE (kPa expressed). SRE evaluation showed the best diagnostic accuracy compared to the SWE (kPa expressed) (p < 0.05) and to the K-TIRADS (p > 0.05). The association of SRE with conventional ultrasound with K-TIRADS score increased sensitivity (92.9% vs 71.4%) but decreased the specificity than conventional US alone (76.5% vs 82.4%). CONCLUSION: Strain Elastosonography can be associated with K-TIRADS US examination in the thyroid nodule characterization with indeterminate cytology; in fact, adding the SRE to K-TIRADS assessment significantly increases its sensitivity and negative predictive value. However, further multicenter studies on larger population are warranted.

The THYCOVIT (Thyroid Surgery during COVID-19 pandemic in Italy) study: results from a nationwide, multicentric, case-controlled study.

The outbreak of the COVID-19 pandemic has led to a disruption of surgical care. The aim of this multi-centric, retrospective study was to evaluate the impact of the pandemic on surgical activity for thyroid disease among the Italian Units of Endocrine Surgery. Three phases of the pandemic were identified based on the epidemiological situation and the public measures adopted from the Italian Government (1st phase: from 9th March to 3rd May 2020; 2nd phase: from 4th May to 14th June; 3rd phase: from 15th June to 31st). The patients operated upon during these phases were compared to those who underwent surgery during the same period of the previous year. Overall, 3892 patients from 28 Italian endocrine surgical units were included in the study, 1478 (38%) operated upon during COVID-19 pandemic, and 2414 (62%) during the corresponding period of 2019. The decrease in the number of operations was by 64.8%, 44.7% and 5.1% during the three phases of COVID-19 pandemic, compared to 2019, respectively. During the first and the second phases, the surgical activity was dedicated mainly to oncological patients. No differences in post-operative complications were noted between the two periods. Oncological activity for thyroid cancer was adequately maintained during the COVID-19 pandemic.

Evidence on postoperative abdominal binding: A systematic review with meta-analysis of randomized controlled trials.

BACKGROUND: Midline laparotomy is an unavoidable approach to many surgical procedures. Many surgeons prescript the use of postoperative abdominal binder during the first mobilization after surgery. The use and the cost effective of this device is still debated by many surgeons. METHODS: PubMed, EMBASE and the CENTRAL were systematically searched for randomized controlled trials (RCT) comparing patients who wore abdominal binder ("binder") and patient who did not wear any abdominal binder ("non-binder") up to March 2020. The primary outcomes measured in the comparison were postoperative pain, pulmonary functions, the entity of physical activity, the comfort. A meta-analysis of relevant studies was performed using RevMan 5.3. RESULTS: wearing an abdominal binder after midline laparotomy seems to reduce postoperative pain on first and third postoperative day, to improve the physical activity on third postoperative day, and not affect pulmonary functions. Generally, an elastic abdominal binder is well tolerated during postoperative. CONCLUSIONS: the use of elastic abdominal binder permits a comfortable early postoperative mobilization reducing pain, increases physical activity and seems to not affect pulmonary functions.

Laparoscopic Mesogastrium Excision for Gastric Cancer: Only the Beginning.

Background: Surgery, with the aid of chemotherapy and radiotherapy, is the only curative chance for gastric cancer. Unfortunately, gastric cancer had an elevated recurrence rate, primarily locally. Mesogastrium excision (MGE) during D2 lymphadenectomy has the aim to remove all possible contaminated tissue around the stomach. Methods: PubMed, EMBASE, and the Web of Science (WOS) were systematically searched for MGE reports in gastric cancer up to March 2020. The outcome reported were the number of lymph nodes retrieved, operative time (OT), overall morbidity, intra- and postoperative complications, conversion rate, and length of hospital stay. Results: A total of six studies, including 518 patients, were considered eligible for this analysis. All the studies reported laparoscopic cases. The mean number of lymph nodes retrieved was 36.7 ± 10.1. Mean OT was 240.7 ± 10.1 minutes. One case of conversion is reported. Overall morbidity was 6%. Medium estimated blood loss was 50.2 ± 39.6 mL. Overall length of stay was 10.7 ± 0.7 days. Mean follow-up was 11 ± 1.4 months. Conclusions: Only few studies evaluated this item, and according to the available evidence, MGE is a feasible technique that could be performed, also laparoscopically, in all surgical resections for gastric cancer with curative intent. Further studies are essential to establish the clear indication of this invasive procedure.

