Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

Drawing as a Way of Knowing: How a Mapping Model Assists Preoperative Evaluation of Patients with Thyroid Carcinoma.

Background: Effective pre-surgical planning is crucial for achieving successful outcomes in endocrine surgery: it is essential to provide patients with a personalized plan to minimize operative and postoperative risks. Methods: Preoperative lymph node (LN) mapping is a structured high-resolution ultrasonography examination performed in the presence of two endocrinologists and the operating surgeon before intervention to produce a reliable "anatomical guide". Our aim was to propose a preoperative complete model that is non-invasive, avoids overdiagnosis of thyroid microcarcinomas, and reduces medical expenses. Results: The use of 'preoperative echography mapping' has been shown to be successful, particularly in patients with suspected or confirmed neoplastic malignancy. Regarding prognosis, positive outcomes have been observed both post-surgery and in terms of recurrence rates. We collected data on parameters such as biological sex, age, BMI, and results from cytologic tests performed with needle aspiration, and examined whether these parameters predict tumor malignancy or aggressiveness, calculated using a multivariate analysis (MVA). Conclusions: A standard multidisciplinary approach for evaluating neck lymph nodes pre-operation has proven to be an improved diagnostic and preoperative tool.

Management of surgical diseases of Primary Hyperparathyroidism: indications of the United Italian Society of Endocrine Surgery (SIUEC).

A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and health­care management protocol in parathyroid surgery published in 2014, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 12 members of the SIUEC highly trained and experienced in thyroid and parathyroid surgery. The main topics concern diagnostic test and localization studies, mode of admission and waiting time, therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications), hospital discharge and patient information, outpatient care and follow-up, outpatient initial management of patients with pHPT.

How to Manage Advanced Differentiated Thyroid Cancer: Step-by-Step Analysis from Two Italian Tertiary Referral Centers.

BACKGROUND: Differentiated thyroid carcinoma (DTC) has an excellent prognosis; however, advanced disease is associated with a worse prognosis and is relatively common. Surgery followed by RAI treatment remains the mainstream treatment for a large majority of patients with high- and intermediate-risk DTC, but its benefits should be carefully weighed against the potential for harm. The aim of this paper is to critically review the experience in treating advanced DTC at two tertiary referral centers in Italy. METHODS: Retrospective analysis of 300 patients who underwent surgery for ADTC over 30 years. RESULTS: The complication rate was 50.33%. A total of 135 patients (45%) remained at regular follow-up, 118 (87.4%) were alive, while 17 (12.6%) were deceased. The mean overall survival at 12 years was 84.8% with a mean of 238 months. Eleven patients (8.1%) experienced a relapse after a median of 13 months. CONCLUSIONS: ADTC patients adequately treated can achieve prolonged survival even in the case of metastasis or disease relapse. Patients with ADTC should be referred to high-volume centers with the availability of an extended multidisciplinary team to receive tailored treatment.

Parathyroid Retrospective Analysis of Neoplasms Incidence (pTRANI Study): An Italian Multicenter Study on Parathyroid Carcinoma and Atypical Parathyroid Tumour.

BACKGROUND: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). METHODS: All relevant information was collected about PC and APT patients treated between 2009 and 2021. RESULTS: Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%. CONCLUSIONS: Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter >3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis.

Ballistic Impacts with Bullet Splash-Load History Estimation for .308 Bullets vs. Hard Steel Targets.

The study focuses on testing a simplified way of estimating the resultant force due to ballistic impacts resulting in a full fragmentation of the impactor with no penetration of the target. The method is intended to be useful for the parsimonious structural assessment of military aircrafts with integrated ballistic protection systems by means of large scale explicit finite element simulations. The research investigates the effectiveness of the method in allowing the prediction of the fields of plastic deformation collected by hard steel plates impacted by a wide range of semi-jacketed, monolithic, and full metal jacket .308 Winchester rifle bullets. The outcomes show the effectiveness of the method being strictly related to the full compliance of the considered cases with the bullet-splash hypotheses. The study therefore suggests the application of the load history approach only after careful experimental investigations on the specific impactor-target interactions.

Italian Guidelines for the Management of Non-Functioning Benign and Locally Symptomatic Thyroid Nodules.

AIM: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. METHODS: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence and only those classified as "critical" were considered in the formulation of recommendations. RESULTS: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists. CONCLUSION: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated.

Crashworthiness of Additively Manufactured Auxetic Lattices: Repeated Impacts and Penetration Resistance.

