Preoperative Diagnosis Of Thyroid Cancer Research Articles

Targeting DUSP5 suppresses malignant phenotypes of BRAF-mutant thyroid cancer cells and improves their response to sorafenib.

The role of dual-specificity phosphatase-5 (DUSP5) in BRAF-mutant thyroid cancers remains unclear. The aims of this study are to investigate the role of DUSP5 in BRAF-mutant thyroid cancer cells, explore its value in the diagnosis and evaluate therapeutic potential of targeting DUSP5 combined with sorafenib for BRAF-mutant thyroid cancer patients. The role of DUSP5 in thyroid cancer cells was determined by a series of in vitro and in vivo experiments. Underlying mechanisms were explored by western blotting analysis. The diagnostic value of combination detection of DUSP5 expression and BRAFV600E mutation was evaluated using ROC curve. Knocking down DUSP5 in BRAF-mutant thyroid cancer cells significantly inhibited colony formation, cell migration and invasion, meanwhile, induced cell cycle arrest and cell apoptosis. Moreover, inhibition of DUSP5 improved the anti-tumor efficacy of sorafenib both in vitro and in vivo. Besides, combination detection of DUSP5 expression and BRAFV600E mutation showed much more accuracy in preoperative diagnosis of thyroid cancer. Our data demonstrate an oncogenic role of DUSP5 in BRAF-mutant thyroid cancer cells, and combined analysis of its expression and BRAFV600E mutation can accurately diagnose thyroid cancer. In addition, inhibition of DUSP5 improves the response of BRAF-mutant thyroid cancer cells to sorafenib.

Nanomaterials: a promising multimodal theranostics platform for thyroid cancer.

Thyroid cancer is the most prevalent malignant neoplasm of the cervical region and endocrine system, characterized by a discernible upward trend in incidence over recent years. Ultrasound-guided fine needle aspiration is the current standard for preoperative diagnosis of thyroid cancer, albeit with limitations and a certain degree of false-negative outcomes. Although differentiated thyroid carcinoma generally exhibits a favorable prognosis, dedifferentiation is associated with an unfavorable clinical course. Anaplastic thyroid cancer, characterized by high malignancy and aggressiveness, remains an unmet clinical need with no effective treatments available. The emergence of nanomedicine has opened new avenues for cancer theranostics. The unique features of nanomaterials, including multifunctionality, modifiability, and various detection modes, enable non-invasive and convenient thyroid cancer diagnosis through multimodal imaging. For thyroid cancer treatment, nanomaterial-based photothermal therapy or photodynamic therapy, combined with chemotherapy, radiotherapy, or gene therapy, holds promise in reducing invasiveness and prolonging patient survival or alleviating pain in individuals with anaplastic thyroid carcinoma. Furthermore, nanomaterials enable simultaneous diagnosis and treatment of thyroid cancer. This review aims to provide a comprehensive survey of the latest developments in nanomaterials for thyroid cancer diagnosis and treatment and encourage further research in developing innovative and effective theranostic approaches for thyroid cancer.

Risk of Permanent Hypoparathyroidism Requiring Calcitriol Therapy in a Population-Based Cohort of Adults Older Than 65 Undergoing Total Thyroidectomy for Graves' Disease.

