Grey-scale analysis improves the ultrasonographic evaluation of thyroid nodules

Ultrasonography is the main imaging method for the workup of thyroid nodules. However, interobserver agreement reported for echogenicity and echotexture is quite low. The aim of this study was to perform quantitative measurements of the degree of echogenicity and heterogeneity of thyroid nodules, to develop an objective and reproducible method to stratify these features to predict malignancy.A retrospective study of patients undergoing ultrasonography-guided fine-needle aspiration was performed in an University hospital thyroid center. From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided fine-needle aspiration. In a single ultrasound image, 3 regions of interest (ROIs) were drawn: the first including the nodule; the second including a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, expressing the median, mean, and SD of the gray levels of the pixels comprising each region. Echogenicity was expressed as a ratio: the nodule/parenchyma, the nodule/muscle, and parenchyma/muscle median gray ratios were calculated. The heterogeneity index (HI) was calculated as the coefficient of variation of gray histogram for each of the 3 ROIs. Cytology and histology reports were recorded.Nodule/parenchyma median gray ratio was significantly lower (more hypoechoic) in nodules found to be malignant (0.45 vs 0.61; P = 0.002) and can be used as a continuous measure of hypoechogenicity (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.03-0.49). Using a cutoff derived from ROC curve analysis (<0.46), it showed a substantial inter-rater agreement (k = 0.74), sensitivity of 56.7% (95% CI 37.4-74.5%), specificity of 72.0% (67.8-75.9%), positive likelihood ratio (LR) of 2.023 (1.434-2.852), and negative LR of 0.602 (0.398-0.910) in predicting malignancy (diagnostic odds ratio 3.36; 1.59-7.10). Parenchymal HI was associated with anti-thyroperoxidase positivity (OR 19.69; 3.69-105.23). The nodule HI was significantly higher in malignant nodules (0.73 vs 0.63; P = 0.03) and, if above the 0.60 cutoff, showed sensitivity of 76.7% (57.7-90.1%), specificity of 46.8% (42.3-51.4%), positive LR of 1.442 (1.164-1.786), and negative LR of 0.498 (0.259-0.960).Evaluation of nodule echogenicity and echotexture according to a numerical estimate (nodule/parenchyma median gray ratio and nodule HI) allows for an objective stratification of nodule echogenicity and internal structure

Vitiligo and autoimmune thyroid disorders

Vitiligo represents the most common cause of acquired skin, hair and oral depigmentation, affecting 0.5-1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated to other rare systemic disorders due to presence of melanocytes in other body districts, such as in the eyes, auditory, nervous and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s)

CTLA-4 and PD-1 ligand gene expression in epithelial thyroid cancers

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1, PD-L2, CD80 and CD86 was evaluated at mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the down-regulation of CD80 was observed in above all ATC. In addition, the increased expression of CD80 associated to longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAFV600E mutation in PTC. The increased PD-L2 expression correlated with BRAFV600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 down-regulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC

Thyroglobulin measurement in the washout of fine needle aspirates for the diagnosis of suspicious cervical lymph nodes

Ultrasound-guided fine-needle aspiration cytology (FNAC) for suspicious cervical lymph nodes (CLN) is the gold standard technique for the identification of metastases from differentiated thyroid carcinomas. Thyroglobulin protein (Tgp) assay in the washout of needles employed for FNA biopsies (FNAB) has been reported to refine and support FNAC performances, especially in cases of inadequate sampling or cystic lymph nodes. In the present work, we evaluated the usefulness of routine measurement of Tgp in the FNAB washout of suspicious cervical lymph nodes (CLN), and its ability to increase the FNAC accuracy in the diagnosis of metastatic CLN. A case study of 45 CLN with histological diagnosis from 36 patients was analyzed. Histology showed metastases from papillary thyroid carcinomas (PTC) in 31 CLN, from anaplastic thyroid cancer (ATC) in 3 CLN, from medullary thyroid cancer (MTC) in 4 CLN, and metastases from extrathyroidal malignancies in 5 CLN. Two CLN analyzed were found to be non-neoplastic. The overall accuracy of FNAC was 82.9%, and that of Tgp was 91.1%, not statistically different. However, Tgp determination was found essential in 4 cases of metastatic CLN from DTC with inadequate cytology, and in 1 case in which the FNAC provided a false negative result. We demonstrated that FNAC and Tgp assay show similar diagnostic accuracies, and that Tgp measurement may represent the only available information in case of inadequate lymph node sampling or cystic lymph nodes

