Parathyroid carcinoma and atypical parathyroid tumor: analysis of an Italian database.

OBJECTIVE: Atypical parathyroid tumor (aPT) and parathyroid carcinoma (PC) are extremely rare parathyroid neoplasms, accounting together for <2% of all parathyroid tumors. They often present an overlapping clinical phenotype, sharing clinical, biochemical, and some histological features. They are distinguished only by the presence of local invasion, and lymph nodes or distant metastasis, which are all absent in aPTs. To date, only few studies have compared clinical presentation and features between aPTs and PCs. Our purpose was to conduct a retrospective study on a multicenter Italian database of aPT and PC patients. DESIGN AND METHODS: We comparatively analyzed main features of aPT (n = 57) and PC (n = 74) patients collected at 15 major endocrinology and endocrine surgery centers in Italy. RESULTS AND CONCLUSIONS: Atypical parathyroid tumors and PCs showed no significant differences in many clinical features and presented similar values of elevated parathyroid hormone and total serum calcium. Renal complications, namely nephrolithiasis and nephrocalcinosis, appeared to be more common in PC, with a significantly higher rate of renal colic, regardless of total serum calcium levels and 24-h calciuria. Parathyroid carcinomas showed significantly higher postoperative disease persistence and recurrence rates, presumably due to an uncomplete resection of the primary tumor in 23.5% of cases and/or presence of unremoved active metastasis, but they had similar disease-free mean time after surgery than aPT. To deepen the study of malignant parathyroid tumors, the institution of a novel Italian retro-prospective multicenter registry of aPTs and PCs is currently ongoing, and a dedicated PC European registry has been recently activated.

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.

Surgery for Sporadic Primary Hyperparathyroidism: Evolution over the Last Twenty Years in a Monocentric Setting.

The sporadic parathyroid pathology of surgical interest is primarily limited to lesions that are the cause of hormonal hyperfunction (primary hyperparathyroidism). In recent years, parathyroid surgery has evolved significantly, and numerous minimally invasive parathyroidectomy techniques have been developed. In this study, we describe a single-center and well-documented case series of sporadic primary hyperparathyroidism, surgically treated by a single operator in the Endocrine Surgery Unit of the Surgical Clinic of the University of Florence-Careggi University Hospital, recorded and updated in a dedicated database that embraces the entire evolutionary timeframe of parathyroid surgery. From January 2000 to May 2020, 504 patients with a clinical and instrumental diagnosis of hyperparathyroidism were included in the study. The patients were divided into two groups, based on the application of intraoperative parathyroid hormone (ioPTH). The analysis shows that the use of ioPTH with the rapid method could be ineffective in helping surgeons in primary operations, especially when ultrasound and scintiscan are concordant. The advantages obtained by not using intraoperative PTH are not only economic. In fact, our data shows shorter operating and general anesthesia times and hospital stays, having an important impact on patient biological commitment. Furthermore, the significant reduction in operating time makes it possible to almost triple the volume of activity in the same unit of time available, with an undeniable advantage for the reduction of waiting lists. In recent years, minimally invasive approaches have allowed surgeons to reach the best compromise between invasiveness and aesthetic results.

Early calcitonin levels in medullary thyroid carcinoma: Prognostic role in patients without distant metastases at diagnosis.

Introduction: Calcitonin is the most specific marker for medullary thyroid carcinoma, thus, low detectable calcitonin values after surgery can conceal persistent disease. The present study aimed to explore the prognostic role of pre-operative and early calcitonin levels in patients without distant metastases at diagnosis. Methods: A retrospective cohort of patients suffering from medullary thyroid carcinoma was considered (N=55). The final disease status, i.e. complete response (undetectable calcitonin levels and negative radiological assessments) or persistent disease (detectable calcitonin levels and/or positive radiological assessments), was deduced from the last available follow-up. Pre-operative and early calcitonin levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status. Results: Persistent disease patients showed higher pre-operative and early calcitonin values (p=0.028 and p<0.001, respectively), compared to complete response sub-cohort. Cox-regression models show that early detectable calcitonin increases up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (p=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early calcitonin level ≥16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, p<0.001). Conclusion: Calcitonin levels six months after surgery represents an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastasis at diagnosis.

Classic and Follicular Variant of Papillary Thyroid Microcarcinoma: 2 Different Phenotypes Beyond Tumor Size.