Objective: Total thyroidectomy for Graves' disease (GD) is associated with rapid treatment of hyperthyroidism and low recurrence rates. However, it carries the risk of surgical complications including permanent hypoparathyroidism, which contributes to long-term impaired quality of life. The objective of this study was to determine the incidence of permanent hypoparathyroidism requiring calcitriol therapy among a population-based cohort of older adults undergoing total thyroidectomy for GD in the United States. Methods: We performed a population-based cohort study using 100% Medicare claims from beneficiaries older than 65 years with GD who underwent total thyroidectomy from 2007 to 2017. We required continuous enrollment in Medicare Parts A, B, and D for 12 months before and after surgery to ensure access to comprehensive claims data. Patients were excluded if they had a preoperative diagnosis of thyroid cancer or were on long-term preoperative calcitriol. Our primary outcome was permanent hypoparathyroidism, which was identified based on persistent use of calcitriol between 6 and 12 months following thyroidectomy. We used multivariable logistic regression to identify characteristics associated with permanent hypoparathyroidism, including patient age, sex, race/ethnicity, neighborhood disadvantage, Charlson-Deyo Comorbidity Index, urban or rural residence, and frailty. Results: We identified 4650 patients who underwent total thyroidectomy for GD during the study period and met the inclusion criteria (mean age = 72.8 years [standard deviation = 5.5], 86% female, and 79% white). Among this surgical cohort, 104 (2.2% [95% confidence interval, CI = 1.8-2.7%]) patients developed permanent hypoparathyroidism requiring calcitriol therapy. Patients who developed permanent hypoparathyroidism were on average older (mean age 74.1 vs. 72.8 years) than those who did not develop permanent hypoparathyroidism (p = 0.04). On multivariable regression, older age was the only patient characteristic associated with permanent hypoparathyroidism (odds ratio age ≥76 years = 1.68 [CI = 1.13-2.51] compared with age 66-75 years). Conclusions: The risk of permanent hypoparathyroidism requiring calcitriol therapy among this national, U.S. population-based cohort of older adults with GD treated with total thyroidectomy was low, even when considering operations performed by a heterogeneous group of surgeons. These findings suggest that the risk of hypoparathyroidism should not be a deterrent to operative management for GD in older adults who are appropriate surgical candidates.

Improving the diagnosis of thyroid cancer by machine learning and clinical data

Thyroid cancer is a common endocrine carcinoma that occurs in the thyroid gland. Much effort has been invested in improving its diagnosis, and thyroidectomy remains the primary treatment method. A successful operation without unnecessary side injuries relies on an accurate preoperative diagnosis. Current human assessment of thyroid nodule malignancy is prone to errors and may not guarantee an accurate preoperative diagnosis. This study proposed a machine learning framework to predict thyroid nodule malignancy based on our collected novel clinical dataset. The ten-fold cross-validation, bootstrap analysis, and permutation predictor importance were applied to estimate and interpret the model performance under uncertainty. The comparison between model prediction and expert assessment shows the advantage of our framework over human judgment in predicting thyroid nodule malignancy. Our method is accurate, interpretable, and thus useable as additional evidence in the preoperative diagnosis of thyroid cancer.

Diagnostic approach to thyroid cancer based on amino acid metabolomics in saliva by ultra-performance liquid chromatography with high resolution mass spectrometry

Thyroid cancer is a malignant disease with dramatically low advanced-stage 10-year survival. Meanwhile, the metabolites in saliva are becoming a wealthy source of disease biomarkers. However, there is a lack of non-invasive analytical methods for the identification of biomarkers in saliva for the preoperative diagnosis of thyroid cancer. Therefore, we developed an ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) method to simultaneously determine the metabolic levels of 10 amino acids in saliva, aiming to study the amino acid metabolism profile to promote early diagnosis of thyroid cancer. We tested unstimulated whole saliva from patients with papillary thyroid carcinoma (PTC; n = 61) and healthy controls (HC; n = 61), and used receiver operating characteristic (ROC) curves to establish the diagnostic value of potential markers. The method validation results showed good precision, linearity (R2 > 0.99), recovery (92.2 %–110.3 %), intra- and inter-day precision (RSD < 7 % and RSD < 9 %, respectively). The concentration of 10 amino acids was significantly different between PTC and HC in human salivary analysis (P < 0.05), the area under the curve (AUC) values of a single marker for the diagnosis of PTC were ranging from 0.678 to 0.833. A panel of alanine, valine, proline, phenylalanine was selected in combination yielded the AUC of 0.936, which will improve the accuracy of early diagnosis of thyroid cancer (sensitivity: 91.2 %; specificity: 85.2 %). This study proved the possibility of salivary amino acid biomarkers for PTC early diagnosis, providing a simple auxiliary way for the non-invasive diagnosis of thyroid cancer.