Evaluation of Clinicopathological and Molecular Parameters on Disease Recurrence of Papillary Thyroid Cancer Patient: A Retrospective Observational Study

The American Joint Committee on Cancer has revised the Tumor-Node-Metastasis (TNM) staging system for papillary thyroid cancer (PTC) patients. We examined the impact of this new classification (TNM-8) on patient stratification and estimated the prognostic value of clinicopathological features for the disease-free interval (DFI) in a cohort of 1148 PTC patients. Kaplan-Meier analyses showed that all clinicopathological parameters analyzed, except age and multifocality, were associated significantly with DFI. Cox regression identified tall cell PTC variant and stage as independent risk factors for DFI. When the stage was replaced with age, tumor size, and lymph node (LN) metastases in the set of covariates, the lateral LN metastases stood out as the strongest independent predictor of DFI, followed by tall cell variant and age. A noteworthy result emerging from these analyzes is that regression models had lower Akaike and Bayesian information criterions if variables were categorized based on the TNM-7. In addition, we examined data from a different PTC patient cohort, acquired from The Cancer Genome Atlas database, to verify whether the DFI prediction could be enhanced by further clinicopathological and molecular parameters. However, none of these was found to be a significant predictor of DFI in the Cox model

Valutazione dei parametri clinico-patologici in una casistica di 1148 pazienti affetti da carcinoma papillifero della tiroide

Background: Le Linee Guida Internazionali, riportano numerose variabili capaci di predire il rischio di recidive e la ripresa della malattia. L'obiettivo è quello di valutare i parametri a disposizione, in un’ampia casistica di pazienti affetti da carcinoma papillifero della tiroide, come migliori indici per determinare l’intervallo libero da malattia ed il rischio di recidiva dopo chirurgia tiroidea. Materiali e Metodi: Sono stati arruolati 1148 pazienti sottoposti a intervento di tiroidectomia per carcinoma papillifero della tiroide dal 1995 al 2018. Per ogni paziente sono stati valutati: sesso; età; varianti del carcinoma; tiroidite autoimmune; TNM e stadiazione; multifocalità; invasione capsulare; infiltrazione muscolare; invasione vascolare; recidiva di malattia e follow-up. Risultati: Le curve di Kaplan-Meier mostrano riduzione dell’intervallo libero da malattia in presenza di: sesso maschile (P=0,001); variante sclerosante (P&lt;0,001); T3 (P=0,002); N1b (P&lt;0,001); stadio II (P&lt;0,001); invasione capsulare (P=0,001); infiltrazione muscolare (P=0,006); invasione vascolare (P&lt;0,001); multifocalità (P=0,049). Le analisi univariate, dimostrano che il rischio di recidiva è associato al genere maschile (p=0,002), alla variante sclerosante (p=0,0001), alla maggiore dimensione del tumore (p=0,001), alla presenza di ripetizioni metastatiche a livello linfonodale (p&lt;0,0001), all’invasione della capsula (p=0,001), all’infiltrazione muscolare (p=0,003) ed all’invasione vascolare (p=0,003). L’analisi multivariata evidenzia che la multifocalità (HR = 2,45; p&lt;0,02), la variante sclerosante (HR=2,82; p&lt;0,02) e l’invasione della capsula (HR=3,39; p&lt;0,001) rappresentano fattori di rischio indipendenti per lo sviluppo di recidive da carcinoma papillifero della tiroide. Conclusioni: I dati di questo studio evidenziano che la presenza della multifocalità, della variante istologica sclerosante e dell’invasione capsulare rappresentano dei parametri utili per una stratificazione prognostica dei pazienti affetti da carcinoma papillifero della tiroide

Central neck dissection in papillary thyroid carcinoma: results of a retrospective study.