Context: Despite the wide revision of current guidelines, the management of papillary thyroid microcarcinoma (mPTC) still has to be decided case by case. There is conflicting evidence about the role of more frequent histological subtypes, and no data about potential differences at presentation. Objective: Our aim was to compare the phenotype of the 2 most frequent mPTC variants, namely, classical papillary thyroid microcarcinoma (mPTCc) and the follicular variant of papillary thyroid microcarcinoma (mFVPTC) . Methods: Retrospective observational study, from January 2008 to December 2017 of a consecutive series of patients with mPTCc and mFVPTC. All cases were classified according to the 2015 American Thyroid Association (ATA) risk classification. Clinical and preclinical features of mPTCc and mFVPTC at diagnosis were collected. The comparison was also performed according to the incidental/nonincidental diagnosis and differences were verified by binary logistic analysis. Results: In total, 235 patients were eligible for the analysis (125 and 110 mPTCc and mFVPTC, respectively). Compared with mPTCc, mFVPTCs were more often incidental and significantly smaller (4 vs 7 mm) (P < .001 all), possibly influenced by the higher rate of incidental detection. mFVPTC and incidental (P < .001 both) tumors were significantly more often allocated within the low-risk class. A logistic regression model, with ATA risk class as the dependent variable, showed that both mFVPTC (OR 0.465 [0.235-0.922]; P = .028]) and incidental diagnosis (OR 0.074 [0.036-0.163]; P < .001) independently predicted ATA risk stratification. Conclusion: mFVPTC shows some differences in diagnostic presentation compared with mPTCc, and seems to retain a significant number of favorable features, including a prevalent onset as incidental diagnosis.

Case Report: Adrenocortical Oncocytoma in a Patient with a Previous Contralateral Adrenalectomy for a Cortisol-Secreting Adenoma.

Background: Oncocytomas are uncommon benign tumors that arise in various organs and are predominantly composed of oncocytes. Adrenocortical oncocytomas are extremely rare and are generally non-functioning. Methods: We report the case of a 40-year-old patient with a progressively enlarging left adrenal mass. At the age of 19 he had undergone right adrenalectomy for a cortisol-secreting adenoma. Radiologic features were not typical of an adenoma and positive uptake was detected at 18F-FDG-PET. Because of the uncertain nature of the growing lesion, it was decided to proceed to surgical resection. Results: The surgeon managed to remove the left adrenal mass, sparing the normal adrenal gland, and histology was consistent with adrenocortical oncocytoma. Corticosteroid supplementation was prescribed, but at reassessment, adrenal function was found to be preserved and treatment withdrawn. Conclusions: Adrenal oncocytoma is a rare diagnosis, but should be considered in the presence of a growing mass with non-specific radiologic appearance.

Genetics and Epigenetics of Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is an extremely rare malignancy, accounting less than 1% of all parathyroid neoplasms, and an uncommon cause of primary hyperparathyroidism (PHPT), characterized by an excessive secretion of parathyroid hormone (PTH) and severe hypercalcemia. As opposed to parathyroid hyperplasia and adenomas, PC is associated with a poor prognosis, due to a commonly unmanageable hypercalcemia, which accounts for death in the majority of cases, and an overall survival rate of 78-85% and 49-70% at 5 and 10 years after diagnosis, respectively. No definitively effective therapies for PC are currently available. The mainly employed treatment for PC is the surgical removal of tumoral gland(s). Post-surgical persistent or recurrent disease manifest in about 50% of patients. The comprehension of genetic and epigenetic bases and molecular pathways that characterize parathyroid carcinogenesis is important to distinguish malignant PCs from benign adenomas, and to identify specific targets for novel therapies. Germline heterozygote inactivating mutations of the CDC73 tumor suppressor gene, with somatic loss of heterozygosity at 1q31.2 locus, account for about 50-75% of familial cases; over 75% of sporadic PCs harbor biallelic somatic inactivation/loss of CDC73. Recurrent mutations of the PRUNE2 gene, a recurrent mutation in the ADCK1 gene, genetic amplification of the CCND1 gene, alterations of the PI3K/AKT/mTOR signaling pathway, and modifications of microRNA expression profile and gene promoter methylation pattern have all been detected in PC. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of PC, in both familial and sporadic forms of this malignancy.