Malignancy Analyses of Thyroid Nodules in Patients Subjected to Surgery with Cytological- and Ultrasound-Based Risk Stratification Systems

The fine needle aspiration (FNA) cytology is the gold standard for the preoperative diagnosis of thyroid cancer. However, up to 30% of FNA examinations yield nondiagnostic or indeterminate results and this complicates patient management. Clinical features and ultrasound (US) patterns, including US risk stratification systems, could be useful in the preoperative diagnostic workup and prediction of malignancy, but the evidences are not univocal. Methods: 400 consecutive patients subjected to thyroid surgery were retrospectively enrolled at our institution in Calabria, Southern Italy. Preoperative US and FNA cytological descriptions, formulated according to the “Italian consensus for reporting thyroid fine-needle aspiration cytology” (ICCRTC) classification and three US risk stratification systems (those developed by the American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi (AACE/ACE/AME), American Thyroid Association (ATA), and American College of Radiology (ACR-TIRADS)), were collected, along with histological results. Results: 147 thyroid cancer cases, in large majority papillary carcinomas, were detected on final histological examination. Almost two-thirds of patients subjected to thyroid surgery for either benign or malignant lesions were female. Patient’s age ≤20 years and between 21–30 years were clinical features associated with increased risk of thyroid cancer in logistic regression analyses. US features associated with thyroid cancer included irregular margins, solid composition, microcalcifications, and marked hypoechogenicity. The AACE/ACE/AME, ATA, and ACR-TIRADS risk categories, corresponding to specific US patterns, were strong predictors of malignancy in both genders, but not in nodules with indeterminate cytology. A measured difference between the longitudinal (L) and the anteroposterior (AP) diameter &gt;5 mm, a proxy for a parallel-oriented oval shape of a nodule, emerged as a robust protective factor against thyroid cancer (OR 0.288 (95%CI 0.817–0.443); p &lt; 0.001), regardless of cytological risk. Conclusions: Some, but not all, well-established predictors of TC have been confirmed in this study. Controversy surrounds the diagnostic performance of US risk stratification systems for the detection of thyroid cancer in the subgroup of nodules with indeterminate cytology, suggesting their use only to set the thresholds for FNA. A measured difference between L and AP diameters &gt;5 mm may represent an additional and practical tool for ruling out malignancy in thyroid nodules, with the potential to reduce unnecessary surgical procedures.

BRAF status in сito-morphological diagnosis of thyroid nodules

The aim of study – to determine the significance of the BRAF V600E mutation presence in the cytomorphological diagnosis of thyroid nodules.Materials and methods. The study included 65 patients requiring surgical treatment for thyroid nodular pathology. Material to determine the BRAF V600E mutation was taken by means of a fine needle aspiration biopsy before surgery. The BRAF V600E mutation was detected by real-time PCR analysis.Results. A pathomorphological study of the removed thyroid nodules showed that all 22 benign nodules were BRAF-negative. Among the 43 papillary thyroid cancer only 20 were BRAF-positive (46.5 %). BRAF mutations were found more often (P < 0.001) in patients with classical and oxyphilic cell papillary thyroid cancer (60 % and 100 %, respectively) than in patients with follicular variant of PTC (6.7 %). Locally invasive tumors were more often BRAF-negative cases (P < 0.05) than non-invasive tumors and amounted to 75.0 % and 37.5 %, respectively. But, when comparing the morphological variant and invasive properties of the tumor, it was found that all cases of the follicular variant of the PC had signs of invasion and were significantly more often observed (P < 0.01) compared with the classical and oxyphilic cell variants. The BRAF V600E mutation was observed both in tumors with metastasis to the regional lymph nodes (55.0 %) and in tumors without metastases (37.5 %), with no significant difference.Conclusions. The presence of the BRAF V600E mutation is a diagnostic marker for papillary thyroid carcinoma, and its detection confirms the presence of malignancy. BRAF positive carcinomas were in 46.5 % of cases. The combination of BRAF-negative and the cytology of groups V and VI by Bethesda may indicate about a follicular variant of PTC. An increase in the number of molecular genetic markers in the preoperative diagnosis of thyroid cancer can significantly improve the quality of diagnosis and surgical treatment.

