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Coronavirus disease (COVID-19) outbreak has profoundly changed the organization of hospital activities. We present our experience of reorganization of a nuclear medicine service settled in Northern Italy during the pandemic period of March and April 2020 characterized a government-mandated lockdown. Our service remained open during the whole period, performing approximately 80% of the routine practice, while maintaining it COVID-free despite the geographical context characterized by a high risk of infection. Reorganization involved all aspects of a nuclear medicine department, following local, national, and international guidelines for prioritizing patients, telephone and physical triages, deployment of appropriate personal protective equipment, social distancing, and logistic changes for scheduling examinations and disinfection procedures. All staff remained COVID-19-negative despite the unintentional admission of 4 patients who later turned out to be positive for the severe acute respiratory syndrome coronavirus 2. These adopted measures would serve as the basis for safe nuclear medicine services in the post-lockdown phase.

Background: The epidemiology of cardiovascular risk (CV) in the elderly is far from being defined, and the reasons why some subjects retain a healthy body while growing old while others are affected by different diseases or die prematurely are still unknown., Aims: To compare the CV risk pattern in two elderly cohorts living in North-East Italy., Materials and Methods: The Risk Of Vascular complications: Impact of Genetics in Old people (ROVIGO) study is a population-based study including 580 unrelated elderly subjects representative of general population living in Rovigo in the Veneto region. They were compared to a cohort of 580 age-gender-matched unrelated subjects from the CArdiovascular STudy in the Elderly (CASTEL) living in the same region in Castelfranco Veneto and Chioggia., Results: Blood pressure (BP), heart rate (HR), low-density-lipoprotein cholesterol, and prevalence of coronary heart disease, heart failure and chronic pulmonary disease were lower in the ROVIGO than in the CASTEL cohort, while high-density-lipoprotein cholesterol and the prevalence of diabetes were higher in the former than in the latter. In the ROVIGO cohort, diabetes, left ventricular hypertrophy, coronary and cerebrovascular diseases were more represented in men. In the CASTEL cohort, systolic BP was higher in women. In both cohorts, the lipid pattern was less favourable and HR higher in women, chronic pulmonary disease more represented in men., Conclusions: People living in Rovigo were at lower CV risk than those in Castelfranco Veneto and Chioggia, mainly due to lower BP values, better lipid pattern and lower prevalence of CV and pulmonary disease.

Background: BRAF(V600E) mutation, which represents the most frequent genetic mutation in papillary thyroid carcinoma (PTC), is widely considered to have an adverse outcome on PTC outcome, however its real predictive value is not still well stated. The aim of the present study was to evaluate if BRAF(V600E) mutation could be useful to identify within patients with intrathyroid ultrasound-N0 PTC those who require more aggressive treatment, by central neck node dissection (CLND) or subsequent postoperative (131)I treatment., Methods: Among the whole series of 931 consecutive PTC patients operated on at 2nd Clinical Surgery of University of Padova and at General Surgery Department of University of Trieste during a period from January 2007 to December 2012, we selected 226 patients with an intrathyroid tumor and no metastases (preoperative staging T1-T2, N0, M0). BRAF(V600E) mutation was evaluated by PCR-single-strand conformation polymorphism analysis and direct genomic sequencing. We analyzed the correlation between the presence/absence of the BRAF(V600E) mutation in the fine-needle aspiration (FNA) and the clinical-pathological features: age, gender, extension of surgery, node dissection, rate of cervical lymph