Morphologic evidence of telocytes in human thyroid stromal tissue.

Despite the evidence accumulated over the past decade that telocytes (TCs) are a distinctive, though long neglected, cell entity of the stromal microenvironment of several organs of the human body, to date their localization in the endocrine glands remains almost unexplored. This study was therefore undertaken to examine the presence and characteristics of TCs in normal human thyroid stromal tissue through an integrated morphologic approach featuring light microscopy and ultrastructural analysis. TCs were first identified by immunohistochemistry that revealed the existence of an intricate network of CD34+ stromal cells spread throughout the thyroid interfollicular connective tissue. Double immunofluorescence allowed to clearly differentiate CD34+ stromal cells lacking CD31 immunoreactivity from neighbour CD31+ microvascular structures, and the evidence that these stromal cells coexpressed CD34 and platelet-derived growth factor receptor α further strengthened their identification as TCs. Transmission electron microscopy confirmed the presence of stromal cells ultrastructurally identifiable as TCs projecting their characteristic cytoplasmic processes (i.e., telopodes) into the narrow interstitium between thyroid follicles and blood microvessels, where telopodes intimately surrounded the basement membrane of thyrocytes. Collectively, these morphologic findings provide the first comprehensive demonstration that TCs are main constituents of the human thyroid stroma and lay the necessary groundwork for further in-depth studies aimed at clarifying their putative implications in glandular homeostasis and pathophysiology.

Thyroidectomy for Cancer: The Surgeon and the Parathyroid Glands Sparing.

BACKGROUND: The diagnosis of thyroid cancer is continuously increasing and consequently the amount of thyroidectomy. Notwithstanding the actual surgical skill, postoperative hypoparathyroidism still represents its most frequent complication. The aims of the present study are to analyze the rate of postoperative hypoparathyroidism after thyroidectomy, performed for cancer by a single first operator, without any technological aid, and to compare the data to those obtained adopting the most recent technological adjuncts developed to reduce the postoperative hypoparathyroidism. METHODS: During the period 1997-2020 at the Endocrine Surgery Unit of the Department of Clinical and Experimental Medicine of the University of Florence, 1648 consecutive extracapsular thyroidectomies for cancer (401 with central compartment node dissection) were performed. The percentage of hypoparathyroidism, temporary or permanent, was recorded both in the first period (Group A) and in the second, most recent period (Group B). Total thyroidectomies were compared either with those with central compartment dissection and lobectomies. Minimally invasive procedures (MIT, MIVAT, some transoral) were also compared with conventional. Fisher's exact and Chi-square tests were used for comparison of categorical variables. p < 0.01 was considered statistically significant. Furthermore, a literature research from PubMed® has been performed, considering the most available tools to better identify parathyroid glands during thyroidectomy, in order to reduce the postoperative hypoparathyroidism. We grouped and analyzed them by technological affinity. RESULTS: On the 1648 thyroidectomies enrolled for the study, the histotype was differentiated in 93.93 % of cases, medullary in 4% and poorly differentiated in the remaining 2.06%. Total extracapsular thyroidectomy and lobectomy were performed respectively in 95.45% and 4.55%. We recorded a total of 318 (19.29%) cases of hypocalcemia, with permanent hypoparathyroidism in 11 (0.66%). In regard to the literature, four categories of tools to facilitate the identification of the parathyroids were identified: (a) vital dye; (b) optical devices; (c) autofluorescence of parathyroids; and (d) autofluorescence enhanced by contrast media. Postoperative hypoparathyroidism had a variable range in the different groups. CONCLUSIONS: Our data confirm that the incidence of post-surgical hypoparathyroidism is extremely low in the high volume centers. Its potential reduction adopting technological adjuncts is difficult to estimate, and their cost, together with complexity of application, do not allow immediate routine use. The trend towards increasingly unilateral surgery in thyroid carcinoma, as confirmed by our results in case of lobectomy, is expected to really contribute to a further reduction of postsurgical hypoparathyroidism.

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.

Choosing the best algorithm among five thyroid nodule ultrasound scores: from performance to cytology sparing-a single-center retrospective study in a large cohort.