Auxetic materials have recently attracted interest in the field of crashworthiness thanks to their peculiar negative Poisson ratio, leading to densification under compression and potentially being the basis of superior behavior upon impact with respect to conventional cellular cores or standard solutions. However, the empirical demonstration of the applicability of auxeticity under impact is limited for most known geometries. As such, the present work strives to advance the investigation of the impact behavior of auxetic meta-materials: first by selecting and testing representative specimens, then by proceeding with an experimental and numerical study of repeated impact behavior and penetration resistance, and finally by proposing a new design of a metallic auxetic absorber optimized for additive manufacturing and targeted at high-performance crash applications.

Metals release from stainless steel knives in simulated food contact.

The release of chromium, nickel, and manganese from knives stainless steel produced in Italy and People's Republic of China was investigated with the aim to check their quality and compliance with Italian Ministerial Decree 21.03.73, which is the most detailed text for the hygiene regulation of packaging, containers, and tools intended for food contact. Temperature effect on metal release is investigated in 18 sets of knives. Tests are performed by simulating discontinuous contact using a 3% glacial acetic acid solution in distilled water at 50°C and 100°C. Chromium, nickel, and manganese quantification is performed by total reflection X-Ray fluorescence. Chemical composition highlights low sulphur content, and most of them belong to the American Iron and Steel Institute (AISI) 420 type A stainless steel group. Tests performed at 100°C revealed higher concentration of released metals. Only three knives tested at 100°C exceed the limit of 100 µg L-1.

A Tale of Two Hypersecreting Adrenal Neoplasms in the Heartland of COVID-19 Pandemic, Lombardy, Italy.

In this study, we report the management, in Lombardy, Italy, of one patient with Cushing's syndrome due to adrenal adenoma and another one with pheochromocytoma, whose surgeries were deferred owing to the COVID-19 pandemic.

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.

False Positive of 68Ga-DOTATATE PET-CT in a Paraganglioma.

BACKGROUND: Functional imaging with 68Ga-DOTATATE PET-CT is widely employed to detect both primary and metastatic pheochromocytomas and paragangliomas (PGL), but its results may be occasionally misleading as in the case here reported. CASE PRESENTATION: We report here a 75-year-old woman with an interaortocaval PGL that was diagnosed after a hypertensive crisis occurring during the resection of a kidney tumor. 68Ga-DOTATATE PET-CT disclosed pathologic uptake in the abdomen and at the iliac crest. After the resection of the abdominal tumor, with the histological confirmation of PGL, arterial blood pressure and metanephrine levels were normalized. Genetic testing was negative. Thereafter, the bone lesion increased in size and became painful, requiring multiple medications. A selective biopsy disclosed a metastatic lesion arising from the renal tumor. CONCLUSION: The false-positive result of 68Ga-DOTATATE PET-CT is discussed.

Intraoperative parathyroid hormone testing in primary hyperparathyroidism surgery: time for giving up?

PURPOSE: Intraoperative PTH testing (IOPTH) in treatment of primary hyperparathyroidism (PH) is debated. Some authors advise against IOPTH in patients with concordant preoperative imaging undergoing focused parathyroidectomy. This study aims to compare focused parathyroidectomy success rates with and without IOPTH in patients with concordant preoperative imaging. METHODS: Retrospective cohort study involving 599 consecutive patients underwent surgery for PH from 2012 to 2017. Patients with discordant preoperative imaging were excluded. 426 patients underwent focused parathyroidectomy (214 patients without IOPTH and 212 with IOPTH) and were considered for the statistical analysis. In case of insufficient IOPTH decay (less than 50%), a bilateral exploration was carried out. RESULTS: The IOPTH group and the non-IOPTH group were similar for demographics and preoperative PTH and calcaemia. 413 patients were cured and disease persistence rates between groups were not significantly different (p > 0.05). CONCLUSIONS: Although further testing and randomized-controlled trials are required to validate our findings, our data show that IOPTH does not seem to improve the outcome in patients with concordant preoperative imaging undergoing focused parathyroidectomy.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

Intraoperative neuromonitoring in thyroid surgery: a point prevalence survey on utilization, management, and documentation in Italy.

