Hemithyroidectomy versus total thyroidectomy in the intermediate-risk differentiated thyroid cancer: the Italian Societies of Endocrine Surgeons and Surgical Oncology Multicentric Study.

The surgical treatment of the intermediate-risk DTC (1-4 cm) remains still controversial. We analyzed the current practice in Italy regarding the surgical management of intermediate-risk unilateral DTC to evaluate risk factors for recurrence and to identify a group of patients to whom propose a total thyroidectomy (TT) vs. hemithyroidectomy (HT). Among 1896 patients operated for thyroid cancer between January 2017 and December 2019, we evaluated 564 (29.7%) patients with unilateral intermediate-risk DTC (1-4 cm) without contralateral nodular lesions on the preoperative exams, chronic autoimmune thyroiditis, familiarity or radiance exposure. Data were collected retrospectively from the clinical register from 16 referral centers. The patients were followed for at least 14 months (median time 29.21 months). In our cohort 499 patients (88.4%) underwent total thyroidectomy whereas 65 patients (11.6%) underwent hemithyroidectomy. 151 (26.8%) patients had a multifocal DTC of whom 57 (10.1%) were bilateral. 21/66 (32.3%) patients were reoperated within 2 months from the first intervention (completion thyroidectomy). Three patients (3/564) developed regional lymph node recurrence 2 years after surgery and required a lymph nodal neck dissection. The single factor related to the risk of reoperation was the histological diameter (HR = 1.05 (1.00-1-09), p = 0.026). Risk stratification is the key to differentiating treatment options and achieving better outcomes. According to the present study, tumor diameter is a strong predictive risk factor to proper choose initial surgical management for intermediate-risk DTC.

Modulating the extension of thyroidectomy in patients with papillary thyroid carcinoma pre-operatively eligible for lobectomy: reliability of ipsilateral central neck dissection.

PURPOSE: Pre-operative work-up and macroscopic intraoperative inspection could overlook occult central neck nodal metastases in patients with papillary thyroid carcinoma (PTC). An occult N1a status is able to change the initial risk stratification in small, clinically unifocal PTC potentially scheduled for thyroid lobectomy (TL) making total thyroidectomy (TT) the preferable option. We aimed to verified the reliability of an intraoperative management protocol based on frozen section examination (FSE) of ipsilateral central neck nodes (IpsiCND) to identify, among patients scheduled for TL, those who could benefit of a more extensive surgical resection (TT plus bilateral central neck dissection -CND-). METHODS: Thirty PTC patients preoperatively classified as T1N0 underwent TL plus IpsiCND-FSE (TL-group). In case of positive FSE, TT plus bilateral CND was accomplished during the same surgical procedure. A comparative analysis was performed between TL-group and a control group (C-group), who underwent TT plus IpsiCND-FSE, matched by a propensity score analysis. RESULTS: Nodal metastases (>2 mm) were found at final histology in 5/30 patients in the TL-group and in 6/30 in the C-group (p = 1.00). Micrometastases (≤2 mm) were retrieved in 5/30 TL-group patients and in 4/30 C-group patients (p = 1.00). Final histology staged as pN1a 10 (33.3%) patients for each group. FSE correctly identified five patients with occult nodal metastases >2 mm (16.6%) in TL-group, who underwent TT plus bilateral CND during the same surgical procedure. No permanent complications occurred. At a mean follow-up of 22.2 months, no local and/or nodal recurrence were observed. CONCLUSIONS: Intraoperative assessment of N status obtained with IpsiCND plus FSE allows for an accurate risk stratification. IpsiCND plus FSE real time modulated thyroidectomy seems a safe and effective surgical strategy reducing the need of a subsequent completion surgery and, theoretically, the risk of local recurrence.

Total thyroidectomy alone versus ipsilateral versus bilateral prophylactic central neck dissection in clinically node-negative differentiated thyroid carcinoma. A retrospective multicenter study.