OBJECTIVE: Incidental diagnosis of thyroid nodules, and therefore of thyroid cancer, has definitely increased in recent years, but the mortality rate for thyroid malignancies remains very low. Within this landscape of overdiagnosis, several nodule ultrasound scores (NUS) have been proposed to reduce unnecessary diagnostic procedures. Our aim was to verify the suitability of five main NUS. METHODS: This single-center, retrospective, observational study analyzed a total number of 6474 valid cytologies. A full clinical and US description of the thyroid gland and nodules was performed. We retrospectively applied five available NUS: KTIRADS, ATA, AACE/ACE-AME, EUTIRADS, and ACRTIRADS. Thereafter, we calculated the sensitivity, specificity, PPV, and NPV, along with the number of possible fine-needle aspiration (FNA) sparing, according to each NUS algorithm and to clustering risk classes within three macro-groups (low, intermediate, and high risk). RESULTS: In a real-life setting of thyroid nodule management, available NUS scoring systems show good accuracy at ROC analysis (AUC up to 0.647) and higher NPV (up to 96%). The ability in FNA sparing ranges from 10 to 38% and reaches 44.2% of potential FNA economization in the low-risk macro-group. Considering our cohort, ACRTIRADS and AACE/ACE-AME scores provide the best compromise in terms of accuracy and spared cytology. CONCLUSIONS: Despite several limitations, available NUS do appear to assist physicians in clinical practice. In the context of a common disease, such as thyroid nodules, higher accuracy and NPV are desirable NUS features. Further improvements in NUS sensitivity and specificity are attainable future goals to optimize nodule management. KEY POINTS: • Thyroid nodule ultrasound scores do assist clinicians in real practice. • Ultrasound scores reduce unnecessary diagnostic procedures, containing indolent thyroid microcarcinoma overdiagnosis. • The variable malignancy risk of the "indeterminate" category negatively influences score's performance in real-life management of thyroid lesions.

An easier option for "invisible scar" thyroidectomy: hybrid-transoral endoscopic thyroidectomy submental access (H-TOETSA)-experience on twenty-two consecutive patients.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is currently the only "cervical invisible scar" procedure with a surgical access close to the thyroid area. The aim of this technical note was to describe a hybrid technique with a vestibular and a submental access as applied in 22 consecutive patients undergoing lobectomy. METHODS: Out of 502 thyroidectomies performed from February 1, 2018 to May 31, 2019, feasibility of Hybrid-TransOral Endoscopic Thyroidectomy Submental Access (H-TOETSA) was assessed in 22 patients meeting the inclusion criteria. Differently from TOETVA, a central trocar (≤ 10 mm) for the camera was placed on the natural skin depression immediately under the chin. A left 3 mm and a right 5 mm (or 3 mm if a 3 mm energy device was available) trocars were placed in the vestibulum (as in TOETVA). RESULTS: Operative time was 74.32 (± 34.16) min. Two temporary recurrent nerve paralysis and three lip/chin dysesthesia were observed. In two patients, an additional 3 cm horizontal access was performed 2 cm above the clavicle to control a persistent bleeding. Patients complained pain only in the first postoperative hours. All patients perceived excellent cosmetic results even at postoperative day 1. CONCLUSION: H-TOETSA was feasible and resulted to have some technical and clinical advantages maintaining the purpose to avoid a visible scar on the neck.

In Vitro Control of Genes Critical for Parathyroid Embryogenesis by Extracellular Calcium.

BACKGROUND: The expression of the parathyroid transcription factors, encoded by the genes GATA3, GCM2, and MAFB, persists after parathyroid morphogenesis. This suggests a role of these genes in the regulatory program that governs parathyroid function in the adult. Indeed, these 3 genes form a transcriptional cascade able to activate PTH gene expression. MATERIALS AND METHODS: Adult adenoma parathyroid tissues were put in primary cell culture to evaluate the messenger ribonucleic acid (mRNA) expression of the PTH gene, of the genes involved in the calcium regulatory signaling pathway (CaSR, GNA11, and AP2S1), and of the 3 genes (GATA3, GCM2, and MAFB) involved in the parathyroid morphogenesis in the presence of different extracellular calcium concentrations from 0.1 mM to 3.0 mM. AIM: The aim of the study was to investigate whether different extracellular calcium conditions could control the expression of transcription factors critical for parathyroid embryogenesis. RESULTS: The results of the experiments showed that the mRNA expression of GATA3, GCM2, and MAFB genes follows the same response as the PTH gene to extracellular calcium concentrations, with the highest expression at low calcium (0.1 mM) and the lowest at high calcium (3.0 mM). Conversely, the genes involved in the calcium signaling in the parathyroid cells showed a variable response to the extracellular calcium concentrations, with the CaSR and GNA11 genes exhibiting a sensitivity to low calcium concentrations. CONCLUSIONS: These findings indicate that transcription factors recognized for their role in parathyroid embryogenesis show a response to extracellular calcium later in adulthood that parallels the behavior of the PTH gene.