Thyroid cancer: retrospective study of patients with surgical treatment (a single-center experience)

Introduction. Nodular goiter is one of the most common endocrine disorder, and thyroid cancer takes a leading place among malignancy of the endocrine system. The aim of our study is to evaluate the prevalence and risk factors of thyroid cancer. Materials and methods: this is a retrospective case-control study that included 140 patients operated with suspected thyroid cancer according to a cytological study of fine needle aspirates in single center in 2018. All patients underwent preoperative cytological examination with interpretation of the results according to the Bethesda system, thyroid ultrasound examination, thyroid status assessment. The results of the cytological examination, as well as clinical and laboratory data were compared with the data of histological analysis. Results: According to the preoperative cytological study, 76 nodules were reported as Bethesda IV, 4 – Bethesda III, 32 – Bethesda VI, 28 – Bethesda V. According to the results of a histological examination, thyroid cancer was confirmed in 70% of patients: in 89,3% of Bethesda V and 100% in the Bethesda VI group, 52,6% of Bethesda IV, 25% of the Bethesda III. The risk of nodule malignancy was associated with such ultrasound signs as hypoechoicity, calcifications and irregular contours. Conclusions: the improvement of the methods of preoperative diagnosis of thyroid cancer should help to choose the optimal surgical strategy, reduce the number of diagnostic and repeated thyroidectomy.

Interconnection between circadian clocks and thyroid function.

Circadian rhythmicity is an approximately 24-h cell-autonomous period driven by transcription-translation feedback loops of specific genes, which are referred to as 'circadian clock genes'. In mammals, the central circadian pacemaker, which is located in the hypothalamic suprachiasmatic nucleus, controls peripheral circadian clocks. The circadian system regulates virtually all physiological processes, which are further modulated by changes in the external environment, such as light exposure and the timing of food intake. Chronic circadian disruption caused by shift work, travel across time zones or irregular sleep-wake cycles has long-term consequences for our health and is an important lifestyle factor that contributes to the risk of obesity, type 2 diabetes mellitus and cancer. Although the hypothalamic-pituitary-thyroid axis isunder the control of the circadian clock via the suprachiasmatic nucleus pacemaker, daily TSH secretion profiles are disrupted in some patients with hypothyroidism and hyperthyroidism. Disruption of circadian rhythms has been recognized as a perturbation of the endocrine system and of cell cycle progression. Expression profiles of circadian clock genes are abnormal in well-differentiated thyroid cancer but not in the benign nodules or a healthy thyroid. Therefore, the characterization of the thyroid clock machinery might improve the preoperative diagnosis of thyroid cancer.

HMGA2 Gene Expression in Fine-needle Aspiration Samples of Thyroid Nodules as a Marker for Preoperative Diagnosis of Thyroid Cancer.