Aims of the study: The aim of this retrospective study was to appraise the impact of central neck dissection (CND) when treating papillary thyroid carcinoma (PTC) and identifying predictors of tumour recurrence by analysing the results and complications related to this surgical procedure. Materials and methods: The study examined the histories of 347 patients with PTC, divided into two groups: group A including 284 patients who underwent total thyroidectomy (TT) only; group B including 63 patients who underwent TT and CND and possible lateral neck dissection (LND). Results: The patients in the B group were younger than those in the A group (an average of 44.5 vs. 48.6; p ¼ 0.03) and their tumours were larger (1.91 cm vs 1.27 cm, p ¼ 0.001). Multifocality, extra-capsular extensions of the neoplastic mass and high cell histological variant were more prevalent in the B group. The incidence of permanent hyperparathyroidism was higher in group B than in group A (25.4% vs 9.5%, p ¼ 0.0006). Recurrence of disease and the numbers requiring reoperation were also higher in group B: (24.1% in group B vs 6.6 in group A, p < 0.0001). Patients classified as clinically N0 at their first operation and who were most probably clinically N1, totalled 6.6%. Conclusions: Our data show that only extra-capsular extension may be considered a predictor of recurrence. The findings of our study support the idea of carrying out “therapeutic” CND only in cases of preoperative or macroscopic intraoperative clinical evidence of lymph-node involvement.Aims of the study: The aim of this retrospective study was to appraise the impact of central neck dissection (CND) when treating papillary thyroid carcinoma (PTC) and identifying predictors of tumour recurrence by analysing the results and complications related to this surgical procedure. Materials and methods: The study examined the histories of 347 patients with PTC, divided into two groups: group A including 284 patients who underwent total thyroidectomy (TT) only; group B including 63 patients who underwent TT and CND and possible lateral neck dissection (LND). Results: The patients in the B group were younger than those in the A group (an average of 44.5 vs. 48.6; p ¼ 0.03) and their tumours were larger (1.91 cm vs 1.27 cm, p ¼ 0.001). Multifocality, extra-capsular extensions of the neoplastic mass and high cell histological variant were more prevalent in the B group. The incidence of permanent hyperparathyroidism was higher in group B than in group A (25.4% vs 9.5%, p ¼ 0.0006). Recurrence of disease and the numbers requiring reoperation were also higher in group B: (24.1% in group B vs 6.6 in group A, p < 0.0001). Patients classified as clinically N0 at their first operation and who were most probably clinically N1, totalled 6.6%. Conclusions: Our data show that only extra-capsular extension may be considered a predictor of recurrence. The findings of our study support the idea of carrying out “therapeutic” CND only in cases of preoperative or macroscopic intraoperative clinical evidence of lymph-node involvement

Enucleation for gastrointestinal stromal tumors at the esophagogastric junction: Is this an adequate solution?

The authors discussed the proposal by Coccolini and colleagues to treat gastrointestinal stromal tumors (GISTs) at the esophagogastric junction with enucleation and, if indicated, adjuvant therapy, reducing the risks related to esophageal and gastroesophageal resection. They concluded that, because the prognostic impact of a T1 high-mitotic rate on esophageal GIST is worse than that of a T1 high-mitotic rate on gastric GIST, enucleation may not be an adequate surgery for esophagogastric GISTs with a high mitotic rate in which the guarantee of negative resection margins and adjuvant therapies can be the only chance of survival

Resection vs radiofrequency ablation for HCC from 3 to 5 cm: A single centre experience on 101 child- pugh class A-B naive patients

Background: The optimal therapy for HCC seems to be transplantation. For all those patients not eligible for transplantation (or waiting for it) the treatment of choice has been restricted in the last years to resection (RES) or radiofrequency ablation (RFA). RFA is supposed to lose part of its efficacy for HCC ranging over 3 cm. ltuly S108 POSTERS Aim of this study is to compare RFA to RES in a restricted cohort of patients with a first diagnosis of single HCC ranging from 3 to 5 cm and with not end stage liver disease. Patients and Methods: 10 I patients never treated before were enrolled. Those patients whose HCC position required too parenchimal lost at RES (central or close to main vascular structures) were treated with RFA (60), others underwent RES (41). The two groups were similar for HCC size (mean RES:RFA = 40:36 mm) and liver disease status. The outcome was considered in terms of overall survival (O.S.) and disease free survival (DFS) calculated with Kaplan-Meier method. Differences among groups were validated by Log-rank test. Results: O.S.% in RESIRFA at I, 2, 3, 4, 5 years: 91/96, 72177, 55153, 45135,42130. DFS% in RESIRFA at I, 2, 3, 4, 5 years: 76167,44142, 3511 8, 18113, 1510. Even if RES group seems to present a better long term O.S. and DFS this difference does not reach a statistical significance. Patients with worse Child-Pugh score (B vs A) and patients that have a recurrence within the first 12 month after treatment show a worse long term survival. Conclusion: It seems that Resection and RFA have the same efficacy in treating HCC ranging from 3 to 5 cm. Survival may be mostly related to nature of HCC itself and to liver disease on the background. A larger sample size is required to confirm this observation