node involvement, tumor size, TNM stage, variant of histotype, mono/plurifocality, association with lymphocitary chronic thyroiditis, radioactive iodine ablation doses, and outcome., Results: The BRAF(V600E) mutation was present in 104 of 226 PTC patients (47.8%). BRAF(V600E) mutation correlated with multifocality, more aggressive variants, infiltration of the tumoral capsule, and greater tumor's diameter. BRAF(V600E) mutation was the only poor prognostic factor in these patients., Discussion: In our series, BRAF(V600E) mutation demonstrated to be an adverse prognostic factor indicating aggressiveness of disease and it could be useful in the management of low-risk PTC patients, as supplementary prognostic factor to assess the preoperative risk stratification with the aim to avoid unnecessary central neck node dissection (BRAF pos.) or to perform complementary (131)I-therapy (BFAF neg.)., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Aim: To investigate the effects of changing surgical practices on thyroid cancer incidence in the Veneto Region (North-Eastern Italy)., Methods: Hospital discharge records of the period 2000-2010 were analyzed to detect trends in thyroid surgery rates by type of surgery and diagnosis. The association between surgery rates for benign and malignant diseases across the 21 Local Health Units (LHUs) was assessed by Poisson regression. In a second step, clinical and pathological charts of the year 2010 were retrieved from the larger regional surgical center. The proportions of total and incidental papillary thyroid micro carcinoma (PTMC) were compared with historical data. Factors influencing an incidental diagnosis of PTMC were analyzed by logistic regression., Results: Among 26,000 procedures performed in the Region, there was an increase with time in the proportion of total thyroidectomies (from 67% to 78%) and surgeries with a diagnosis of thyroid cancer (from 17% to 28%). Cancer surgery rates across LHUs resulted associated to surgery rates for benign diseases (P<0.001). In the largest regional center, the proportion of PTMC increased from 35% to 56%, of whom almost 60% were incidental cases. The probability of finding an incidental PTMC was higher in total thyroidectomies than in other procedures (odds ratio=1.84, 95% confidence interval 1.08-3.14)., Conclusion: Data from the Veneto Region suggest that the increase in PTMC is due to several factors: increased preoperative diagnosis, total gland removal, extensive histological examination. Moreover, geographical variations in cancer incidence were associated to surgery rates for benign diseases., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Recently, in Italy, the reimbursement for the use of rhTSH in preparing patients for radiometabolic treatment of iodine-avid metastases from differentiated thyroid cancer has been made possible. Intramuscular administration of rhTSH increases the radioiodine uptake and thyroglobulin production by thyroid cells. In addition to the previous indications on the use of rhTSH (mainly: serum thyreoglobulin assay with or without 131I scintigraphy and ablation with 131I of remnants in low risk patients), the reimbursement is now allowed for the treatment with radioiodine of iodine-avid loco-regional and distant metastases, in subjects with inability to reach adequate TSH levels and/or severe clinical conditions which could be potentially worsened by other concurrent diseases (history of stroke or transient ischemic attack, severe cardiac disease, renal failure or major psychiatric disorders). The Italian Medicines Agency (AIFA) approved this use (and added this hormone in the special list of drugs regulated by the D.Lgs 648/96) on the basis of a series of scientific evidences, proposed by a "team of experts". In the present paper we illustrate the scientific background of the use of rhTSH (clinical usefulness, economic considerations, aspects related to a better quality of life) that allowed the modification of the reimbursement and how it was made possible in the Italian legislative context.