The frequency of neuromonitoring during thyroid surgery is underreported in Italy. The present survey depicts and describes the patterns of use, management, documentation for IONM devices of IONM during thyroid surgery by surgeons in Italy. A point prevalence survey was undertaken. Source data were mixed from Italian surgeons attending the 2014 International Neuromonitoring Study Group (INMSG) meeting, four IONM manufacturers available in Italy and surgical units were identified from Company sales data. Qualitative and quantitative data were used to analyze. Questions probed IONM prevalence, surgeon background, hospital geographic practice locations, type of hospital, rationale for IONM use, sources of initial capital investment for IONM acquisition, type of equipment, use of continuous IONM, monitoring management, use of distinctive standards, and IONM documentation. IONM is currently delivered through 48 units in Italy. In 2013, the distribution of IONM by specialties included: general (50 %), ENT (46 %), and thoracic surgery (4 %). Overall, 12.853 IONM procedures were performed in the period from 2006 to 2013: 253 were performed in 2007 and about 5,100 in 2013. Distribution according to the type of hospital is: public 48 %, academic setting 37 %, and private maintenance 15 %. The use category of high volume thyroid hospitals represented 33 %. Initial capital investment for the acquisition of the monitoring equipment was 67 % public and 33 % with charitable/private funding. Audio plus graphic and EMG electrodes surface endotracheal tube-based monitoring systems accounted for the majority. Continuous IONM was introduced in 5 Academic Centers. Overall motivations expressed are legal (30 %), RLN confirmation (20 %), RLN identification (20 %), prognosis (10 %), helpful in difficult cases (10 %), decrease surgical time (5 %), and educational (5 %). The survey revealed that participants had few experience with the standardized approach of IONM technique (28 %). General IONM information to patients and/or subsequent specific IONM informed consent was initiated in 8 % of centers. EMG determinations were included in medical chart in 20 %. There were no significant associations found between all parameters considered. The present study describes an increased utilization of IONM in Italy. We highlighted areas for improvement in the management and documentation of IONM.

Electrodeposition of nanostructured bioactive hydroxyapatite-heparin composite coatings on titanium for dental implant applications.

In this paper we describe the one-pot fabrication of hydroxyapatite (HA)-heparin composites by electrodeposition onto Ti substrates and their characterisation in terms of structure, morphology, heparin content and bioactivity. HA coatings are well known and widely applied osteointegration enhancers, but post-implant healing rate in dental applications is still suboptimal: e.g. coagulation control plays a key role and the incorporation of an anticoagulant is considered a highly desirable option. In this study, we have developed an improved, simple and robust growth procedure for single-phase, pure HA-heparin films of thickness 1/3 µm. HA-heparin, forming nanowires, has the ideal morphology for bone mineralisation. Staining assays revealed homogeneous incorporation of sizable amounts of heparin in the composite films. The bioactivities of the HA and HA-heparin coatings on Ti were compared by HeLa cell proliferation/viability tests and found to be enhanced by the presence of the anticoagulant.

Open versus endoscopic adrenalectomy in the treatment of localized (stage I/II) adrenocortical carcinoma: results of a multiinstitutional Italian survey.

BACKGROUND: We compared the oncologic effectiveness of open adrenalectomy and endoscopic adrenalectomy in the treatment of patients with localized adrenocortical carcinoma. METHODS: One hundred fifty-six patients with localized adrenocortical carcinoma (stage I/II) who underwent R0 resection were included in an Italian multiinstitutional surgical survey. They were divided into 2 groups based on the operative approach (either conventional or endoscopic). RESULTS: One hundred twenty-six patients underwent open adrenalectomy and 30 patients underwent endoscopic adrenalectomy. The 2 groups were well matched for age, sex, lesion size, and stage (P = NS). The mean follow-up time was similar for the 2 groups (P = NS). The local recurrence rate was 19% for open adrenalectomy and 21% for endoscopic adrenalectomy, whereas distant metastases were recorded in 31% of patients in the conventional adrenalectomy group and 17% in the endoscopic adrenalectomy group (P = NS). The mean time to recurrence was 27 ± 27 months in the conventional open adrenalectomy group and 29 ± 33 months in the endoscopic adrenalectomy group (P = NS). No significant differences were found between the 2 groups in terms of 5-year disease-free survival (38.3% vs 58.2%) and 5-year overall survival rates (48% vs 67%; P = NS). CONCLUSION: The operative approach does not affect the oncologic outcome of patients with localized adrenocortical carcinoma, if the principles of surgical oncology are respected.

Adrenocortical carcinoma: effect of hospital volume on patient outcome.

