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European Archives of... Feb 2024Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC.
METHODS
The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software.
RESULTS
A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04-4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19-0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95-7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93-16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61-11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46-3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90-7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35-0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72-4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11-11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54-8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37-8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64-12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98-1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74-1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16-27.43, P < 0.00001).
CONCLUSION
Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients.
Topics: Humans; Calcitonin; Lymphatic Metastasis; Carcinoembryonic Antigen; Thyroid Neoplasms; Lymph Nodes; Risk Factors; Retrospective Studies; Carcinoma, Neuroendocrine
PubMed: 37801162
DOI: 10.1007/s00405-023-08249-6 -
American Journal of Surgery Aug 2022Many patients with Medullary Thyroid Cancer (MTC) will have persistent or recurrent disease after surgery requiring lifelong surveillance with imaging and tumor markers.... (Review)
Review
BACKGROUND
Many patients with Medullary Thyroid Cancer (MTC) will have persistent or recurrent disease after surgery requiring lifelong surveillance with imaging and tumor markers. The objective of this study is to evaluate the efficacy of Ga-DOTATATE-PET (or Ga labelled equivalent radiopharmaceutical) versus F-FDG-PET for detecting persistent and/or metastatic recurrent MTC.
METHODS
Relevant studies were identified by conducting searches in Embase and PubMed and five studies were included in the final review.
RESULTS
Five studies investigated per-patient sensitivity of F-FDG-PET and Ga-DOTATATE-PET in MTC patients. Four studies investigated the correlation between calcitonin and number of lesions detected by F-FDG-PET and Ga-DOTATATE-PET, and three investigated the correlation between CEA and number of lesions detected by F-FDG-PET and Ga-DOTATATE-PET. There was no significant difference in number of lesions detected by F-FDG -PET compared with Ga-DOTATATE-PET.
CONCLUSIONS
When compared directly to F-FDG-PET, there is a general trend towards favoring Ga-DOTATATE-PET in per-patient sensitivities, and incidence of lesion detection.
Topics: Carcinoma, Neuroendocrine; Fluorodeoxyglucose F18; Gallium Radioisotopes; Humans; Positron-Emission Tomography; Radionuclide Imaging; Radiopharmaceuticals; Thyroid Neoplasms
PubMed: 35382933
DOI: 10.1016/j.amjsurg.2022.03.046 -
Thyroid Research Dec 2021Hashimoto thyroiditis (HT) is the most common inflammatory autoimmune thyroid disease and also the most common cause of hypothyroidism in developed countries. There is... (Review)
Review
BACKGROUND AND PURPOSE
Hashimoto thyroiditis (HT) is the most common inflammatory autoimmune thyroid disease and also the most common cause of hypothyroidism in developed countries. There is evidence of the role of HT in developing thyroid cancers (TCs). This study investigated the association between HT and different types of TCs.
METHODS
Results of a comprehensive search in three major databases, as well as hand searching, were screened in title/abstract and full-text stages and the relevant data were extracted from the studies that met the inclusion criteria. Risk of bias (RoB) was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools and the meta-analysis was conducted with Comprehensive Meta-Analysis software.
RESULTS
Out of 4785 records, 50 studies were included in the systematic review, and 27 of them met the criteria for quantitative synthesis. The results indicated a significant role for HT in developing papillary TC (OR: 1.65; 95% CI: 1.04 to 2.61), medullary TC (OR: 2.70; 95% CI: 1.20 to 6.07) and lymphoma (OR:12.92; 95% CI: 2.15 to 77.63); but not anaplastic TC (OR: 1.92; 95% CI: 0.29 to 1.90) and follicular TC (OR: 0.73; 95% CI: 0.41 to 1.27). Also, this study found a significant association between HT and thyroid malignancies (OR: 1.36; 95% CI: 1.05 to 1.77).
CONCLUSION
Although we found a significant association between HT and some types of TCs, High RoB studies, high level of heterogeneity, and the limited number of well-designed prospective studies, suggested the need for more studies to reach more reliable evidence.
