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1.
Superior parathyroid blood supply safety in thyroid cancer surgery: A randomized controlled trial.
Kong, DD, Wang, W, Wang, MH
International journal of surgery (London, England). 2019;:33-39
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Abstract
BACKGROUND To evaluate the clinical value of a technique protecting blood supply to the superior parathyroid during surgery for thyroid cancer. MATERIALS AND METHODS The observation group comprised 113 patients admitted to our hospital during the period from January 1, 2016 to December 31, 2016, who were diagnosed with thyroid cancer and treated by surgery using a technique protecting blood supply to the superior parathyroid. The control group comprised 113 patients diagnosed with thyroid cancer who were treated by surgery using the conventional technique. Postoperative parathyroid function damage and blood calcium levels were assessed in both groups. RESULTS The incidences of hypocalcemia and low parathyroid hormone in the observation and control groups were 10.6% and 31.9%, and 14.2% and 35.4%, respectively. The relative risk (RR) of the control group was increased (RR = 3.009 for control; RR = 2.493 for observation). Univariate logistic regression analysis showed that postoperative temporary hypoparathyroidism was associated with lymph node metastasis, use of the above protective technique, and tumor size [(odds ratio, OR = 1.936, 95%CI 1.029-3.643; P = 0.041), (OR = 0.301, 95%CI 0.156-0.579; P = 0.001) and (OR = 2.022, 95%CI 1.089-3.756; P = 0.026), respectively]. Postoperative temporary hypoparathyroidism was also associated with lymph node dissection (Bilateral vs. No, P = 0.003) and T classification (T3 vs. T1, P = 0.034). Multivariate logistic regression analysis showed that, after including significant independent variables of univariate logistic regression analysis (e.g., lymph node metastasis, lymph node resection, protective technique, tumor size, and T classification), the protective technique was a factor supporting reduced incidence of postoperative temporary hypoparathyroidism (OR = 0.325, 95% CI 0.163-0.648; P = 0.001). CONCLUSION Application of a technique protecting blood supply to the superior parathyroid during thyroid cancer surgery effectively reduced the incidence of postoperative temporary hypoparathyroidism. However, because of the imbalance in lymph node dissection between the two groups, confounding factors could not be completely eliminated, and matched pair analysis is needed to eliminate these factors.
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Histone Deacetylase Inhibitors and Anaplastic Thyroid Carcinoma.
Spartalis, E, Athanasiadis, DI, Chrysikos, D, Spartalis, M, Boutzios, G, Schizas, D, Garmpis, N, Damaskos, C, Paschou, SA, Ioannidis, A, et al
Anticancer research. 2019;(3):1119-1127
Abstract
BACKGROUND/AIM: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, remaining generally incurable. Histone deacetylase (HDAC) seems to play a role in regulating transcription of genes involved in ATC, making HDAC inhibitors (HDACI) promising anticancer drugs for ATC. The purpose of this review was to evaluate the role of HDACIs in ATC treatment and describe the latest trends of current research on this field. MATERIALS AND METHODS This literature review was performed using the MEDLINE database. The keywords/phrases were; thyroid cancer, anaplastic, HDAC, histone, deacetylase*, HDACI. RESULTS Compounds, such as SuberoylAnilide Hydroxamic Acid, valproic acid, sodium butyrate, butyrate, phenylbutyrate, trichostatin A, AB1-13, panobinostat or LBH589, belinostat, MS-275, depsipeptide, CUDC101, CUDC907, N-Hydroxy-7-(2-naphthylthio)-Hepanomide (HNHA), and PXD101 have shown promising antitumor effects against ATC. CONCLUSION HDACIs represent a promising therapy for ATC management, both as monotherapy and in combination with other anticancer drugs.
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Urinary iodine is increased in papillary thyroid carcinoma but is not altered by regional population iodine intake status: a meta-analysis and implications.