PURPOSE: Optimal management of adrenocortical carcinoma (ACC) involves a detailed diagnostic workup, radical surgery, and appropriate adjuvant therapy. However, due to the rarity of this disease, adequate expertise is necessary to ensure optimal patient care. We evaluated if the experience of a treating center influences the outcome of ACC. METHODS: Two hundred sixty-three patients who underwent adrenalectomy for ACC were included in a multi-institutional surgical survey and divided into 2 groups: "high-volume center" (HVC) (≥10 adrenalectomies for ACC) and "low-volume center" (LVC) (<10 adrenalectomies for ACC). A comparative analysis was performed. RESULTS: One hundred seventy-two patients underwent adrenalectomy at HVC and 91 at LVC. The two groups were homogeneous for age, sex, clinical presentation, and stage. The mean lesions size of ACC was higher in HVC than in LVC (104.1 ± 54.6 vs 82.8 ± 41.3 mm; P < 0.001). A significantly higher rate of lymph node dissection (P < 0.01) and of multiorgan resection (P < 0.01) was accomplished in HVC. The number of patients who underwent adjuvant therapy was significantly higher in HVC (P < 0.001). Local recurrence rate was lower in patients treated at HVC (6% vs 18.5%; P = NS). Mean time to recurrence was significantly longer in HVC than in LVC (25.2 ± 28.1 vs 10.1 ± 7.5; P < 0.01). CONCLUSION: The expertise of dedicated centers had a positive impact on the outcome of patients with ACC, resulting in a lower recurrence rate and improved mean time to recurrence. The improved patient outcome could be related not only to the appropriateness of the surgical procedure, but also to a more adequate multidisciplinary approach.

High expression of dopamine receptor subtype 2 in a large series of neuroendocrine tumors.

AIM: To evaluate by immumohistochemistry the presence of DR subtype 2 (D2R) in well differentiated NETs of different sites and in normal islet cells. BACKGROUND: Recent data in vitro and in vivo support that dopaminergic drugs might exert an inhibitory effect on hormone secretion and, possibly, on tumor growth in neuroendocrine tumors (NET)s. Their potential therapeutic role needs the demonstration of dopamine receptors (DR) in tumor cells. Little is known on the expression of DR in NETs. RESULTS: 85% of samples (100% of bronchial carcinoids and 93% of islet cell tumors) showed positivity for D2R; intensity of immunoreaction in NETs was similar or higher than in pituitary (54% and respectively 31% of cases). D2R positivity in more than 70% of tumor cells was observed in 46% of samples. Same intensity of D2R-immunoreactivity was found in pituitary and normal islet cells. No differences in D2R expression were recorded on considering tumor grading, size, proliferative activity, presence of metastases, endocrine activity and gender. A significant difference (62.5% vs 96.4%, p = 0.039) was observed in the prevalence of D2R expression between patients with more aggressive tumors and patients without recurrence/progression of disease during follow-up. METHODS: 46 NET samples from 44 patients and normal endocrine pancreatic tissue were studied. D2R-staining was performed on NETs and compared with six non-secreting pituitary adenomas and related to clinical-pathological data. CONCLUSION: The present data demonstrate a high expression of D2R in NETs; this finding is of clinical relevance in view of the potential role of dopaminergic drugs in inhibiting secretion and/or cell proliferation in NETs.

Laparoscopic bilateral simultaneous adrenalectomy: results of 11 operations.

BACKGROUND: This study was undertaken to evaluate the outcomes of the simultaneous bilateral laparoscopic adrenalectomy. MATERIALS AND METHODS: This was a retrospective study, including 11 patients with bilateral adrenal lesions, affected by Cushing's syndrome (n=2), Cushing's disease (n=6), pheochromocytoma (n=2), and 1 adrenocorticotrophin-hormone-dependent hypercortisolism of unknown origin. RESULTS: Elevan bilateral adrenalectomies were carried out by the laparoscopic approach with no conversions. The operations were performed in 7 cases by the lateral transperitoneal adrenalectomy (LTLA), in 3 by the posterior approach (PRA), and in 1 by the combined approach. The mean size of the masses was 5 cm. (range, 4-13). The average operating time was 245 minutes for LTLA and 218 minutes for PRA (P<0.05). The estimated mean blood loss was 87+/-36 mL (range, 20-150). No patients required transfusions. The mean hospital stay was 5+/-1.8 days (range, 4-7). The mean follow-up was 34 months (range, 2-96). CONCLUSIONS: Our study confirms that the bilateral adrenalectomy by the minimally invasive technique is safe and effective, affording acceptable blood loss and morbidity with a short hospital stay.