The Clinical Value of Fluorescent Lymphography with Indocyanine Green During Robotic Surgery for Gastric Cancer: a Matched Cohort Study.

BACKGROUND: Near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) has been recently introduced for lymphatic mapping in several tumors. We aimed at investigating whether this technology may improve the intraoperative visualization of lymph nodes during robotic gastrectomy for gastric cancer. METHODS: Between June 2014 and June 2018, a total of 94 patients underwent robotic gastrectomy with D2 lymph node dissection for gastric cancer. In 37 patients, ICG was injected endoscopically into the submucosal layer around the tumor the day before surgery. After propensity score matching, the results of these 37 patients were compared with the results of 37 control patients who had undergone robotic gastrectomy without ICG injection. RESULTS: Among the 37 patients within the ICG group, no adverse events related to ICG injection or intraoperative NIR imaging occurred. After completion of D2 lymph node dissection, no residual fluorescent lymph nodes were left in the surgical field. A mean of 19.4 ± 14.7 fluorescent lymph nodes was identified per patient. The mean total number of harvested lymph nodes was significantly higher in the ICG group than in the control group (50.8 vs 40.1, P = 0.03). In the ICG group, 23 patients had metastatic lymph nodes. The accuracy, sensitivity, and specificity of ICG fluorescence for metastatic lymph nodes were 62.2%, 52.6%, and 63.0%, respectively. CONCLUSION: Our study indicates that NIR imaging with ICG may provide additional node detection during robotic surgery for gastric cancer. Unfortunately, this technique failed to show good selectivity for metastatic lymph nodes.

Characterization of a novel CDC73 gene mutation in a hyperparathyrodism-jaw tumor patient affected by parathyroid carcinoma in the absence of somatic loss of heterozygosity.

Hyperparathyrodism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder. Loss of function of the cell division cycle protein 73 homolog (CDC73) gene is responsible for the syndrome. This gene encodes an ubiquitously expressed 531 amino acid protein, parafibromin, that acts as a tumor suppressor. Loss of heterozygosity (LOH) of the CDC73 locus in many HPT-JT associated parathyroid tumors from patients with germline mutation is in accordance with Knudson's "two-hit" model for hereditary cancer. A 41-year-old man with mandible ossifying fibroma suffered from severe hypercalcemia due to parathyroid carcinoma (PC). Genetic analysis was performed to evaluate germinal and somatic CDC73 gene mutation as well as real-time qRT-PCR to quantify CDC73 mRNA, miR-155 and miR-664 expression levels. Immunohistochemistry and Western blotting (WB) assay were carried out to evaluate parafibromin protein expression. A novel heterozygous nonsense mutation, c.191-192 delT, was identified in the CDC73 gene. No CDC73 LOH was found in PC tissue, nor any differences in expression levels for CDC73 gene, miR-155 and miR-664 between PC and parathyroid adenoma control tissues. On the contrary, both immunohistochemistry and WB assay showed an approximate 90% reduction of parafibromin protein expression in PC. In conclusion, this study describes a novel germinal mutation, c.191-192 delT, in the CDC73 gene. Despite normal CDC73 gene expression, we found a significant decrease in parafibromin. We hypothesize that a gene silencing mechanism, possibly induced by microRNA, could play a role in determining somatic post-transcriptional inactivation of the wild type CDC73 allele.

HypoparaNet: A Database of Chronic Hypoparathyroidism Based on Expert Medical-Surgical Centers in Italy.

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.

Predictivity of clinical, laboratory and imaging findings in diagnostic definition of palpable thyroid nodules. A multicenter prospective study.

