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Background: Lymph node metastasis (LNM) in patients with papillary thyroid carcinoma (PTC) is common. This meta‐analysis assesses the diagnostic accuracy of computed tomography (CT), ultrasound (US), and CT + US in detecting central and lateral LNM. Methods: A systematic review and meta‐analysis was performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The area under the curve (AUC) for summary receiver operating curves (sROC) were compared. Results: The study population included 7902 patients with a total of 15 014 lymph nodes. Twenty‐four studies analyzed the sensitivity of the overall neck region in which dual CT + US imaging (55.9%) had greater sensitivities (p < 0.001) than either US (48.4%) or CT (50.4%) alone. The specificity of US alone (89.0%) was greater (p < 0.001) than CT alone (88.5%) or dual imaging (86.8%). The DOR for dual CT + US imaging was greatest (p < 0.001) at 11.134, while the AUCs of the three imaging modalities were similar (p > 0.05). Twenty‐one studies analyzed the sensitivity of the central neck region in which both CT (45.8%) and CT + US imaging (43.4%) had greater sensitivities (p < 0.001) than US alone (35.3%). The specificity of all three modalities was higher than 85%. The DOR for CT (7.985) was greater than US alone (4.723, p < 0.001) or dual CT + US imaging (4.907, p = 0.015). The AUC of both CT + US (0.785) and CT alone (0.785) were significantly greater (p < 0.001) than US alone (0.685). Of the 19 studies that reported lateral LNM, CT + US imaging sensitivity (84.5%) was higher than CT alone (69.2%, p < 0.001) and US alone (79.7%, p = 0.038). The specificity of all imaging techniques was all greater than 80.0%. CT + US imaging DOR (35.573) was greater than CT (20.959, p = 0.024) and US (15.181, p < 0.001) individually. The AUC of independent imaging was high (CT: 0.863, US: 0.858) and improved significantly when combined (CT + US: 0.919, p = 0.024 and p < 0.001, respectively). Conclusions: We report an up‐to‐date analysis elucidating the diagnostic accuracy of LNM detection by either CT, US, or in combination. Our work suggests dual CT + US to be the best for overall detection of LNM and CT to be preferable in detecting central LNM. The use of either CT or US alone may detect lateral LNM with acceptable accuracy, yet dual imaging (CT + US) significantly improved detection rates. [ABSTRACT FROM AUTHOR]

Background: The development of systemic treatment options leveraging the molecular landscape of advanced thyroid cancer is a burgeoning field. This is a multidisciplinary evidence‐based statement on the definition of advanced thyroid cancer and its targeted systemic treatment. Methods: An expert panel was assembled, a literature review was conducted, and best practice statements were developed. The modified Delphi method was applied to assess the degree of consensus for the statements developed by the author panel. Results: A review of the current understanding of thyroid oncogenesis at a molecular level is presented and characteristics of advanced thyroid cancer are defined. Twenty statements in topics including the multidisciplinary management, molecular evaluation, and targeted systemic treatment of advanced thyroid cancer are provided. Conclusions: With the growth in targeted treatment options for thyroid cancer, a consensus definition of advanced disease and statements regarding the utility of molecular testing and available targeted systemic therapy is warranted. [ABSTRACT FROM AUTHOR]

Objective: Primary tumour size (PTS) is known to be a significant prognostic factor in patients with papillary thyroid carcinoma (PTC) undergoing thyroidectomy. Although cutoff values of 2 and 4 cm are widely used in surgical extent decision and long‐term outcomes predictions, the effectiveness of arbitrary cutoff values in stratifying patients for target outcomes is questionable. This study aimed to determine new optimal cutoffs of PTS. Design, Patient And Measurements: Patients (n = 529) with PTC who underwent total thyroidectomy were retrospectively reviewed. After risk factor analysis for structural recurrence, the optimal cutoffs of PTS were automatically calculated using restricted cubic spline analysis and X‐tile software. Subgroups were classified based on the newly determined cutoff values. Both the recurrence‐free survival (RFS) and the proportion of patients in each response‐to‐therapy category, using the dynamic risk stratification system (DRS), were compared between the subgroups. Results: PTS was confirmed as an independent risk factor for structural recurrence. The optimal cutoff values were calculated as 1.4 and 3.0 cm. The subgroups stratified using these newly determined cutoffs showed significantly different RFS and DRS based on the response to initial therapy, but the subgroups classified using the cutoffs of 2 and 4 cm did not. Conclusions: The newly determined cutoff values of PTS may be useful in better stratifying patients with PTC undergoing thyroidectomy for target outcomes and can be considered as a new definition in staging and risk stratification systems. [ABSTRACT FROM AUTHOR]

