Prediction of the Aggressive Clinical Course of Papillary Thyroid Carcinoma Based on Fine Needle Aspiration Biopsy Molecular Testing.

Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcomes, which opens up new avenues for using them in the personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in the preoperative diagnosis of aggressive variants of papillary thyroid cancer. The molecular genetic profile (expression levels of 34 different markers and BRAF mutations) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, fibronectin 1 (FN1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) genes. A weak statistical correlation (0.0015 < p < 0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, FN1, and CDKN2A genes.

Tension-free thyroidectomy (medial thyroidectomy)-a prospective study: surgical technique and results of 259 operations.

Background: Thyroid surgery is associated with a number of surgical complications including recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. The existing methods share the same principle-the mobilization of the thyroid from the lateral side. The aim of this study was to evaluate the safety of a novel technique of thyroidectomy-tension-free thyroidectomy (TFT) based on the medial approach to the laryngeal nerves and parathyroid glands (PTGs). Methods: The study was conducted between August 2021 and July 2022 in Saint Petersburg State University Hospital. A total of 261 patients with thyroid diseases were enrolled in the study and operated on using the TFT technique. Results: The operations with the use of TFT technique were completed in all but two cases which required the conversion to the standard lateral approach. Of 259 TFT cases unilateral laryngeal paresis was registered in 6 (2.3%) cases or in 1.7% of the number of RLNs at risk. In all but one case the vocal fold function recovered in less than 6 months of the follow-up. Among 87 patients who underwent total thyroidectomy transient postoperative hypoparathyroidism was found in 10 cases (11.5%), rate of persistent hypoparathyroidism was 0%. One case of postoperative bleeding was recorded (0.4%). Conclusions: The TFT technique demonstrated high safety and several advantages over the traditional method of performing operations on the thyroid gland.

New Opportunities for Preoperative Diagnosis of Medullary Thyroid Carcinoma.

The preoperative diagnostics of medullary thyroid carcinoma (MTC), including the measuring of the blood calcitonin level, has a number of limitations. Particular focus has recently been placed on the role of miRNAs in the development of various malignant tumors; a comparative analysis of accuracy of the existing methods for MTC diagnosis with a novel diagnosis method, evaluation of the miRNA-375 expression level, was performed in this study. The expression level of miRNA-375 in cytology samples from 555 patients with the known histological diagnosis, including 41 patients with confirmed postoperative diagnosis of MTC, was assessed. The diagnostic parameters of the basal calcitonin level, calcitonin in wash-out fluid from the FNAB needle, and miRNA-375 were compared. An assessment of the miRNA-375 expression level made it possible to detect all the MTC samples with a 100% accuracy among all the 555 cytology specimens, as well as in non-informative FNAB specimens, and specimens from the ipsilateral thyroid lobe. Parameters such as sensitivity, specificity, PPV, and NPV were 100%. The miRNA-375 level, unlike calcitonin, does not correlate with tumor volume, so it does not have the so-called "gray zone". An assessment of the miRNA-375 expression allows one to accurately distinguish MTC from other malignant and benign thyroid tumors.

Persistence of primary hyperparathyroidism: a single-center experience.

BACKGROUND: Parathyroidectomy is the only definitive treatment for primary hyperparathyroidism (PHPT). Precise localization of abnormal glands is a key to a successful surgery. Most patients are expected to be successfully treated with focused parathyroidectomy. However, this approach is associated with a risk of existing multiglandular disease which may lead to the postoperative persistence of PHPT. METHODS: Eight hundred ten patients who underwent an initial surgery for PHPT at SPBU Hospital in 2017-2018 were included in the study. Preoperative imaging results were evaluated. Multivariate logistic regressions were calculated to estimate predictive values of preoperative data for the risk of postoperative persistence and risk of MGD. RESULTS: Multiglandular disease was found to be a leading cause of persistent hyperparathyroidism. An anamnesis of thyroid surgery was found to be a significant risk factor for the persistence of hyperparathyroidism. The rate of persistence did not differ significantly between groups with bilateral neck exploration and focused parathyroidectomy. Age, sex, body mass index as well as negative results of preoperative US, MIBI, and 4D CT were not independently associated with a higher risk of MGD. All preoperative imaging modalities showed from low to moderate sensitivity for the detection of MGD. The frequency of cases of a missed second adenoma did not differ significantly between patients with concordant and discordant preoperative data. There were 7 cases with previously unsuspected second adenomas found solely due to bilateral neck exploration. CONCLUSIONS: None of the combination of preoperative visualization modalities was able to rule out the MGD and reliably identify patients for focused parathyroidectomy. Additional preoperative visualization failed to improve overall results. Bilateral neck exploration appeared to have a slight benefit for the patients with concordant preoperative imaging results.