There is a great interest in molecular markers that would help in the preoperative diagnosis of malignant thyroid nodules in cases of indeterminate fine-needle aspiration cytology. The aim of this study was to determine the diagnostic accuracy of HMGA2 gene expression in discriminating benign from malignant thyroid nodules. In this study, 237 preoperative thyroid fine-needle aspiration samples were analyzed prospectively for the expression of the HMGA2 gene by real-time reverse transcription polymerase chain reaction. The results were evaluated against the postoperative histopathologic diagnosis or definitive cytologic diagnosis in cases of nodular goiter and Hashimoto thyroiditis. Among 237 samples from patients with thyroid nodules that were analyzed, 231 were adequate for real-time reverse transcription polymerase chain reaction analysis. With a cutoff value of 8.71 for relative gene expression, HMGA2 was positive in 19 (16.4%) of 116 nodular goiter, 1 (2.6%) of 39 Hashimoto thyroiditis, 9 (28.1%) of 32 follicular adenoma, 0 (0%) of 5 Hurthle cell adenoma, 32 (88.9%) of 36 papillary carcinoma, and 3 (100%) of 3 follicular carcinoma samples. In discriminating between malignant and benign thyroid nodules, HMGA2 has shown specificity of 84.5%, sensitivity of 91.9%, positive predictive value of 53.1%, and negative predictive value of 98.2%. High sensitivity and negative predictive value of HMGA2 for preoperative detection of malignant thyroid nodules shown in this study indicate that it may have a role as an ancillary marker in cytology in the management of patients with thyroid nodules.

Accuracy of ultrasonography-guided fine needle aspiration cytology and significance of non-diagnostic cytology in the preoperative detection of thyroid malignancy.

Thyroid fine-needle aspiration cytology (FNAC) is an established investigation for the preoperative evaluation of thyroid nodules and is often done under ultrasonography guidance. While its accuracy has been widely reported, there is little evidence in the literature on the approach to non-diagnostic cytology results. In our study, we aimed to determine the diagnostic performance of ultrasonography-guided thyroid FNAC for the preoperative diagnosis of thyroid cancer at our institution and evaluate the significance of a non-diagnostic thyroid FNAC. We retrospectively reviewed the thyroid ultrasonography studies and medical records of all patients who underwent both thyroid FNAC and subsequent thyroid surgery at our institution from 2011 to 2013. FNAC results were correlated with the final histological diagnosis from surgery and the ultrasonography studies were reviewed for suspicious sonographic features. FNAC predicted malignancy with sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, false negative rate and total accuracy of 90.7%, 53.6%, 43.3%, 93.7%, 46.4%, 9.3% and 64.1%, respectively. We found that only one of 26 nodules with non-diagnostic FNAC results was proven malignant on a second FNAC and subsequent thyroidectomy. The accuracy of ultrasonography-guided FNAC at our institution was comparable to that reported in the literature. There appears to be very low probability of malignancy in sonographically benign nodules with initial non-diagnostic FNAC results.

Ultra-Low-Dose Neck CT With Low-Dose Contrast Material for Preoperative Staging of Thyroid Cancer: Image Quality and Diagnostic Performance.

Although CT has been used as a complementary diagnostic method for the preoperative diagnosis of thyroid cancer, it has the shortcomings of substantial radiation exposure and the use of contrast material (CM). The purpose of this article is to evaluate the image quality and diagnostic performance of 70-kVp thyroid CT with low volumes of CM versus conventional 120-kVp thyroid CT protocol. Eighty patients referred for preoperative thyroid CT were randomly divided into two groups (group A: 40 patients, 70 kVp, 60 mL of CM; group B: 40 patients, 120 kVp, 100 mL of CM). Quantitative and qualitative image quality and radiation doses for the two groups were compared using the Mann-Whitney U and chi-square tests. Degrees of agreement between preoperative CT staging and pathologic results were evaluated and compared using the Wald statistic. Calculated signal-to-noise ratios of different anatomic structures, calculated contrast-to-noise ratios, overall image quality, subjective noise, and streak artifacts were not significantly different between the two groups (all p > 0.05), and neither were the accuracies of preoperative CT staging (all p > 0.05). The estimated effective doses were significantly lower in group A (mean [± SD], 0.52 ± 0.14 mSv in group A and 2.28 ± 0.29 mSv in group B; p < 0.001). Ultra-low-dose 70-kVp CT with a low volume of CM provides sufficient image quality for preoperative staging of thyroid cancer and substantially reduces the radiation dose compared with standard 120-kVp CT.