Yan, AR, Zhang, X, Shen, H, Zhou, X, Li, R, Yuan, Z
Endocrine journal. 2019;(6):497-514
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Abstract
Excessive iodine intake has been associated with increased risk of thyroid cancer (TC) in many studies, but the results have not been consistent. Since it was common knowledge that urinary iodine (UI) is considered a sensitive marker of current iodine intake, we conducted a meta-analysis to clarify the association between high UI and TC. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the Cochrane Collaboration. Between-group meta-analyses were performed to compare UI between TC patients and the healthy/euthyroid subjects in local residents and benign thyroid nodules (BTN) patients. Then, between-group meta-analyses to compare the incidence rate of iodine excess were also conducted. The 22 case-control studies included in the meta-analyses represented 15,476 participants. It is the first time to clarify that UI was increased in PTC patients, but was not altered by regional population iodine intake status. Compared with BTN patients, PTC patients exhibited both higher UIC and higher odds ratio of iodine excess only in adequate iodine intake status subgroup; UIC, not the odds ratio of iodine excess, was higher in patients with PTC than those with BTN in above requirements iodine intake subgroup. A novel insight is offered that high UI in PTC patients was less influenced by regional population iodine intake status. It is indicted that high iodine intake is not a risk factor for PTC and high urinary iodine is just a specific characteristic of the disease.
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124I Positron Emission Tomography/Computed Tomography Versus Conventional Radioiodine Imaging in Differentiated Thyroid Cancer: A Review.
Wu, D, Ylli, D, Heimlich, SL, Burman, KD, Wartofsky, L, Van Nostrand, D
Thyroid : official journal of the American Thyroid Association. 2019;(11):1523-1535
Abstract
Background: Studies report a wide spectrum of 124I positron emission tomography (PET)/computed tomography (CT) sensitivity and specificity in the detection of differentiated thyroid cancer (DTC) lesions. This study reviews the lesion detection rate of pretherapy 124I PET/CT in different patient populations and further analyzes the factors necessary for a better detection on 124I PET/CT. Methods: A literature search was performed using multiple different databases (MEDLINE, EMBASE, Northern Lights, and handsearching) covering 1996 to April 2018. Two reviewers reviewed and extracted study data for 124I, 123I, and 131I scans in DTC. Results: This review includes 4 retrospective and 10 prospective studies in which 495 DTC patients underwent 124I and 131I imaging; no studies made comparisons with 123I. In the reports that compared 124I PET/CT with diagnostic 131I scans, there were a total of 72 patients in whom 120 lesions were detected on 124I imaging, whereas only 52 were detected on diagnostic 131I scans. In publications that compared 124I with post-therapy 131I scans in 266 patients, 410 lesions were detected with 124I PET, whereas 390 were detected on post-therapy 131I scans. Based on 124I PET/CT in six studies, TNM staging was revised in 15-21% of patients, and disease management was altered in 5-29% of patients. Conclusions:124I PET/CT is able to identify a greater number of foci compared with diagnostic 131I scans. 124I PET may have better detection compared with post-therapy 131I scans in patients who are 131I therapy naive, have less aggressive pathology, or do not have disseminated lung metastases. Additional metastatic lesion detection by 124I PET may have a significant clinical impact in the management of patients before 131I therapy in some patients.
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Sunitinib in the Treatment of Thyroid Cancer.
Ferrari, SM, Centanni, M, Virili, C, Miccoli, M, Ferrari, P, Ruffilli, I, Ragusa, F, Antonelli, A, Fallahi, P
Current medicinal chemistry. 2019;(6):963-972
Abstract
BACKGROUND Sunitinib (SU11248) is an oral multi-target tyrosine kinase inhibitor (TKI) with low molecular weight, that inhibits platelet-derived growth factor receptors (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), c-KIT, fms-related tyrosine kinase 3 (FLT3) and RET. The concurrent inhibition of these pathways reduces tumor vascularization and causes cancer cell apoptosis, inducing a tumor shrinkage. Sunitinib is approved for the treatment of imatinib-resistant gastrointestinal stromal tumor (GIST), renal carcinoma, and pancreatic neuroendocrine tumors. METHODS We searched the literature on PubMed library. RESULTS In vitro studies showed that sunitinib targeted the cytosolic MEK/ERK and SAPK/JNK pathways in the RET/PTC1 cell inhibiting cell proliferation and causing stimulation of sodium/iodide symporter (NIS) gene expression in RET/PTC1 cells. Furthermore sunitinib is active in vitro and in vivo against anaplastic thyroid cancer (ATC) cells. Most of the clinical studies report that sunitinib is effective as first- and second-line TKI therapy in patients with advanced dedifferentiated thyroid cancer (DeTC), or medullary thyroid cancer (MTC). Sunitinib 37.5 mg/day is well tolerated, and effective. The most common adverse events include: reduction in blood cell counts (in particular leukocytes), hand-foot skin reaction, diarrhea, fatigue, nausea, hypertension, and musculoskeletal pain. CONCLUSION Even if sunitinib is promising in the therapy of differentiated thyroid carcinoma (DTC), until now no phase III studies have been published, and additional prospective researches are necessary in order to evaluate the real efficacy of sunitinib in aggressive thyroid cancer.