PURPOSE: To assess the role of clinical, biochemical, and morphological parameters, as added to cytology, for improving pre-surgical diagnosis of palpable thyroid nodules. METHODS: Patients with a palpable thyroid nodule were eligible if surgical intervention was indicated after a positive or suspicious for malignancy FNAC (TIR 4-5 according to the 2007 Italian SIAPEC-IAP classification), or two inconclusive FNAC at a ≥3 months interval, or a negative FNAC associated with one or more risk factor. Reference standard was histological malignancy diagnosis. Likelihood ratios of malignancy, sensitivity, specificity, negative (NPV), and positive predictive value (PPV) were described. Multiple correspondence analysis (MCA) and logistic regression were applied. RESULTS: Cancer was found in 433/902 (48%) patients. Considering TIR4-5 only as positive cytology, specificity, and PPV were high (94 and 91%) but sensitivity and NPV were low (61 and 72%); conversely, including TIR3 among positive, sensitivity and NPV were higher (88 and 82%) while specificity and PPV decreased (52 and 63%). Ultrasonographic size ≥3 cm was independently associated with benignity among TIR2 cases (OR of malignancy 0.37, 95% CI 0.18-0.78). In TIR3 cases the hard consistency of small nodules was associated with malignity (OR: 3.51, 95% CI 1.84-6.70, p < 0.001), while size alone, irrespective of consistency, was not diagnostically informative. No other significant association was found in TIR2 and TIR3. CONCLUSIONS: The combination of cytology with clinical and ultrasonographic parameters may improve diagnostic definition of palpable thyroid nodules. However, the need for innovative diagnostic tools is still high.

Cost-benefit analysis of the intraoperative parathyroid hormone assay in primary hyperparathyroidism.

BACKGROUND: The purpose of this study was to evaluate the usefulness of the routine intraoperative intact parathyroid hormone (IOPTH) assay, the role of unilateral and bilateral cervical exploration and of preoperative imaging, and to do a cost-benefit analysis in parathyroidectomy for primary hyperparathyroidism. METHODS: Two hundred sixty-four patients who underwent operations between January 2000 and March 2015 were retrospectively divided into 2 groups. RESULTS: Group A (IOPTH) was composed of 64 patients. Ultrasonography and technetium-99m-sestamibi (MIBI) identified the adenoma in 38 cases. Bilateral exploration was performed in 43 patients; of which 2 failures occurred. The IOPTH false-negative rate was 18.4%. The average cost was €1297.30. Group B (without IOPTH) was composed of 200 patients. Ultrasonography and MIBI identified the adenoma in 113 cases. Bilateral exploration was performed in 129 patients; of which 2 failures occurred. The average cost was €618.75. CONCLUSION: The IOPTH assay should be used only in few selected cases because of its high cost. The experience of the team is essential to obtain a high cure rate. © 2016 Wiley Periodicals, Inc. Head Neck 39: 241-246, 2017.

Robotic rectal surgery: State of the art.

Laparoscopic rectal surgery has demonstrated its superiority over the open approach, however it still has some technical limitations that lead to the development of robotic platforms. Nevertheless the literature on this topic is rapidly expanding there is still no consensus about benefits of robotic rectal cancer surgery over the laparoscopic one. For this reason a review of all the literature examining robotic surgery for rectal cancer was performed. Two reviewers independently conducted a search of electronic databases (PubMed and EMBASE) using the key words "rectum", "rectal", "cancer", "laparoscopy", "robot". After the initial screen of 266 articles, 43 papers were selected for review. A total of 3013 patients were included in the review. The most commonly performed intervention was low anterior resection (1450 patients, 48.1%), followed by anterior resections (997 patients, 33%), ultra-low anterior resections (393 patients, 13%) and abdominoperineal resections (173 patients, 5.7%). Robotic rectal surgery seems to offer potential advantages especially in low anterior resections with lower conversions rates and better preservation of the autonomic function. Quality of mesorectum and status of and circumferential resection margins are similar to those obtained with conventional laparoscopy even if robotic rectal surgery is undoubtedly associated with longer operative times. This review demonstrated that robotic rectal surgery is both safe and feasible but there is no evidence of its superiority over laparoscopy in terms of postoperative, clinical outcomes and incidence of complications. In conclusion robotic rectal surgery seems to overcome some of technical limitations of conventional laparoscopic surgery especially for tumors requiring low and ultra-low anterior resections but this technical improvement seems not to provide, until now, any significant clinical advantages to the patients.