Raman spectroscopy for the preoperative diagnosis of thyroid cancer and its subtypes: An in vitro proof‐of‐concept study

In 2016, there were an estimated 56870 new cases of thyroid cancer (TC) in the USA. Fine needle aspiration cytology (FNAC) is the most safe, accurate and cost-effective method for the initial investigation of thyroid nodules. FNAC is limited by the inability to diagnose malignancy in follicular-patterned lesions accurately and, as a result, 20%-30% of cases under investigation for TC are classified as cytologically indeterminate, illustrating a problem with current FNAC procedure. Raman spectroscopy has shown promising results for the detection of many cancers; however, to date there has been no report on the performance of Raman spectroscopy on thyroid cytological samples. The aim of this study was to examine whether Raman spectroscopy could be used to correctly classify cell lines representing benign thyroid cells and various subtypes of TC. A benign thyroid cell line and seven TC cell lines were prepared as ThinPrep® cytology slides and analysed with Raman spectroscopy. Principal components analysis and linear discriminant analysis were implemented to develop effective diagnostic algorithms for classification of Raman spectra of different TC subtypes. The spectral differences separating benign and TC cell lines were assigned to differences in the composition of nucleic acids, lipids, carbohydrates and protein in the benign and cancer cells. Good sensitivities (74%-85%), specificities (65%-93%) and diagnostic accuracies (71%-88%) were achieved for the identification of TC. These findings suggest that Raman spectroscopy has potential for preoperative TC diagnosis on FNAC samples.

ANALYSIS OF RELATIVE EXPRESSION OF THE HMGA2 GENE AND ONCOGENIC MICRORNA-221 IN CYTOLOGICAL SLIDES OBTAINED BY A FINE-NEEDLE ASPIRATION BIOPSY OF THE THYROID NODULES

Background. Fine-needle aspiration biopsy is recognized as the “gold standard” in the preoperative diagnosis of thyroid cancer. However, this method does not always allow reliable differentiation between benign and malignant thyroid nodules. Thus, the cytological report of a “follicular neoplasm or suspicious for a follicular neoplasm” suggests surgical lobectomy. However, in most cases, this conclusion does not point to follicular cancer but to benign neoplasm, follicular adenoma, where the surgical intervention is excessive. This implies the great relevance of finding biological markers capable of enhancing the specificity of detecting malignant neoplasms. Such markers may include an increase in the level of expression of oncogenes or a change in the expression of microRNA, since it is known that the content of a number of microRNAs changes significantly during the development of thyroid tumors. Materials and methods. The expression level of the HMGA2 gene, normally active at the embryonic stage, and oncogenic miRNA-221 microRNA was analyzed using real-time reverse transcription polymerase chain reaction in 713 cytological preparations of the thyroid gland (stained material dried on glasses) obtained by standard fine-needle aspiration biopsy. The sample included preparations corresponding to different cytological diagnoses: benign (n = 375), follicular neoplasm or suspicious for a follicular neoplasm (n = 143), medullary carcinoma (n = 7), papillary carcinoma (n = 186) and anaplastic carcinoma (n = 2). Results. The content of messenger RNA (mRNA) HMGA2 (P = 1.6 × 10–66, area under curve ROC 0.946) and miR-221 (P = 6.3 × 10 –61 , area under curve ROC 0.927) proved to be significantly elevated in papillary carcinoma compared to benign tumors. Follicular neoplasms showed significant heterogeneity in the quantity of both molecular markers. At the same time, an elevated level of miR-221 (3 times on average) was also characteristic of samples from this group with an increased level of expression of the HMGA2 gene (an average of 85 times). With regard to the quantity of these markers, the group of follicular neoplasms, in which no increase in the HMGA2 mRNA level was detected, did not differ from the group of benign nodules. Conclusions. The obtained results show that assessing the expression of HMGA2 mRNA and oncogenic miR-221 makes it possible to differentiate the papillary thyroid carcinoma from goiter at the preoperative stage, and based on the content of the HMGA2 mRNA, the group of follicular neoplasms can be divided into subgroups presumably differing in the risk of malignancy.