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Management of treatment-related toxicities in advanced medullary thyroid cancer.
Tsang, VHM
Current opinion in oncology. 2019;(3):236-242
Abstract
PURPOSE OF REVIEW Tyrosine kinase inhibitors (TKI), predominantly vandetanib and cabozantinib, are increasingly used for management of advanced medullary thyroid cancer. This review aims to discuss the major and serious adverse events associated with TKI. RECENT FINDINGS The choice of TKI depends on the patient's existing comorbidities. Patients who have long QT interval should avoid vandetanib and those at risk of gastrointestinal perforation should avoid cabozantinib. Hypertension is common during the first 3 months. Treatments include ACE inhibitors, calcium channel blockers (avoiding verapamil and diltiazem, which are CYP3A4 inhibitors), and beta blockers. Diuretics should be second line because of derangement of electrolytes, which may exacerbate QT interval. As nitric oxide (NO) blockade and ET1 are implicated in the mechanism of hypertension, nitrates and endothelin receptor antagonists may be used. Thromboembolism may require anticoagulation or revascularization procedures. Prolonged QT interval should be treated by dose interruption and reduction, correction of electrolytes, and avoidance of medications, which prolong QTc interval. Diarrhoea is managed symptomatically and with electrolyte replacement, dermatological adverse events with avoidance of exacerbating factors and topical therapies. Thyroid function should be monitored. SUMMARY Toxicities are common with TKI use, and management involves symptomatic treatment, avoidance of triggers, dose interruption, and dose reduction.
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Vitamin D deficiency as a risk factor for thyroid cancer: A meta-analysis of case-control studies.
Zhao, J, Wang, H, Zhang, Z, Zhou, X, Yao, J, Zhang, R, Liao, L, Dong, J
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:5-11
Abstract
OBJECTIVE The association between vitamin D deficiency and thyroid cancer is controversial. Some studies have demonstrated that higher serum vitamin D levels might protect against thyroid cancer, whereas others have not, or have even indicated the opposite to be the case. The aim of this meta-analysis was to investigate the association between vitamin D deficicency and thyroid cancer and propose that vitamin D deficiency is a risk factor for thyroid cancer. METHODS This was a meta-analysis of 14 articles of the association between vitamin D deficiency and thyroid cancer. Databases including PubMed, Cochrane library, Sinomed, CNKI, Wanfang, and clinical trial register centers, were searched for case-control studies of vitamin D in thyroid cancer. RESULTS Fourteen studies were included in this meta-analysis. A fixed-effect model was used to merge the standardized mean difference value of serum 25-hydroxyvitamin D levels. The pooled effect showed that the levels of serum 25-hydroxyvitamin D were lower in patients with thyroid cancer preoperatively than in the controls (-0.22; 95% confidence interval [CI], -0.36 to -0.09; P = 0.001). There was no difference after thyroid cancer patients underwent thyroidectomy (-0.19; 95% CI, -0.47 to 0.10; P = 0.21). A fixed-effect model was used to pool the odds ratio of thyroid cancer and vitamin D deficiency. It showed that the pooled odds ratio from six studies was 1.30 (95% CI, 1.00-1.69; P = 0.05). Subgroup analysis of 25-hydroxyvitamin D levels between different pathologic characteristics in patients with thyroid cancer was summarized, but no statistical differences were determined. CONCLUSIONS Lower serum 25-hydroxyvitamin D levels were associated with increased risk for thyroid cancer. On the other hand, vitamin D deficiency may act as a risk factor for thyroid cancer.