PubMed: 34861884
DOI: 10.1186/s13044-021-00117-x -
European Journal of Endocrinology May 2015Many tyrosine kinase inhibitors (TKIs) have been studied in patients with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in differentiated TC... (Meta-Analysis)
Meta-Analysis Review
Therapy of endocrine disease: response and toxicity of small-molecule tyrosine kinase inhibitors in patients with thyroid carcinoma: a systematic review and meta-analysis.
CONTEXT
Many tyrosine kinase inhibitors (TKIs) have been studied in patients with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in differentiated TC (DTC) and medullary TC (MTC) patients have not been directly compared. The aim of the present systematic review and meta-analysis was to systematically summarize response and toxicity of TKIs in TC patients.
METHODS
All major databases were systematically searched for publications on TKIs in TC. Primary endpoint was objective response; secondary endpoints were clinical benefit, percentage TKI dose reduction/discontinuation, hand-foot syndrome, diarrhea, and nausea/vomiting. Meta-analysis was performed using an exact likelihood approach and a logistic regression. Pooled percentages and 95% CIs were reported.
RESULTS
In total, 22 publications were included. For DTC patients, gefitinib induced no objective responses. Pooled percentage was highest for pazopanib, 49 (95% CI 33-64)%, and was 17 (95% CI 12-24)% for sorafenib. For MTC, gefitinib and imatinib induced no objective responses, whereas sunitinib induced objective response in 43 (95% CI 14-77)%. For vandetanib and cabozantinib, these numbers were 40 (95% CI 34-46)% and 27 (95% CI 22-32)% respectively. Clinical benefit was found in 53 (95% CI 48-59)% of DTC patients on sorafenib, and in 84 (95% CI 79-88)% and 55 (95% CI 49-61)% of MTC patients on vandetanib and cabozantinib respectively. All TKIs were associated with considerable toxicity.
CONCLUSION
The currently studied TKIs show a modest response, while side effects are not negligible. Therefore, we suggest to solely consider TKIs in TC patients with rapid progressive disease, for whom the benefits of treatment outweigh toxicity.
Topics: Antineoplastic Agents; Humans; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Thyroid Neoplasms
PubMed: 25572389
DOI: 10.1530/EJE-14-0788 -
Pathology, Research and Practice Jan 2022Medullary thyroid cancer (MTC) is the third frequent subtype of thyroid cancer-driving from thyroid C-cells. The first-line strategy to treat MTC is surgery, but tumor...
Medullary thyroid cancer (MTC) is the third frequent subtype of thyroid cancer-driving from thyroid C-cells. The first-line strategy to treat MTC is surgery, but tumor recurrence and patients' mortality rate have still been demonstrated in approximately 4-10% of MTC cases. Therefore, to treat and prevent the progressive form of the disease, the early diagnosis of MTC is assumed to play a critical role. In this regard, recently, circulating biomarkers have drawn researchers' attention for their nonaggressive manners in the sample collection. In this systematic review, we aimed to focus on circulating biomarkers and their applications in MTC diagnosis, prognosis and follow-up, and we discussed their clinical application and how they can affect clinical decision making in the future. A literature search (from 2000 to 2021) was accomplished on MTC circulating biomarkers in different databases, and only English articles were evaluated. We found that calcitonin (CT) and carcinoembryonic antigen (CEA) are the most important circulating biomarkers in the MTC diagnosis. Other circulating biomarkers included pro-calcitonin (Pro-CT), pro-Gastrin releasing peptide (Pro-GRP), carbohydrate antigen 19-9 (CA 19-9) and chromogranin A (CgA). Some novel circulating biomarkers comprised vaspin and retinol-binding protein-4 (RBP4), myostatin, tumor cells (CTCs), RET M918T mutated cfDNA, circulating tumor DNA (ctDNA), miR-375 and Alu83 and Alu244 cfDNAs. Several circulating biomarkers have been identified to optimize the accuracy of diagnosis and offer new prognostic criteria, which should be verified before any clinical application. Although different circulating biomarkers contributed to MTC have been discovered, a few of them could be used in clinical diagnosis. In many cases, the application of each marker may not be useful lonely; therefore, a combination of two or more biomarkers could open a new avenue in the diagnosis, prognosis and prediction of MTC.