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma.

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers. We conducted a retrospective review of 713 consecutive patients who underwent thyroidectomies. Incidental thyroid cancer was defined as an unexpected cancer discovered on pathological examination outside the index nodule undergoing preoperative cytology. We excluded 65 cases because of preoperative diagnosis of thyroid cancer, and 68 because of nonincidental cancer within the index nodule. Among the remaining 580 cases, there were 43 cases (7.4%) of incidental thyroid cancers. Incidental thyroid cancers were significantly associated with moderate/severe lymphocytic thyroiditis (relative risk = 2.5; p = .03). Sixteen of 56 patients with moderate/severe lymphocytic thyroiditis had Graves' disease, none of whom had incidental thyroid cancer. The risk of incidental thyroid cancer associated with moderate/severe lymphocytic thyroiditis was significantly higher in non-Graves' than patients with Graves' disease (p = .05). The risk of incidental thyroid cancer is significantly increased in patients with moderate/severe lymphocytic thyroiditis. Moderate/severe lymphocytic thyroiditis associated with Graves' disease seems to have a lower risk of incidental thyroid cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 122-127, 2017.

Metabolomic analysis of percutaneous fine-needle aspiration specimens of thyroid nodules: Potential application for the preoperative diagnosis of thyroid cancer.

Thyroid nodules are a very common problem. Since malignant thyroid nodules should be treated surgically, preoperative diagnosis of thyroid cancer is very crucial. Cytopathologic analysis of percutaneous fine-needle aspiration (FNA) specimens is the current gold standard for diagnosing thyroid nodules. However, this method has led to high rates of inconclusive results. Metabolomics has emerged as a useful tool in medical fields and shown great potential in diagnosing various cancers. Here, we evaluated the potential of nuclear magnetic resonance (NMR) analysis of percutaneous FNA specimens for preoperative diagnosis of thyroid cancer. We analyzed metabolome of FNA samples of papillary thyroid carcinoma (n = 35) and benign follicular nodule (n = 69) using a proton NMR spectrometer. The metabolomic profiles showed a considerable discrimination between benign and malignant nodules. Receiver operating characteristic (ROC) curve analysis indicated that seven metabolites could serve as discriminators (area under ROC curve value, 0.64–0.85). These findings demonstrated that NMR analysis of percutaneous FNA specimens of thyroid nodules can be potentially useful in the accurate and rapid preoperative diagnosis of thyroid cancer.

Possibilities traditional and liquid-based cytology combined with immunocytochemical detection of some molecular markers in the preoperative diagnosis of well-differentiated thyroid cancer

Aim . To establish the diagnostic value of liquid and traditional cytological diagnosis with immunocytochemical (ICC) detection proteins (galectin-3, nucleophosmin, Ki-67) in the preoperative diagnosis of well-differentiated thyroid cancer and analysis of the effect of the autoimmune process in the thyroid gland in the diagnostic accuracy. Materials and methods . The traditional liquid-based cytology was performed on 107 samples and immunocytochemistry performed on 56 samples with histological findings: colloid goiter in 24 cases, 4 cases of Hashimoto’s thyroiditis, 4 cases of follicular adenoma, 22 cases of papillary cancer. Results . The results of a comparison of cytological and histological findings. The results of studies of diagnostic accuracy expression of galectin-3, nucleophosmin, Ki-67 for the diagnosis of thyroid cancer. A formula was developed to help determine the presence of malignancy in thyroid with high accuracy. Conclusion . The diagnostic accuracy of the method of liquid-based cytology is higher than the traditional method of cytology. ICC expression of Ki-67 method has 81.8% of sensitivity and 100% of specificity for the preoperative diagnosis of thyroid cancer. Conjoint definition HS Ki-67 and liquid-based cytology increases the sensitivity and specificity of the diagnosis of well-differentiated thyroid cancer preoperative to 100%. There no detected relations between the expression of galectin-3, NFM, Ki-67 and the presence an autoimmune process in the thyroid.