Careful consideration of prophylactic central compartment dissection is required to ensure that its benefits outweigh its risks in the thyroid cancer. Sixteen prospective or retrospective studies were included. True positive, true negative, false positive, and false negative were extracted from each study. The diagnostic odds ratio of ipsilateral central lymph node metastasis (iCLNM) for predicting contralateral central lymph node metastasis (cCLNM) was 12.9237 (95% confidence interval [CI], 8.1595–20.4695). The area under the summary receiver operating characteristic curve was 0.854. The sensitivity, specificity, and negative predictive value were 0.8925 [0.8232–0.9368], 0.6884 [0.6311–0.7404], and 0.9802 [0.9631–0.9894], respectively. There were strong correlations between cCLNM and clinicopathologic characteristics. Ipsilateral central lymph node pathology is useful for predicting contralateral central compartment invasion in patients with thyroid cancer. In addition, clinicopathologic characteristics were associated with cCLNM in patients with unilateral thyroid cancer. [ABSTRACT FROM AUTHOR]

Over the past several decades, the approach to the diagnosis and management of patients with follicular cell‐derived thyroid cancer has evolved based on improved classification of patients better matching clinical outcomes, as well as advances in imaging, laboratory, molecular technologies and knowledge. While thyroid surgery, radioactive iodine therapy and TSH suppression remain the mainstays of treatment, this expansion of knowledge has enabled de‐escalation of therapy for individuals diagnosed with low‐risk well‐differentiated thyroid cancer; better definition of treatment choices for patients with more aggressive disease; and improved ability to optimize treatments for patients with persistent and/or progressive disease. Most recently, the advancement of knowledge regarding the molecular aspects of thyroid cancer has improved thyroid cancer diagnosis and has enabled individualized therapeutic options for selected patients with the most aggressive forms of the disease. Guidelines from multiple societies across the world reflect these changes, which focus on taking a more individualized approach to clinical management. In this review, we discuss the current more personalized approach to patients with follicular cell‐derived thyroid cancer and point toward areas of future research still needed in the field. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid receptor 5 (LPAR5) is involved in mediating thyroid cancer progression, but the underlying mechanism needs to be further revealed. In this study, we confirmed that LPAR5 is upregulated in papillary thyroid carcinoma (PTC), especially in BRAF‐like PTC, by analyzing The Cancer Genome Atlas (TCGA) database and performing immunohistochemistry assay in human thyroid cancer tissues. LPAR5‐specific antagonist TC LPA5 4 treatment inhibited CGTH‐W3, TPC‐1, B‐CPAP, and BHT‐101 cell proliferation, CGTH‐W3 and TPC‐1 cell migration significantly. In vivo, TC LPA5 4 treatment could delay CGTH‐W3 xenograft growth in nude mice. We also found that LPAR5‐specific antagonist TC LPA5 4, PI3K inhibitor wortmannin, or mTOR inhibitor rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH‐W3 and TPC‐1 cells. Stimulating CGTH‐W3 cells transfected with pEGFPC1‐Grp1‐PH fusion protein with LPA resulted in the generation of phosphatidylinositol (3,4,5)‐triphosphate, which indicates that PI3K was activated by LPA directly. The p110β‐siRNA instead of p110α‐siRNA transfection abrogated the increase of levels of phosphorylated Akt and S6K1 stimulated by LPA. Furthermore, immunoprecipitation assay confirmed an interaction between LPAR5 and p110β. Overall, we provide new insights that the downregulation of LPAR5 decreased the proliferation and migration phenotype via the PI3K/Akt pathway. Inhibition of LPAR5 or the PI3K/Akt signal may be a novel therapeutic strategy for treating thyroid cancer. [ABSTRACT FROM AUTHOR]