Gonioprobe, an Innovative Gamma-probe to Guide Parathyroid Radioguided Surgery: First Clinical Experiences with Navigator and Lock-ontarget Functions.

BACKGROUND: Radioguided surgery represents a validated technique for the detection and the excision of abnormal parathyroid glands responsible for primary hyperparathyroidism (PHPT). To date little attention has been paid as to how the characteristics of gamma-probes can influence surgical procedure and time, thus having an impact on postoperative morbidity, hospitalization and costs. METHODS: We designed a new prototype of gamma-probe, the Gonioprobe, and tested its clinical utility in the operating room. Gonioprobe, thanks to its 5 scintillating independent crystals, performs the dual function of Navigator and Lock-on-target. These characteristics allow the immediate guidance of the surgeon's hand towards the source with very high precision, and with a much higher spatial resolution than commercial probes. Gonioprobe was used during intervention to detect abnormal parathyroid tissue, and to ensure no radioactivity in surgery bed after adenoma removal. RESULTS: We tested our gamma-probe on parathyroid adenomas particularly difficult to identify at a visual inspection due to anatomy modifications from previous neck surgery and/or characterized by uncommon localization. Moreover, parathyroid adenomas were hardly removable due to the proximity to the esophagus, neck vessels and/or recurrent laryngeal nerve (RLN). An intraoperative nerve monitoring system was used to protect the recurrent laryngeal nerve from injuries. Parathyroid hormone (PTH) assay and frozen biopsy confirmed the successful excision of the adenomas. CONCLUSION: The intraoperative use of the innovative Gonioprobe along with the nerve monitoring system allowed an accurate and safe removal of parathyroid adenomas and offered a significant advantage by reducing surgical time and postoperative complications, as well as hospitalization and costs.

Total Versus Completion Thyroidectomy: A Multidimensional Evaluation of Long-Term Vocal Alterations.

BACKGROUND: Total thyroidectomy (TT) and completion thyroidectomy (CT) are two common surgical operations that are frequently followed by vocal symptoms despite preservation of the recurrent laryngeal nerve (RLN) and of the external branch of superior laryngeal nerve (EBSLN). The aim of this study was to analyze vocal alterations through endoscopic findings, videolaryngostroboscopy (VLS), acoustic vocal parameters and impact on patients' quality of life after surgery in the absence of laryngeal nerve injury. METHODS: We enrolled 198 patients who underwent thyroidectomy by the same surgeon. One hundred twenty-six patients underwent TT (group TT) while 72 underwent CT (group CT). All patients underwent preoperative VLS and Voice Handicap Index (VHI) assessment and postoperative VHI, VLS and Acoustic Voice Analysis with Multidimensional Voice Program Analysis 12 to 18 months after surgery. RESULTS: We observed a statistically significant higher rate of EBSLN injury in CT compared to TT. Even in the absence of RLN and EBSLN injury, patients who underwent TT and CT presented slightly worse acoustic vocal parameters and VHI scores compared to healthy controls. Interestingly, some acoustic vocal parameters and VHI scores were significantly worse in group CT compared to group TT. CONCLUSIONS: The higher rate of EBSLN injury in CT rather than in TT suggests a higher surgical risk in CT. The vocal parameters of loudness and self-perception of voice were significantly worse after CT, suggesting a larger trauma in patients' vocal outcome in CT if compared to TT, although these alterations were not reported as psychologically limiting daily life of patients. Nevertheless, the existence of multiple factors contributing to vocal alterations after thyroidectomy highlight the importance of a routine comprehensive functional voice analysis before and after surgery.

Computer-aided diagnostic system for thyroid nodule sonographic evaluation outperforms the specificity of less experienced examiners.