P82a: Molecular biomarkers in preoperative diagnosis of thyroid cancer

Preoperative differential diagnosis of benign thyroid nodules and thyroid cancer is an important issue of endocrinology. Preoperative identification of a tumor type allows a surgeon to determine an adequate surgical treatment and reduce complications. The cytological analysis of samples obtained by the fine-needle aspiration biopsy is limited in sensitivity and specificity and the core biopsy is not safe to be used in patients with thyroid nodes smaller than 2 cm. The most promising area in the preoperative diagnosis of malignant tumors is molecular biomarkers, which can be used to determine the surgical treatment and indications for the target therapy. BRAF V600E is the most frequent genetic alteration in thyroid cancer. It activates the MAP-kinase pathway which causes changes in expression levels of extracellular matrix proteins and some of their receptors. Changes in the expression of integrin receptors and their ligands, such as osteopontin and thrombospondin-1, contribute to tumor cell proliferation and migration. The C-Jun pathway is also very important in pathogenesis of thyroid cancer. Changes in its activity can affect the expression of GSTP enzyme which participates in hormone metabolism. Altered MiRNA expression has been observed in a variety of cancer states allowing their potential use as cancer biomarkers. The aim of this study was to evaluate integrins, angiogenic factors, GSTP and MiRNAs as potential biomarkers for the diagnosis and prognosis of thyroid cancer. 112 samples of papillary thyroid cancer (PTC) and 120 samples of benign nodular neoplasms were analyzed. The expression levels of the studied genes were determined by RT-PCR. The results were confirmed by immunohistochemical analysis. The BRAF V600E mutation was determined by allele-specific real-time PCR. The results showed that GSTP can be used for clinical settings as a cancer-specific marker for thyroid neoplasms with 83–88% sensitivity, 70–80% specificity and 76–84% diagnostic accuracy. Higher expression levels of integrins α 2, α 5, α v, α 9, β 1, β 3 and IL-8, angiogenin, and VEGF were observed in malignant tumors in comparison with the normal thyroid tissue ( p p

Factors affecting hypocalcaemia following total thyroidectomy: a prospective study.

After thyroidectomy hypocalcaemia is the most significant complication for clinicians. In this study, we investigated the factors associated with development of hypocalcaemia after thyroidectomy. We investigated the patients prospectively for age, gender, preoperative diagnosis, hormonal status, operative time, operating surgeon, existence of parathyroid gland injury at the operation, parathyroid gland auto-transplantation, preoperative use of anti-thyroid drugs and amount of bleeding at the operation. After operation in 1 and 2 days, serum calcium and phosphor, and in the 1 day parathyroid hormone values were evaluated. The chi-square test was applied in the analysis of categorical variables. Logistic regression model was used to determine the risk of hypocalcaemia in the univariate analysis. Hypocalcaemia developed in 47 of 196 patients. Female gender, preoperative diagnosis of thyroid cancer and toxic nodular goitre, <3cm nodule size, parathyroid injury and auto-transplantation and low vitamin D levels were factors found to be associated with hypocalcaemia in the Logistic regression analysis. The factors associated with hypocalcaemia were defined to be "gender, preoperative diagnosis, parathyroid gland injury, nodule size and vitamin D deficiency", it is a multifactorial problem and it would not be proper to define a few etiological factors.

Surgical therapy of thyroid cancer

The prevalence of thyroid cancer has shown an upward trend in China in recent years. Advances in thyroid ultrasound and fine needle puncture cytology have improved the accuracy of the preoperative diagnosis of thyroid cancer. Also,the application of endoscopy-assisted techniques and intraoperative nerve monitoring technology and the further understanding of thyroid lymph node metastasis have made the thyroid surgeries safer and less invasive. This article summarizes the recent advances in the surgical therapy of thyroid cancer.