Background: Flexible fiberoptic laryngoscopy is performed prior to thyroid surgery to evaluate the function of the recurrent laryngeal nerve. We assess the cost‐effectiveness of preoperative laryngoscopy prior to total thyroidectomy for a low‐risk thyroid cancer patient without dysphonia. Methods: A decision tree analysis was performed from a third‐party payer perspective. We assessed the cost‐effectiveness of fiberoptic laryngoscopy prior to total thyroidectomy for T2N0M0 papillary thyroid carcinoma, such that an ipsilateral vocal fold paralysis alters the surgical plan to hemi‐thyroidectomy, when permissible, to avoid the risk of bilateral vocal fold paralysis. Results: Performing preoperative laryngoscopy to assess vocal fold function has an incremental cost‐effectiveness ratio (ICER) of 45 193 USD/QALY compared to no laryngoscopy. At a willingness‐to‐pay of 100 K/QALY, the intervention is cost‐effective if the incidence of vocal fold paralysis is at least 0.57%, or when the permissible rate of hemithyroidectomy in cases of incidental paralysis is at least 41%. Probabilistic sensitivity analysis shows that laryngoscopy is cost‐effective in 90.9% of cases. Conclusions: Fiberoptic laryngoscopy is a cost‐effective prior to total thyroidectomy in asymptomatic, low‐risk thyroid cancer patients. [ABSTRACT FROM AUTHOR]

Background: Lateral lymph node metastasis (LLNM) occurs in a few of papillary thyroid microcarcinoma (PTMC) cases by the time of diagnosis. Total thyroidectomy (TT) is recommended in the 2015 American Thyroid Association guidelines as the initial surgical procedure for thyroid carcinoma patients with clinically apparent cervical lymph node metastasis. However, none of the controlled studies have focused on the proper extent of surgery for patients who have PTMC with concomitant LLNM without gross extrathyroidal extension (ETE). Methods: A total of 2373 consecutive patients with PTMC were retrospectively reviewed. Finally, 129 unilateral PTMC patients with ipsilateral LLNM without gross ETE were enrolled in this study and classified into two groups: those who underwent unilateral lobectomy (LT) plus lymph node dissection (LND) (Group I) and those who underwent TT plus LND (Group II). Surgical outcomes and recurrence-free survival (RFS) during the follow-up period were compared between the two groups. Results: There were 62 patients in Group I and 67 patients in Group II. Cases in Group II had a longer median operation time (150 min vs. 120 min, p < 0.001) and a higher incidence of postoperative hypoparathyroidism (p < 0.001), especially permanent hypoparathyroidism, than cases in Group I. But the RFS showed no statistically significant difference (p = 0.6005) between the two groups during a median follow-up period of 60 months. Conclusion: Thyroid LT alone plus ipsilateral LND may be an optimum initial procedure for unilateral PTMC patients with ipsilateral LLNM without gross ETE. A long-term follow-up, prospective, randomized controlled trial is warranted. [ABSTRACT FROM AUTHOR]