BACKGROUND: Central neck dissection (CND) remains controversial in clinically node-negative differentiated thyroid carcinoma (DTC) patients. The aim of this multicenter retrospective study was to determine the rate of central neck metastases, the morbidity and the rate of recurrence in patients treated with total thyroidectomy (TT) alone or in combination with bilateral or ipsilateral CND. METHODS: The clinical records of 163 clinically node-negative consecutive DTC patients treated between January 2008 and December 2010 in three endocrine surgery referral units were retrospectively evaluated. The patients were divided into three groups: patients who had undergone TT alone (group A), TT with ipsilateral CND (group B), and TT with bilateral CND (group C). RESULTS: The respective incidences of transient hypoparathyroidism and unilateral recurrent nerve injury were 12.6% and 1% in group A, 23.3% and 3.3% in B, and 36.7% and 0% in C. Node metastases were observed in 8.7% in group A, 23.3% in B, and 63.3% in C. Locoregional recurrence was observed in 3.9% of patients in group A and in 0% in B and C. CONCLUSIONS: We found no statistically significant differences in the rates of locoregional recurrence between the three groups. Therefore, TT appears to be an adequate treatment for these patients; CND is associated with higher rates of transient hypoparathyroidism and cannot be considered the treatment of choice even if it could help for more appropriate selection of patients for RAI. Ipsilateral CND could be an interesting option considering the lower rate of hypocalcemia to be validated by further studies.

Yada: a novel tool for molecular docking calculations.

Molecular docking is a computational method employed to estimate the binding between a small ligand (the drug candidate) and a protein receptor that has become a standard part of workflow in drug discovery. Generally, when the binding site is known and a molecule is similar to known ligands, the most popular docking methods are rather accurate in the prediction of the geometry. Unfortunately, when the binding site is unknown, the blind docking analysis requires large computational resources and the results are often not accurate. Here we present Yada, a new tool for molecular docking that is capable to distribute efficiently calculations onto general purposes computer grid and that combines biological and structural information of the receptor. Yada is available for Windows and Linux and it is free to download at www.yada.unisa.it .

Improved biomonitoring of airborne contaminants by combined use of holm oak leaves and epiphytic moss.

Concentrations of 12 elements (Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb and Zn) and 16 EPA-listed PAHs were detected in Quercus ilex leaves and the epiphytic moss Leptodon smithii collected at urban, periurban and extraurban holm oak stands, in two Italian Regions (Campania and Tuscany). Levels of environmental contaminants were generally higher in leaves and moss from urban areas than periurban and extraurban ones and samples from Campania had the highest PAH content. The epiphytic moss accumulated higher concentrations of trace elements than leaves and the latter showed a higher accumulation capability for PAHs, especially for those with low molecular weight. The different bioaccumulation in leaves and moss were explained in terms of their distinctive morphological and ecophysiological characteristics. The combined approach seems a promising tool for the monitoring of a wide range of pollutants in Mediterranean urban and extraurban environments.

Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involvement in benign surface epithelial ovarian tumours.

A detailed long range restriction map of the region defined by markers D6S149 and D6S193 on chromosome 6q27 has been constructed. This was achieved by YAC cloning and contig assembling of the same region. Seven YAC clones were found to span the almost 1000 Kb region flanked by the two markers which on the genetic map resulted to be 1.9 cM apart. With some of the characterized YAC clones we undertook a molecular cytogenetic analysis of 20 benign ovarian tumors. The rationale for this was the recent mapping to a region of chromosome 6q27, flanked by markers D6281 and D6S133, of a locus for the SV40-mediated immortalization of human cells (SEN6 gene). Noteworthy we found that the the D6S149-D6S193 region (comprised in the larger D6S281-D6S133 physical interval) was altered in all samples analysed adding support to the occurrence of a immortalization step in this type of tumors.