Tension-free thyroidectomy (TFT): initial report.

The safety of thyroid surgery in terms of recurrent laryngeal nerve palsy and hypoparathyroidism has increased over the last decade. In this study, we present a new method of tension-free thyroidectomy (TFT), which could be used to further decrease the complication rate after a thyroidectomy. The procedure is based on the medial approach to the recurrent laryngeal nerve and the parathyroid glands after the division of the isthmus and successive complete dissection of Berry's ligament. In total, 92 patients (127 nerves at risk) underwent "tension-free thyroidectomy" (TFT) between August and November 2021. All the procedures were performed by a single surgeon at Saint Petersburg State University Hospital. There were 74 females and 18 male patients (ratio 4.1:1) with a mean age of 46.9 (range from 17 to 74). A lobectomy was carried out in 57 (62%) patients and a total thyroidectomy in 35 (38%). In 27 cases, patients additionally underwent central and/or lateral neck dissection. Indications for surgery were papillary carcinoma (N = 34), medullary cancer (N = 2), follicular neoplasia (N = 43), Grave's disease (N = 9), multinodular toxic goiter (N = 3), and multinodular nontoxic goiter (N = 1). Mean thyroid volume was 24.6 ml (ranged 12-70 ml). Intraoperative neuromonitoring was used in all the cases (5 mA). Translaryngeal ultrasound (TLUS) or direct laryngoscopy were routinely used prior and after surgery to evaluate vocal cords mobility. Calcium and parathormone levels were measured in patients after thyroidectomy on the first, 14th and 30th postoperative days. No recurrent laryngeal nerve palsy was observed. One patient exhibited hypoparathyroidism which was resolved in 2 weeks using substitution therapy with calcium and alfacalcidol. The mean operating time for lobectomy was 54 ± 14 min (range: 30-95 min) and for total thyroidectomy 99 ± 28 min (range: 55-158 min). There was no conversion to the conventional lateral-to-medial approach. TFT can be considered a safe and feasible operation. Comparative (randomized studies) with conventional dissection technique should be performed to investigate the hypothesis that this approach can provide a lower complication rate.

Clinical phenotypes of primary hyperparathyroidism in hospitalized patients who underwent parathyroidectomy.

OBJECTIVE: The aim of our study was to investigate the distribution of the PHPT clinical manifestations and biochemical features in patients who underwent parathyroidectomy. MATERIALS AND METHODS: Medical records of 449 patients from three Medical Centers (Saint-Petersburg, Russia), hospitalized during a period from 2011 to 2018, were reviewed. History and anthropometric data, laboratory results (iPTH, total and iCa, phosphorus, ALP, 24-h urinary calcium, 25(OH)D) and imaging data (ultrasonography, scintigraphy, CT/MRI scan, DXA) were analyzed. RESULTS: Three hundred ninety-four patients were included in the final analysis. Median age was 60 years with 94.2% being women. Symptomatic disease was evident in 222 (56.4%) patients, asymptomatic in 172 (43.6%). Skeletal involvement was more common for women, while frequency of other manifestations did not differ in both genders. There was no difference between symptomatic and asymptomatic patients in age. Serum iPTH level was higher in symptomatic patients (202.9 and 181.0 pg/mL, P = 0.022). Serum 25(OH)D level was estimated in few patients and negatively correlated with PTH (r = ¯0.294, P = 0.005), iCa (r = ¯0.268, P = 0.010) and total Ca (r = ¯0.284, P = 0.014) levels. Manifestations of CVD were observed in 67.7% of cases and affected equally both symptomatic and asymptomatic patients (70.7 and 63.4%, P = 0.076). Both age and BMI were higher in patients with CVD, whether or not they were symptomatic (62 and 53 years, P < 0.0001; 30.4 vs 26.0 kg/m2, P < 0.0001, respectively). CONCLUSIONS: This experience illustrates that symptomatic phenotype is still the most common form of PHPT.

Preoperative Typing of Thyroid and Parathyroid Tumors with a Combined Molecular Classifier.