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Antiproliferative Effects of Cynaropicrin on Anaplastic Thyroid Cancer Cells.
Lepore, SM, Maggisano, V, Lombardo, GE, Maiuolo, J, Mollace, V, Bulotta, S, Russo, D, Celano, M
Endocrine, metabolic & immune disorders drug targets. 2019;(1):59-66
Abstract
BACKGROUND The sesquiterpene lactone cynaropicrin, a major constituent of the artichoke leaves extracts, has shown several biologic activities in many preclinical experimental models, including anti-proliferative effects. OBJECTIVE Herein we evaluated the effects of cynaropicrin on the growth of three human anaplastic thyroid carcinoma cell lines, investigating the molecular mechanism underlying its action. METHOD MTT assay was used to evaluate the viability of CAL-62, 8505C and SW1736 cells, and flow cytometry to analyse cell cycle distribution. Western blot was performed to detect the levels of STAT3 phosphorylation and NFkB activation. Antioxidant effects were analyzed by measuring the reactive oxygen species and malonyldialdehyde dosage was used to check the presence of lipid peroxidation. RESULTS Viability of CAL-62, 8505C and SW1736 cells was significantly reduced by cynaropicrin in a dose- and time-dependent way, with an EC50 of about 5 µM observed after 48 h of treatment with the compound. Cellular growth inhibition was accompanied both by an arrest of the cell cycle, mainly in the G2/M phase, and the presence of a significant percentage of necrotic cells. After 48 h of treatment with 10 µM of cynaropicrin, a reduced nuclear expression of NFkB and STAT3 phosphorylation were also revealed. Moreover, we observed an increase in lipid peroxidation, without any significant effect on the reactive oxygen species production. CONCLUSION These results demonstrate that cynaropicrin reduces the viability and promotes cytotoxic effects in anaplastic thyroid cancer cells associated with reduced NFkB expression, STAT3 phosphorylation and increased lipid peroxidation. Further characterization of the properties of this natural compound may open the way for using cynaropicrin as an adjuvant in the treatment of thyroid cancer.
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Conventional Radioiodine Therapy for Differentiated Thyroid Cancer.
Ylli, D, Van Nostrand, D, Wartofsky, L
Endocrinology and metabolism clinics of North America. 2019;(1):181-197
Abstract
This article presents an overview of the use of radioactive iodine (131-I) in the treatment of patients with differentiated thyroid cancer. Topics reviewed include definitions; staging; the 2 principal methods for selection of 131-I dosage; the indications for ablation, adjuvant treatment, and treatment; the recommendations for the use of 131-I contained in the guidelines of the American Thyroid Association and the Society of Nuclear Medicine and Molecular Imaging; the dosage recommendations and selection of dosage approach for 131-I by these organizations; the use of recombinant human thyrotropin for radioiodine ablation, adjuvant therapy, or treatment; and the MedStar Washington Hospital Center approach.
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Crucial parameters in thyroid carcinoma reporting - challenges, controversies and clinical implications.
Xu, B, Ghossein, RA
Histopathology. 2018;(1):32-39
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Abstract
In the modern era, a pathology report of thyroid carcinoma requires the inclusion of numerous prognostically relevant histopathological features, e.g. the presence and extent of vascular and capsular invasion, extrathyroidal extension, the surgical margin status and the characteristics of nodal metastasis. These pathological features are crucial components of the initial risk stratification to determine the need for completion thyroidectomy and/or postoperative radioactive iodine ablation therapy. The current review aims to summarise the diagnostic criteria, the controversies, the prognostic impacts and the challenges of these pathological characteristics, focusing specifically on the parameters that are incorporated into the American Joint Committee on Cancer (AJCC) staging system, the College of American Pathologists (CAP) reporting template, the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) guidelines.