Objective: To assess the addition value of ¹⁸F-Fluorodeoxyglucose (FDG) PET/computed tomography (FDG-PET/CT) vs. CT in detecting early metastatic deposits in bone marrow (BM)., Methods: From January 2009 to December 2010, 198 consecutive patients (88 male, 110 female; median age: 64 years) were retrospectively examined. All patients underwent ¹⁸F-FDG-PET/CT for disease evaluation: 65 for lung cancer, 66 for breast cancer, 57 for lymphoma and 10 for multiple myeloma. All scans were reviewed by a radiologist and a specialist in nuclear medicine for the identification of bone lesions. The presence of BM metastases was confirmed by biopsy, sequential PET/CT scan or magnetic resonance imaging when available. A patient-based analysis was performed., Results: Investigating the presence of skeletal metastasis, 94 (48%) patients had positive and 104 (52%) negative CT scan whereas 110 (56%) had positive and 88 (44%) negative FDG-PET/CT scan (P<0.001). The two imaging modalities were concordant in 178 (90%) patients for bone lesions; on the contrary 20 (10%) patients had discordant results (P<0.001). In 21 out of 178 concordant patients BM lesions were identified both in CT and FDG-PET, whereas nine out of the 20 discordant patients showed BM involvement at PET/CT only. Overall, PET/CT was able to identify 30 (15%) patients with BM lesions. In these latter patients, the maximum standardized uptake value (SUVmax) for BM metastases was 7.9±4.5 (range: 3.1-19.0), resulting slightly higher in patients with negative than positive CT scan (8.3±5.1 vs. 7.8±4.3, respectively; P=0.79)., Conclusions: FDG-PET/CT resulted more accurate than CT in early detection of BM metastases. The FDG-PET/CT images improve the staging of about 15% of our study population. PET/CT detected BM lesions mainly on the basis of their increased metabolic activity rather than on anatomical alterations. Moreover, it provided an accurate identification of tumour viability that was useful for treatment planning and follow-up., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The established treatment for differentiated thyroid carcinoma (DTC) is founded on total thyroidectomy and subsequent administration of radioiodine (131I) to ablate the thyroid remnant and to treat the metastatic disease. In the case of metastatic or recurrent disease, further cycles of 131I therapy are often necessary. The condition for maximizing the effectiveness of the treatment is to have an adequate stimulation from TSH, which must be >25-30 mIU/L. This elevation is achieved either discontinuing the hormone suppression therapy for an appropriate period, or administering recombinant human TSH (rhTSH). The latter has shown good clinical efficacy in patients with residual thyroid gland and is nowadays commonly employed since it is easy to use and allows to avoid the side effects of hypothyroidism. It thus represents a good alternative to thyroid hormone withdrawal for the remnant ablation, while is still open the question if its efficacy on the management of metastatic disease is superimposable to thyroid hormone withdrawal. To this purpose, a Panel of expert reviewed the literature, assessing the advantages and disadvantages for the patient, as well as the impact in terms of cost and benefit to the National Health Service. The work of the Panel concluded with a proposal for the use of rhTSH in selected patients with metastatic DTC, in which is considered the efficacy and safety of the product and is examined its use in terms of costs; this proposal was accepted by the Italian Drug Agency resulting in an update of the indications for rhTSH.

Objectives: Breast cancer is the second cause of death in women in Europe and North America. The mortality of this disease can be reduced with effective therapy and regular follow up to detect early recurrence. Tumor markers are sensitive in detecting recurrent or residual disease but imaging is required to customize the therapeutic option. Rising tumor markers and negative conventional imaging (US, X-mammography, CT and MR) poses a management problem. Our aim is to assess the role of 18F-FDG-PET/CT in the management of post-therapy patients with rising markers but negative conventional imaging., Materials and Methods: In the period from January 2008 to September 2009, 89 female patients with breast cancer who developed post-therapy rising markers (serum Ca 15-3 levels=64.8±16.3 U/mL) but negative clinical examination and conventional imaging were investigated with 18F-FDG-PET/CT., Results: Tumor deposits were detected in 40/89 patients in chest wall, internal mammary nodes, lungs, liver and skeleton. The mean SUVmax value calculated in these lesions was 6.6±1.7 (range 3.1-12.8). In 23/40 patients solitary small lesion were amenable to radical therapy. In 7 out of these 23 patients a complete disease remission lasting more than 1 year was observed., Conclusions: 18F-FDG-PET/CT may have a potential role in asymptomatic patients with rising markers and negative conventional imaging. Our findings agree with other studies in promoting regular investigations such as tumor markers and 18F-FDG-PET/CT rather than awaiting the developments of physical symptoms as suggested by current guidelines since the timely detection of early recurrence may have a