PURPOSE: Computer-aided diagnosis (CAD) may improve interobserver agreement in the risk stratification of thyroid nodules. This study aims to evaluate the performance of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) classification as estimated by an expert radiologist, a senior resident, a medical student, and a CAD system, as well as the interobserver agreement among them. METHODS: Between July 2016 and 2018, 107 nodules (size 5-40 mm, 27 malignant) were classified according to the K-TIRADS by an expert radiologist and CAD software. A third-year resident and a medical student with basic imaging training, both blinded to previous findings, retrospectively estimated the K-TIRADS classification. The diagnostic performance was calculated, including sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristic curve. RESULTS: The CAD system and the expert achieved a sensitivity of 70.37% (95% CI 49.82-86.25%) and 81.48% (61.92-93.7%) and a specificity of 87.50% (78.21-93.84%) and 88.75% (79.72-94.72%), respectively. The specificity of the student was significantly lower (76.25% [65.42-85.05%], p = 0.02). CONCLUSION: In our opinion, the CAD evaluation of thyroid nodules stratification risk has a potential role in a didactic field and does not play a real and effective role in the clinical field, where not only images but also specialistic medical practice is fundamental to achieve a diagnosis based on family history, genetics, lab tests, and so on. The CAD system may be useful for less experienced operators as its specificity was significantly higher.

Parathyroid Autotransplantation During thyroid Surgery. Where we are? A Systematic Review on Indications and Results.

Introduction: Hypoparathyroidism still represents an important concern in thyroid surgery. Careful dissection with identification and preservation of parathyroid glands in situ remains the best way to maintain gland vitality and avoid post-operative failure. Nevertheless, parathyroid glands are still inadvertently removed in up to 11% of cases. Parathyroid autotransplantation may represent the only way to restore parathyroid gland functionality in case of inadvertent removal or devascularization during thyroid surgery. Despite this, there is still no agreement on the effectiveness of this procedure. The present systematic review is focused on the mainly debated matters regarding the procedure, indications, technique and results. Methods: This review has been carried out according to PRISMA statement and checklist. The research item was: (((parathyroid autotransplantation[Title]) OR parathyroid reimplantation[Title]) NOT hyperparathyroidism[Title]) AND english[Language]. Results: A total of 31 studies have been found according to limitations already described, reporting from 4 to 890 procedures, with a total amount of 4088 PA. Among these studies, there are only 7 prospective case-series evaluations, 2 prospective randomized trials, while the other 22 studies are retrospective evaluations. The main concerns are: when and how to perform autotransplantation; in which anatomical site; which result to be expected, and how to manage and control the graft. Conslusions: Parathyroid autotransplantatin is an important tool to avoid or minimize the risk for hypoparathyroidism following thyroid surgery in selected cases. Parathormone assay can help the surgeon to determine when reimplantation is indicated or not. Further studies could theoretically give definitive results.

Sonographic Presentation of Metastases to the Thyroid Gland: A Case Series.

Incidental sonographic discovery of thyroid nodules is an increasingly common event. The vast majority is benign, and those that are malignant, are generally associated with an indolent course and low mortality. Sonographic scoring systems have been developed to help clinicians identify nodules that warrant prompt fine-needle aspiration cytology (FNAC), but they are based largely on experience with papillary thyroid cancers. We analyzed the performance of four scoring systems widely used for this purpose (American Thyroid Association Guidelines, American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi Guidelines, European Thyroid Imaging Reporting and Data System, and Korean Thyroid Imaging Reporting and Data System) in patients whose nodules proved to be metastases from other solid cancers. Such nodules reportedly account for 0.2% to 3% of all thyroid malignancies. Each scoring system was used to assess retrospectively the malignancy risk and indications for FNAC of five patients' thyroid nodules that were ultimately diagnosed as metastases (from renal cell carcinoma, breast cancer, and lung cancer in two cases and esophageal cancer). The primaries identified in these cases are those most commonly reported to metastasize to the thyroid. In two cases, the thyroid metastases were the first sign of undetected neoplastic disease. Although sonography alone cannot distinguish thyroid metastases from primary thyroid malignancies, all four scoring systems classified the metastatic nodules as suspicious enough to require FNAC. The five cases accounted for 0.2% of those cytologically examined in our center. In most cases, cytology provided useful guidance for the subsequent management of these lesions, which differs from that of primary thyroid cancers and requires multidisciplinary input.

Spontaneous Deep Femoral Artery False Aneurysm Simulating a Neoplasm: A Rare Case and Literature Review.