Topics: Biomarkers, Tumor; Carcinoma, Neuroendocrine; Humans; Prognosis; Thyroid Neoplasms
PubMed: 34929598
DOI: 10.1016/j.prp.2021.153694 -
Clinical Endocrinology Nov 2022Ultrasound (US) is the pivotal procedure during the diagnostic work-up of thyroid nodule and several US-based risk stratification systems (RSSs) have been recently... (Meta-Analysis)
Meta-Analysis Review
Suboptimal accuracy of ultrasound and ultrasound-based risk stratification systems in detecting medullary thyroid carcinoma should not be overlooked. Findings from a systematic review with meta-analysis.
OBJECTIVE
Ultrasound (US) is the pivotal procedure during the diagnostic work-up of thyroid nodule and several US-based risk stratification systems (RSSs) have been recently developed. Since the performance of RSSs in detecting medullary thyroid carcinoma (MTC) has been rarely investigated, the present systematic review aimed to achieve high evidence about (1) how MTC is classified according to RSSs; (2) if RSSs correctly classify MTC at high risk/suspicion, and (3) if MTC is classified as suspicious at US when RSSs are not used.
DESIGN
The review was performed according to MOOSE. The online search was performed by specific algorithm on January 2022. A random-effects model was used for statistical analysis.
RESULTS
Twenty-five papers were initially included and their risk of bias was generally low. According to ATA system, 65% of MTCs was assessed at high suspicion and 25% at intermediate suspicion. Considering all RSSs, a 54.8% of MTCs was put in a high-risk/suspicion category. Pooling data from studies without data of RSS the prevalence of ultrasonographically suspicious MTCs was 60%.
CONCLUSIONS
As conclusion, MTC presentation according to RSSs is partially known and it is classified in a high-risk/suspicion category of RSSs in just over a half of cases. This advises for further studies, ideally supported by international societies, to better define the US presentation of MTC.
Topics: Carcinoma, Neuroendocrine; Humans; Risk Assessment; Thyroid Neoplasms; Thyroid Nodule
PubMed: 35419855
DOI: 10.1111/cen.14739 -
Thyroid : Official Journal of the... Aug 2016The 2015 American Thyroid Association (ATA) thyroid nodule guidelines recommend selecting nodules for biopsy based on a sonographic pattern classification. These... (Meta-Analysis)
Meta-Analysis Review
New American Thyroid Association Sonographic Patterns for Thyroid Nodules Perform Well in Medullary Thyroid Carcinoma: Institutional Experience, Systematic Review, and Meta-Analysis.
BACKGROUND
The 2015 American Thyroid Association (ATA) thyroid nodule guidelines recommend selecting nodules for biopsy based on a sonographic pattern classification. These patterns were developed based on features of differentiated thyroid cancer. This study aimed to evaluate the performance and the inter-observer agreement of this classification system in medullary thyroid carcinoma (MTC).
METHODS
The medical records of all patients with MTC evaluated at the authors' institution between 1998 and 2014 were retrospectively reviewed. Only patients with presurgical thyroid ultrasound available for review were included in the study. Five independent reviewers assessed the stored ultrasound images for composition, echogenicity, margins, presence of calcifications, and extrathyroidal extension for each nodule. The presence of suspicious lymph nodes was also evaluated when presurgical lateral neck ultrasound was available for review. Each nodule was classified according to the ATA sonographic patterns. Inter-observer agreement was calculated for each sonographic feature and for the sonographic patterns. To validate the findings, a systematic review of the literature and meta-analysis on the sonographic features of MTC was conducted.
RESULTS
In this institutional cohort, the inter-observer agreement for individual sonographic features was moderate to good (κ = 0.45-0.71), and for the ATA classification it was good (κ = 0.72). Ninety-seven percent (29/30) of the MTCs were classified in the intermediate or high suspicion patterns. A total of 249 MTCs were included in the meta-analysis. Based on pooled frequencies for solid composition and hypoechogenicity, >95% of MTCs would be classified at least in the intermediate suspicion pattern, warranting the lowest-size threshold for biopsy (≥1 cm).
CONCLUSIONS
The sonographic patterns proposed by the ATA perform well in MTC, and inter-observer agreement is good to very good.