major impact on therapy and survival., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: Anaplastic thyroid cancer (ATC) is a rare aggressive tumor arising from the follicular cells of the thyroid gland (as does well differentiated thyroid cancer, WDTC), but ATC cells do not retain any of the biological features of the original follicular cells, such as uptake of iodine and synthesis of thyroglobulin. Prognosis is almost invariably fatal. In this article the Authors review the pathology, epidemiology, clinical presentation, diagnosis and treatment options of ATC. ATC incidence typically peaks at the 6-7th decade of life (mean age at diagnosis 55-65 years), women representing 55-77% of all patients. ATC represents 2-5% of all thyroid tumors, with a decreasing trend with respect to the incidence of WDTC. The histologic patterns of ATC include giant-cell, spindle-cell and squamoid-cell tumors; these subtypes frequently coexist and are not predictive of patients' outcome. Immuno-cyto-chemistry for thyroglobulin is usually negative or weakly positive and some cases are also negative for keratin, particularly in the spindle-cell areas. ATC may arise de novo, but in most cases it develops from a pre-existing WDTC, especially the follicular subtype. Most ATC patients complain of local compressive symptoms, such as dysphagia, dysphonia, stridor and dyspnea in addition to neck pain and tenderness; in over 70% of the patients the tumor infiltrates surrounding tissues, such as fat, trachea, muscle, esophagus, and larynx. The clinical course of a rapidly enlarging mass that is firm and fixed to surrounding structures in an elderly patient is quite suggestive for ATC. Diagnosis can be confirmed by fine needle aspiration cytology or, in doubtful cases, by histology on core biopsy. Computed tomography (CT) scan and magnetic resonance imaging (MRI) are useful for defining the local extent of disease and for identifying distant metastases, as is also positron-emission tomography (PET) with [(18)F]FDG. Tracheoscopy and esophagoscopy should be performed every two months, or whenever patients refer the appearance or worsening of local symptoms. Bone scintigraphy may be included in the follow-up of patients with a longer survival and relatively good health. Because of its aggressive behavior, the latest American Joint Committee on Cancer Staging Manual classifies all ATCs as T4 and Stage IV tumors, regardless of their actual overall tumor burden. Treatment of ATC has not been standardized because it is not clear whether or not therapy is effective in prolonging survival; most patients die within six momths from diagnosis, primarily because of asphyxiation caused by local tumor invasion. When employed alone, surgery, radiotherapy, or chemotherapy are seldom adequate to achieve overall control of the disease, but a combination of these treatments may improve local control. Surgical treatment of local disease offers the best opportunity for prolonged survival if the tumor is intrathyroidal. When the tumor is extrathyroidal, the surgical approach to ATC is controversial. Some favourable results have recently been reported with newly developed chemotherapy agents and hyper-fractioned radiation therapy. Tracheostomy should be performed in patients with impending airway obstruction when death is not imminent from other sites of disease, and if patients are not candidates for local resection or chemoradiation. Interventional bronchoscopy, including Nd-YAG laser and airways stenting are alternatives to surgery in inoperable ATC-induced tracheal obstruction. Gene therapy is under investigation. Although very rare, ATC is a highly aggressive tumor that belongs to the group of killer tumors with median survival time not longer than 6-8 months. Surgery, chemotherapy and radiotherapy are the conventional therapeutic strategies performed in the attempt to improve survival. Unfortunately, very often they do not succeed any clinical benefit but only palliative, Results: New therapeutic strategies based on molecular approaches are desirable.

In the present prospective study started in 2004, we evaluated the potential role of the ''job on site'' model as a formative tool previously proposed by the ''Ministero della Salute'' in Italy and at the moment it is yet in an experimental phase in our Country. We applied this ''job on site'' model for the development of a new Nuclear Medicine Service in Rovigo Hospital (ULSS 18 of Veneto Region Italy). Moreover, there were planned, experimented and applied different organizing working models involving both physicians, technicians and nurses. The indicators of productivity realised in the period August 2004 to June 2007 were taken as end points. In our experience, the ''job on site'' model was particularly useful as a formative tool, and allowed a qualified preparation of the Service personnel as well as a rapid achievement of standard Regional and National indicators of productivity. Moreover, from a cost-effectiveness point of view, the daily working model we applied, that is based on a prolongation of the daily work per operator, proved to be highly effective in our Hospital. The data reported here may be of interest for the future planning of similar Services in the Public National and Regional Healthcare.