In previous studies, we described a method for detecting and typing malignant tumors of the thyroid gland in fine-needle aspiration biopsy samples via analysis of a molecular marker panel (normalized HMGA2 mRNA level; normalized microRNA-146b, -221, and -375 levels; mitochondrial-to-nuclear DNA ratio; and BRAFV600E mutation) in cytological preparations by quantitative PCR. In the present study, we aimed to estimate the specificity of the typing of different thyroid tumors by the proposed method. Fine-needle aspiration cytological preparations from 278 patients were used. The histological diagnosis was known for each sample. The positive and negative predictive values of the method assessed in this study were, respectively, 100% and 98% for papillary thyroid carcinoma (n = 63), 100% and 100% for medullary thyroid carcinoma (n = 19), 43.5% and 98% for follicular carcinoma (n = 15), and 86% and 100% for Hürthle cell carcinoma (n = 6). Thus, we demonstrate that the diagnostic panel, including the analysis of microRNA expression, mRNA expression, the BRAFV600E mutation, and the mitochondrial-to-nuclear DNA ratio, allows the highly accurate identification of papillary thyroid carcinoma, medullary thyroid carcinoma, and Hürthle cell carcinoma but not malignant follicular tumors (positive predictive value was below 50%).

MiRNA let-7 from TPO(+) Extracellular Vesicles is a Potential Marker for a Differential Diagnosis of Follicular Thyroid Nodules.

BACKGROUND: The current approaches to distinguish follicular adenomas (FA) and follicular thyroid cancer (FTC) at the pre-operative stage have low predictive value. Liquid biopsy-based analysis of circulating extracellular vesicles (EVs) presents a promising diagnostic method. However, the extreme heterogeneity of plasma EV population hampers the development of new diagnostic tests. We hypothesize that the isolation of EVs with thyroid-specific surface molecules followed by miRNA analysis, may have improved diagnostic potency. METHODS: The total population of EVs was isolated from the plasma of patients with FA (n = 30) and FTC (n = 30). Thyroid peroxidase (TPO)-positive EVs were isolated from the total populations using immune-beads. The miRNA from the TPO(+)EVs obtained from the plasma of FA and FTC patients was assayed by RT-PCR. The diagnostic potency of the selected miRNAs was estimated by the receiver operating characteristic (ROC) analysis. RESULTS: TPO(+)EVs can be efficiently isolated by immunobeads. The analysis of Let-7 family members in TPO(+)EVs allows one to distinguish FA and FTC with high accuracy (area under curve defined by ROC = 0.77-0.84). CONCLUSION: The isolation of TPO(+)EVs, followed by RT-qPCR analysis of Let-7 family members, may present a helpful approach to manage follicular nodules in the thyroid gland.

Transcutaneous laryngeal ultrasonography (TLUS) as an alternative to direct flexible laryngoscopy (DFL) in the perioperative evaluation of the vocal cord mobility in thyroid surgery.

PURPOSE: Direct flexible laryngoscopy (DFL) is the golden standard to evaluate the vocal cord (VC) function in thyroid and parathyroid surgery pre- and postoperatively. Transcutaneous laryngeal ultrasonography (TLUS) could represent an alternative to the DFL and has been evaluated in the present study comparing the results of both methods performed at two referral centers for endocrine pathologies. METHODS: In the setting of a retrospective study, 668 patients (560 female, 118 male; mean age 50.3 ± 14.2) were included from two tertiary referral centers of endocrine surgery. In all patients, TLUS was performed pre- and postoperatively prior to transnasal DFL, which served as a golden standard. TLUS was performed by B-scan (probe 5-13 MHz, aperture 40 mm). RESULTS: Preoperative visualization of the vocal cords by TLUS was possible in 526 patients (78.7%). Due to the frequent thyroid cartilage calcification (TCC) in male patients, a significant difference in the visualization rate was found between female and male (88.7% vs. 26.8%) [p < 0.0001]. Additionally, the visualization rate was inversely related to the patient's age [p < 0.001]. The sensitivity of preoperative TLUS was found to be 66.7%, the specificity 100%. DFL confirmed a postoperative palsy in 34 out of 40 patients with supposed abnormal vocal cord mobility at TLUS and demonstrated a palsy in four more cases with supposed regular mobility at TLUS. Therefore, the sensitivity of postoperative TLUS was 86%, the specificity of 99.1%, positive predictive value 89.4%, negative predictive value 98.7%. CONCLUSIONS: TLUS could represent an alternative for the evaluation of vocal cords mobility. This method has the potential to replace the DFL in the majority of cases, especially in female patients. Nevertheless, DFL is still necessary in about 20% of the patients with failed visualization at TLUS.