Background: Primary squamous cell carcinoma of the thyroid (ThySCC) is a rare cancer, primarily described only in case reports. We aimed to characterize the prognosis of ThySCC and compare its oncologic behavior to other thyroid malignancies. Methods: The National Cancer Database was queried to identify patients with ThySCC, papillary, tall cell variant, poorly differentiated (PDTC), and anaplastic (ATC) subtypes of thyroid cancer treated from 2004 to 2015. Demographics, tumor characteristics, and treatments were compared by tumor type and assessed to identify independent predictors of overall survival (OS). Results: Of 123,684 patients included, 314 had ThySCC. ThySCC patients had a 5-year OS of 17.7%, more closely resembling ATC (8.3%) than PDTC or PTC. ThySCC and ATC patients had similar demographics, except ThySCC patients who were younger (68.0 vs. 70.2 years, p < 0.01). ThySCC tumors were smaller (mean 53.5 ± 45.7 vs. 69.5 ± 75.2 mm) with less frequent extrathyroidal extension (ETE) (64.0% vs. 73.8%), lymphovascular invasion (8.3% vs. 12.3%), and positive margins (22.0% vs. 28.3%) compared to ATCs (p < 0.05). ETE [HR 3.1 (95% CI 1.5–6.4), p < 0.05] and lymph node metastases [HR 2.2 (95% CI 1.2–4.0) p < 0.05] were independently associated with worse OS for ThySCC patients. Both ThySCC and ATC patients had similar surgical success rates, with R1 resection possible in 37.3% versus 35.0% of patients, respectively (p < 0.05). However, in contrast to ATC patients, adjuvant therapy was not associated with improved OS for ThySCC patients after complete resection. Conclusions: ThySCC has a poor prognosis, similar to ATC, but with fewer aggressive features and no apparent survival benefit with adjuvant therapy after complete macroscopic surgical resection. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer ( DTC) is the most common malignancy of the endocrine system. There has been a significant increase in its incidence over the past two decades attributable mainly to the use of more sensitive diagnostic modalities. Ultrasound-guided fine needle aspiration cytology is the mainstay of diagnosis of benign disorders and malignancy. However, approximately 20% of lesions cannot be adequately categorized as benign or malignant. In the postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed for the detection of disease recurrence. Unfortunately, Tg antibodies are common and interfere with Tg measurement in this subset of patients. Despite this limitation, Tg remains the sole widely used thyroid cancer biomarker in the clinical setting. In an attempt to bypass antibody interference, research has focused mainly on mRNA targets thought to be exclusively expressed in thyroid cells. Tg and thyroid stimulating hormone receptor ( TSHR) mRNA have been extensively studied both for discerning between benign disease and malignancy and in postoperative disease surveillance. However, results among reports have been inconsistent probably reflecting considerable differences in methodology. Recently, micro RNA (mi RNA) targets are being investigated as potential biomarkers in DTC. Mi RNAs are more stable molecules and theoretically are not as vulnerable as mRNA during manipulation. Initial results have been encouraging but large-scale studies are warranted to verify and elucidate their potential application in diagnosis and postoperative surveillance of thyroid cancer. Several other novel targets, primarily mutations and circulating cells, are currently emerging as promising thyroid cancer circulating biomarkers. Although interesting and intriguing, data are limited and derive from small-scale studies in specific patient cohorts. Further research findings demonstrating their value are awaited with anticipation. [ABSTRACT FROM AUTHOR]

Background Primary thyroid lymphoma (PTL) is uncommon, accounting for 2% to 5% of all thyroid malignancies. Papillary thyroid carcinoma (PTC) is the most frequent thyroid cancer. The coexistence of PTL and PTC is very rare, and the preoperative diagnosis is rather difficult. Methods A 41-year-old male patient complaining of fast painless thyroid enlargement for 2 months and a cervical mass for half a month was presented. Imaging demonstrated an enlarged thyroid and a mass in the thyroid. Results Surgery was conducted, and the final diagnosis of coexistence of PTL and PTC was confirmed by histopathological and immunohistochemical examination. The patient was then treated with cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone (CHOP) chemotherapy and radiotherapy. After 2 months of follow-up, no recurrence or metastasis was noted. Conclusion This rare case highlights the importance for physicians to keep PTL in mind for differential diagnosis in patients with sudden thyroid enlargement and who have clinical history of Hashimoto thyroiditis. © 2015 Wiley Periodicals, Inc. Head Neck 37: E109-E114, 2015 [ABSTRACT FROM AUTHOR]