Topics: Carcinoma, Medullary; Humans; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography; United States
PubMed: 27267210
DOI: 10.1089/thy.2016.0196 -
Clinical Endocrinology May 2024Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the... (Review)
Review
INTRODUCTION
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate.
METHODS
A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines.
RESULTS
Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old.
CONCLUSION
Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.
Topics: Humans; Carcinoma, Neuroendocrine; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy; Practice Guidelines as Topic
PubMed: 38472743
DOI: 10.1111/cen.15041 -
Endocrinology and Metabolism (Seoul,... Jun 2018Calcitonin measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other potential markers have...
BACKGROUND
Calcitonin measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other potential markers have been proposed, and procalcitonin (ProCT) has been reported as promising. The present study was undertaken to summarize the published data and provide more robust estimates on the reliability of ProCT as marker in the management of patients with MTC.
METHODS
The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The sources comprised studies published through May 2018. Journal Articles that reported series of MTC patients undergone ProCT during postoperative follow-up were searched. A random-effects model was used for statistical pooling of the data. The I² index was used to quantify the consistency among the studies. The Egger test evaluated the possible presence of significant publication bias. Quality assessment of the studies was performed according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).
RESULTS
According to inclusion and exclusion criteria five papers, reporting 296 MTC patients undergone ProCT evaluation, were finally selected. The number of MTC with recurrence was 140. The pooled sensitivity of ProCT in detecting recurrence was 96% (95% confidence interval [CI], 92% to 99%), with neither heterogeneity (I²=0%) nor publication bias (Egger test, 3.16; P=0.99). The pooled specificity was 96% (95% CI, 87% to 100%) with mild heterogeneity (I²=66.6%), while Egger test was not calculable.
CONCLUSION
The present meta-analysis provides evidence that ProCT is reliable to manage MTC patients during their postoperative follow-up.
PubMed: 29947178
DOI: 10.3803/EnM.2018.33.2.204 -
Endocrine Jan 2022The sensitivity of cytology after fine needle aspiration (FNA-cytology) in detecting medullary thyroid carcinoma (MTC) is low. To overcome this problem, measuring... (Meta-Analysis)
Meta-Analysis
Head-to-head comparison of FNA cytology vs. calcitonin measurement in FNA washout fluids (FNA-CT) to diagnose medullary thyroid carcinoma. A systematic review and meta-analysis.
PURPOSE
The sensitivity of cytology after fine needle aspiration (FNA-cytology) in detecting medullary thyroid carcinoma (MTC) is low. To overcome this problem, measuring calcitonin (CT) in washout fluid of FNA (FNA-CT) has been largely diffused and showed good performance. However, no evidence-based study exists comparing systematically the sensitivity of FNA-cytology and FNA-CT. This study aimed to systematically review the literature and collect data allowing a head-to-head comparison meta-analysis between FNA-cytology and FNA-CT in detecting MTC lesions.
METHODS
The online databases of PubMed/MEDLINE and Scopus were searched until June 2021. Original articles reporting the use of both FNA-cytology and FNA-CT in the same series of histologically proven MTC lesions were included They were extracted general features of each study, number of MTC lesions (nodule and neck lymph nodes), and true positive and false negatives of both FNA-cytology and FNA-CT.
RESULTS
Six studies were included. The sensitivity of FNA-cytology varied from 20% to 86% with a pooled value of 54% (95% CI 35-73%) and significant heterogeneity. The sensitivity of FNA-CT was higher than 95% in almost all studies with a pooled value of 98% (95% CI 96-100%) without heterogeneity. The sensitivity of FNA-CT was significantly higher than that of FNA-cytology.
CONCLUSIONS
FNA-CT is significantly more sensitive than FNA-cytology in detecting MTC. Accordingly, FNA-CT represents the standard method to use in patients with suspicious MTC lesions, combined with cytology.
Topics: Biopsy, Fine-Needle; Calcitonin; Carcinoma, Neuroendocrine; Humans; Thyroid Neoplasms; Thyroid Nodule; Tomography, X-Ray Computed
PubMed: 34606057
DOI: 10.1007/s12020-021-02892-x