Genomic structure and organization of kringles type 3 to 10 of the apolipoprotein(a) gene in 6q26-27.

Apolipoprotein(a) [apo(a)] is a highly polymorphic glycoprotein covalently linked to the apolipoprotein B-100 of LDL in a particle called lipoprotein(a) [Lp(a)]. High plasma levels of Lp(a) are associated with coronary as well as peripheral atherosclerosis. Plasma levels of Lp(a) show a remarkable variation ranging from 0.1 mg/dl to over 100 mg/dl. The apo(a) gene shows a size polymorphism which resides in the variable number of kringle domains which resemble plasminogen kringle IV. Ten different types of kringle IV repeats have been described, nine of which (kringle IV type 1 and type 3-10) are each supposed to be present in a single copy. The other kringles, namely kringle IV type 2 repeats, vary in number from 3 to 42 between apo(a) alleles and form the basis for the apo(a) size polymorphism. Although an inverse relationship has been observed between the number of kringle type 2 repeats and plasma levels of Lp(a), there are exceptions to this general finding. Indeed, several individuals have been described with similar apo(a) size alleles but very different plasma levels of Lp(a). Genetic studies have linked these differences to the apo(a) locus on 6q26-27, outlining the importance, besides the kringle type 2 repeats, of other regions of the apo(a) gene in contributing to the interindividual differences in the plasma concentration of Lp(a). One of the candidate regions is represented by the non-repeated type-3 to type-10 kringles which are invariably present in each apo(a) allele and whose structural integrity is playing a critical role in the correct assembly of the Lp(a) particle. Biochemical studies with recombinant wild type and mutagenized apo(a) cDNAs with several alterations of the non-repeated kringles have well documented this latter point. As a starting point to search for genetic variations in these kringles associated with different levels of Lp(a), we are presenting the genome organization of type-3 to 10 kringle along with specific PCR primers for easy analysis from genomic DNA. Restriction as well as partial sequencing analyses of the type-3 to 10 kringles region has also provided interesting clues as to the different evolutionary origin of these types of kringle with respect to the polymorphic type-2 kringles.

Mammalian Rh/T2/S-glycoprotein ribonuclease family genes: cloning of a human member located in a region of chromosome 6 (6q27) frequently deleted in human malignancies.

We describe the cloning of a novel human gene belonging to the Rh/T2/S-glycoprotein class of extracellular ribonucleases. This gene is present in a single copy in the human genome and has been mapped to 6q27, a region of the human genome prone to rearrangements associated with several human malignancies. The predicted open reading frame of the human cDNA encodes a protein of 191 amino acids, and the pattern of expression is ubiquitous. Some of the sequence features of this gene, in particular those corresponding to the bipartite RNase motif of the active site, are perfectly conserved between distant species such as human and the plant Lycopersicon esculentum. No mammalian homologues have been described so far, and this report presents for the first time both the human and the mouse sequences of the corresponding members of this class of highly conserved extracellular ribonucleases.

Scaglietti's method for conservative treatment of simple bone cysts with local injections of methylprednisolone acetate.

The results of 30 consecutive cases of simple bone cysts treated conservatively by intracystic injections of methylprednisolone acetate (MPA) according to the method of Scaglietti are reported. The injections were given under general or local anaesthesia in doses of 80-200 mgs repeated every 2 months up to a total of 2 or 3 injections, rarely more. The minimum period required for achieving a result is 6 months; but there is a continuation of radiographic improvement for 1 to 2 years. There is complete radiographic cure in about half the cases; in the others there is a substantial improvement which makes surgery unnecessary. We have used this method systematically for 3 years, and out of 42 cases only one required operation because of a displaced subtrochanteric fracture. There was a partial recurrence in one case after apparent radiographic cure. The patients' age does not seem to affect the result but we gained the impression that the effect of MPA is quicker and more reliable in younger patients. Although we do not understand the mechanism of cure in this method it has undoubted advantages over surgery.