Aim: Debate exists in the literature about the optimal treatment to be adopted in patients with locally advanced differentiated thyroid carcinoma. We aimed to better define the most appropriate diagnostic and therapeutic protocol for this type of tumour., Methods: The clinical and histopathological records of 280 consecutive patients with locally advanced differentiated thyroid carcinoma, studied and operated on by the same surgical team in the period between 1967 and 2002, were reviewed., Results: With regard to overall survival, at univariate statistical analysis, the patient's age at diagnosis (threshold, 45 years), primary tumour size, local cancer extension at diagnosis (subtypes of T4), extent of thyroidectomy, performance of lymph node dissection and performance of post-surgical external radiotherapy were found to be significant prognostic variables. With regard to the appearance of recurrent disease during follow-up, at univariate statistical analysis, the patient's age at initial diagnosis (threshold, 45 years), primary tumour size, local cancer extension at diagnosis (subtypes of T4), extent of thyroidectomy, performance of lymph node dissection, presence of metastatic lymph nodes, performance of post-surgical 131I therapy and performance of post-surgical external radiotherapy were found to be significant prognostic variables. At multivariate statistical analysis, the patient's age at initial diagnosis, extent of tumour, extent of thyroidectomy and performance of lymph node dissection were the only independent prognostic variables., Conclusions: In our experience, an aggressive surgical approach at first diagnosis appears to offer a better prognosis in terms of both overall survival and disease-free time interval in patients with locally advanced differentiated thyroid carcinoma, especially those over 45 years of age.

Unlabelled: This study evaluated the accuracy of (99m)Tc-sestamibi scintigraphy and neck ultrasonography in patients with primary hyperparathyroidism (PHPT) and the role of intraoperative hand-held gamma-probes in minimally invasive radioguided surgery (MIRS) of patients with a high likelihood of a solitary parathyroid adenoma (PA). The study was undertaken under the aegis of the Italian Study Group on Radioguided Surgery and Immunoscintigraphy (GISCRIS)., Methods: Clinical records were reviewed for 384 consecutive PHPT patients undergoing radioguided surgery using a low dose of (99m)Tc-sestamibi. Selection of patients for MIRS instead of traditional bilateral neck exploration was based on preoperative imaging indicating a solitary PA. (99m)Tc-Sestamibi (37-110 MBq, or 1-3 mCi) was injected in the operating theater 10-30 min before the start of the intervention. Either 11-mm collimated (309 patients) or 14-mm collimated (75 patients) gamma-probes were used. Intraoperative quick parathyroid hormone (IQPTH) assay was used on 308 patients (80.2%)., Results: MIRS was successfully performed on 268 (96.8%) of 277 patients. Conversion to bilateral neck exploration was necessary in 9 patients (3.3%) because of either persistently high IQPTH levels after removal of the preoperatively visualized PA (4 patients), intraoperative frozen-section diagnosis of parathyroid carcinoma (2 patients), or hard-to-remove PA (3 patients). MIRS, which was performed under locoregional anesthesia in 72 patients, required a mean operating time of 37 min and a mean hospital stay of 1.2 d. MIRS was successfully performed also on 32 (78.0%) of 41 patients who had previously undergone thyroid or parathyroid surgery. No major surgical complications were observed in the MIRS group, and there were only 24 cases (11%) of transient postoperative hypocalcemia. The probe was of little help in patients with concomitant (99m)Tc-sestamibi-avid thyroid nodules and not helpful at all in patients with negative scan findings preoperatively. IQPTH measurement helped to disclose some cases of multigland parathyroid disease., Conclusion: (99m)Tc-Sestamibi scintigraphy, especially if combined with neck ultrasonography, is highly accurate in selecting PHPT candidates for MIRS. The low-dose (99m)Tc-sestamibi protocol (which entails a low-to-negligible radiation exposure to the surgical team) is safe and effective for MIRS. MIRS plays a limited role in patients with concomitant (99m)Tc-sestamibi-avid thyroid nodules and should be discouraged in patients with negative (99m)Tc-sestamibi finding preoperatively. IQPTH can be recommended during MIRS to facilitate intraoperative identification of previously undiagnosed multigland parathyroid disease.