A 70-year-old woman presented to our attention with a painless pulsating mass at the level of the upper left thigh without any previous history of trauma, arterial surgery, or puncture of the femoral artery. Duplex ultrasound showed a nodular angiomatous-like formation with deep venous compression; computed tomographic angiography and magnetic resonance imaging reported the presence of capsulated lesion vascularized by muscular branch of deep femoral artery (DFA). The patient underwent surgical excision of a very rare thrombized DFA branch false aneurysm. Spontaneous DFA false aneurysm, although rare, will be considered in absence of trauma or vascular catheterization or previous aneurysmal rupture.

Iodine deficiency in pregnancy: Still a health issue for the women of Cassino city, Italy.

OBJECTIVE: The World Health Organization, the United Nations Children's Fund, and the International Council for the Control of Iodine Deficiency Disorders recommend a median urinary iodine concentration (UIC) in pregnant women between 150 µg/L and 249 µg/L. In the present study, we evaluated whether in the urban area of Cassino (central Italy), after a national salt iodination program (30 mg/kg) was introduced in 2005, the increased demand of iodine during pregnancy was satisfied. METHODS: Between January 2016 and April 2017, 99 pregnant women were enrolled to evaluate UIC in spot urine samples, serum level of thyrotropin, free thyroxine, antithyroglobulin and antithyroperoxidase autoantibodies, and thyroid volume by ultrasonography. Eighty clinically healthy non-pregnant women were evaluated as controls. RESULTS: The median UIC was of 97.7 µg/L and 110.3 µg/L, respectively, in control and pregnant women. A significant increase (P < 0.001) of median thyroid volume was found in pregnant women, relative to control women, being, respectively, 10.4 mL (range 3.68-19.49 mL) and 7.16 mL (range 2.57-14.00 mL). A positive correlation was found between thyroid volume and anthropometric parameters, and an inverse correlation was identified between free thyroxine serum levels and anthropometric parameters. CONCLUSIONS: This observational study found that the majority of pregnant women and their fetuses appear not to be protected from the detrimental consequences of iodine deficiency. Therefore, the identification of new strategies to increase the knowledge and awareness of the general population regarding the beneficial effects of iodine supplementation during pregnancy is highly required.

Expression and prognostic value of the cell polarity PAR complex members in thyroid cancer.

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/ß and PARD6α/ß/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, PARD3ß and PARD6γ mRNAs is associated with increased tumor size, and the reduced expression of PARD3ß mRNA is associated also with recurrences. Multivariate analysis demonstrated that the presence of lymph node metastasis at diagnosis and the reduced expression of PARD3ß 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 PARD3ß 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 PARD3ß gene in PTCs is suggested.

Deregulated expression of VHL mRNA variants in papillary thyroid cancer.

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.

Consumption of iodized salt may not represent a reliable indicator of iodine adequacy: Evidence from a cross-sectional study on schoolchildren living in an urban area of central Italy.

OBJECTIVE: It has been established that iodine prophylaxis prevents endemic goiter. In this study we reported the amount of iodized salt sold by the retailers of Cassino, a city of central Italy. The aim of the study was to evaluate the effects of an iodine prophylaxis program started in 2005 on urinary iodine concentration (UIC) and thyroid volume (TV), and their correlation with anthropometric parameters in a population of schoolchildren. METHODS: The study included 234 schoolchildren (119 girls and 115 boys) ages 13 to 14 y. Each student provided a morning urine sample for UIC determination, and TV was evaluated by ultrasonography. Body weight and height also were measured. Each participant completed a questionnaire reporting the presence of thyroid disease and the consumption of iodized salt and iodine-rich food. RESULTS: The percentage of iodized salt sold by local markets was 42.4%. Median UIC in schoolchildren was 133.9 µg/L (range 33.2-819.5 µg/L), with 71 children having mild (range 50.1-99.9 µg/L) and 10 moderate (range 33.2-48.8 µg/L) iodine deficiency. Eleven children showed excessive iodine intake (range 300.4-819.5 µg/L). Median UIC was higher in children using iodized salt or consuming milk. Goiter prevalence was 3.8%. A positive correlation between TV and body weight, height, and surface was observed. CONCLUSIONS: The data reported may suggest the presence of an adequate iodine intake in the population of Cassino despite the low percentage of iodized salt sold by local retailers. This indicates that silent iodine prophylaxis through the consumption of iodine-rich or iodine-enriched food is of importance in the prevention of iodine deficiency disorders.

Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study.

BACKGROUND: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE: The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS: We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS: In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS: Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.