The clinical and histopathological records of 149 consecutive patients with papillary thyroid microcarcinoma (PTMC), homogeneously studied and operated on by the same surgeon in the period 1990 to 2001, were reviewed. After a mean 6.5-year follow-up, three cases of loco-regional recurrence (2%) were observed. These three patients had all undergone partial thyroidectomy only and tumour relapse occurred in the residual thyroid tissue. No recurrence was observed in patients treated by total thyroidectomy and I. At variance with other reported series, no lymph node recurrence was observed in our series, in particular in the group of 23 patients with evidence of nodal metastases at initial diagnosis (three of whom were revealed by I scan after surgery). Therefore, a preventive effect of I treatment in our patient population can be hypothesized. However, prolonged follow-up will be necessary to clarify this. Due to the inability of current imaging modalities to select pre-operatively PTMC patients at risk for recurrence (presence of thyroid capsular invasion, multifocality and microscopic lymph node metastases), it appears reasonable to offer the patient total thyroidectomy when a pre-operative diagnosis of PTMC is reached. Moreover, the policy of our thyroid cancer centre is that, in these patients, post-surgical I scan should be obtained in order to detect unknown metastatic deposits, and I treatment should also be considered in patients with poor clinical and histopathological prognostic factors. In contrast, in patients operated on for benign thyroid disease and with delayed diagnosis of PTMC at definitive histopathological examination, re-operation might be avoided in the presence of unifocal disease without thyroid capsular invasion and with ultrasound-'normal' residual thyroid tissue. Close clinical and ultrasound follow-up is recommended, especially in patients who have undergone conservative surgery only.

Prognostic factors and therapeutic results in a group of 268 patients with differentiated thyroid cancer (DTC) aged over 60 years are reported. These cases were selected from a total of 1457 DTC-patients seen at our Center from 1967 to 1987. All elderly patients underwent total thyroidectomy, and were treated with 131I therapy and suppressive hormonal therapy. Moreover, external radiotherapy was performed in 20% and chemotherapy in 3.8% of all cases. Follow-up included periodical clinical examination, serum Thyroglobulin (Tg) determination, 131I total body scan (TBS), and echographic and radiologic survey. Several unfavorable prognostic factors were identified in elderly patients with DTC. In comparison with data obtained in a group of patients under 60 years of age, 1) the follicular histologic type was increased, papillary/follicular ratio was 1.1 vs 2.6; 2) the F/M ratio was decreased, 1.5 vs 2.8 for papillary tumors, and 1.7 vs 3.6 for follicular tumors; 3) the rate of cases with local extrathyroid tumor growth and distant metastases was higher, and 4) rates of metastases to bone and metastases with low 131I uptake were increased. Moreover, the 10-year survival rate in elderly patients with lymph node and distant metastases was significantly reduced compared to younger patients, both for papillary and follicular cancer. The finding of detectable serum Tg levels was well correlated with the presence of metastatic disease. Moreover, Tg sensitivity was higher than TBS in showing the presence of metastatic foci. DTC in elderly people must be considered an aggressive tumor both for follicular and papillary histologic types. A radical approach is recommended: total thyroidectomy, 131I administration, and suppressive hormonal therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated thyroid function of 108 home-reared Down syndrome (DS) patients. Five had overt hypothyroidism, 2 were hyperthyroid, and 33 had high TSH values with an exaggerated response to TRH test despite hormone levels in the normal range. This finding indicated subclinical hypothyroidism. Antithyroid antibodies (antimicrosome and antithyroglobulin) were present in 13 patients. At the same time we investigated 73 parents: only one mother was hypothyroid and antithyroid autoantibodies were found in only 8% of Down syndrome parents.