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JAMA Otolaryngology-- Head & Neck... Jun 2015Reoperation for recurrent papillary thyroid cancer (PTC) can be associated with a high rate of complications and failure to provide lasting remission. Percutaneous... (Comparative Study)
Comparative Study Review
IMPORTANCE
Reoperation for recurrent papillary thyroid cancer (PTC) can be associated with a high rate of complications and failure to provide lasting remission. Percutaneous ethanol injection (PEI) may be an effective nonsurgical management option for locally recurrent PTC.
OBJECTIVE
This systematic analysis of the current literature compares the efficacy and complications related to PEI vs reoperative surgical intervention for treatment of locally recurrent PTC.
DATA SOURCES
Original studies were identified using the keywords "thyroid/ethanol" and "recurrent thyroid cancer/repeat surgery."
STUDY SELECTION
Studies evaluating reoperation or PEI for lymph node metastases in patients with primary surgery of total thyroidectomy with appropriate lymph node dissection where indicated were included in the analysis for both reoperation and PEI. Animal studies, single case reports, and studies with fewer than 10 lesions were excluded.
DATA EXTRACTION AND SYNTHESIS
Outcomes included interval to detection of recurrence, success and failure rates, recurrence rates, complication rates, and follow-up duration. Between-group outcome differences were calculated using random-effects models, and pooled data cross-tabulation and logistic regression analysis were used.
RESULTS
In all, 945 publications were identified, and 27 studies met the inclusion criteria. There were no studies that directly compared the 2 treatment techniques. A total of 1617 patients were included in this analysis; 168 (11.4%) were treated with PEI, and 1449 (88.6%) were treated with reoperation. Reoperation was successful in 94.8% of cases compared with an 87.5% success rate for PEI (odds ratio [OR], 2.58; 95% CI, 1.55-4.31; P < .001). The recurrence rates for PEI and reoperation at the site of the treated lesion or elsewhere in the neck were also similar (OR, 1.07; 95% CI, 0.65-1.77; P = .78). Reoperation was associated with a 3.5% pooled risk of complications, while PEI incurred a pooled risk of 1.2% (OR, 2.9; 95% CI, 0.72-12.3; P = .08). However, most studies did not report routine preoperative and postoperative laryngoscopies, an evaluation needed for accurate neural complication analysis associated with each procedure.
CONCLUSIONS AND RELEVANCE
High-quality, well-designed studies are needed to evaluate the feasibility of incorporating PEI into the treatment protocol of PTC. Although presently inferior to reoperation, PEI has the potential to be a widely accepted and effective nonsurgical treatment option for limited recurrent PTC in poor surgical candidates or patients seeking to avoid multiple reoperations.
Topics: Animals; Carcinoma; Carcinoma, Papillary; Ethanol; Humans; Injections, Subcutaneous; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Recurrence, Local; Reoperation; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome
PubMed: 25928119
DOI: 10.1001/jamaoto.2015.0596 -
International Journal of Clinical and... 2014To evaluate the risk factors influencing the recurrence of papillary thyroid carcinoma. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the risk factors influencing the recurrence of papillary thyroid carcinoma.
METHODS
This meta-analysis used MEDLINE (PubMed), EMBASE and CNKI including all cohort studies reporting the risk factors influencing the recurrence after the initial operation on PTC up to February 23, 2014. Software RevMan 5.2 was used for meta-analysis.
RESULTS
Thirteen studies with a total of 7048 patients were included in our meta-analysis. Of all variables, gender, extrathyroid extension, LNM, tumor size, distance metastasis, thyroid surgery types and 131-I given or not were significantly correlated with recurrence, While overall recurrence was similar between the group of ≤ 45 years and > 45 years, multifolicality and solitary. However, when stratified the participants by study location (ie, Asian including China, Korea, Japan, Western country including America, France, Italy, Australia), a statistically significant summary odds ratio for age were found in Western country but none in Asian.
CONCLUSION
The risk factors influencing recurrence includes male, extrathyroid extension, LNM, tumor size more than 2 cm, distance metastasis and subtotal thyroidectomy. However, selection of operation mode should be based on not only the recurrence but the comprehensive consideration of the clinical features.
Topics: Adult; Age Factors; Carcinoma; Carcinoma, Papillary; Chi-Square Distribution; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Odds Ratio; Risk Factors; Sex Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome; Tumor Burden
PubMed: 25337182
DOI: No ID Found -
BMC Gastroenterology Dec 2023Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN.
METHODS
In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model.
RESULTS
The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN.
CONCLUSIONS
AP is predictive of malignancy in patients with IPMN.
Topics: Male; Female; Humans; Carcinoma, Pancreatic Ductal; Pancreatitis; Retrospective Studies; Acute Disease; Pancreatic Intraductal Neoplasms; Adenocarcinoma, Mucinous; Pancreatic Neoplasms
PubMed: 38041073
DOI: 10.1186/s12876-023-02972-4 -
Clinical Gastroenterology and... Oct 2017It is not clear how best to manage patients with low-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas because little is known about IPMN progression... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
It is not clear how best to manage patients with low-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas because little is known about IPMN progression to cancer. We sought to determine the cumulative incidence of development of pancreatic cancer in persons with unresected IPMNs (particularly low-risk IPMNs).
METHODS
We performed a systematic search of the MEDLINE and Embase databases through November 30, 2016 for studies reporting the cumulative incidence of pancreatic cancer in patients with unresected IPMNs or studies that provided data in sufficient detail for us to calculate cumulative incidence values. We categorized patient series as studies on low-risk IPMNs (lesions without main pancreatic duct involvement or mural nodules) or non-low-risk IPMNs. We calculated meta-analytic cumulative incidence values for pancreatic cancer at 1, 3, 5, and 10 years of follow-up by using the inverse variance method and random-effects model.
RESULTS
Among 1514 articles screened, we identified 10 studies of low-risk IPMNs (n = 2411) and 9 studies of non-low-risk IPMNs (n = 825). In studies of low-risk IPMNs, the meta-analytic cumulative incidence values for pancreatic cancer were 0.02% at 1 year (95% confidence interval [CI], 0.0%-0.23%; I= 0.0%), 1.40% at 3 years (95% CI, 0.58%-2.48%; I = 58.5%), 3.12% at 5 years (95% CI, 1.12%-5.90%; I = 88.0%), and 7.77% at 10 years (95% CI, 4.09%-12.39%; I = 79.8%). These values were much higher in studies of non-low-risk IPMNs; cumulative incidence values for pancreatic cancer were 1.95% at 1 year (95% CI, 0.0%-5.99%; I = 84.2%), 5.69% at 3 years (95% CI, 1.10%-12.77%; I = 89.9%), 9.77% at 5 years (95% CI, 3.04%-19.27%; I = 92.0%), and 24.68% at 10 years (95% CI, 14.87%-35.90%; I = 74.3%). The pooled cumulative incidence steadily increased linearly as the follow-up duration increased.
CONCLUSIONS
In a systematic review and meta-analysis, we found that low-risk IPMNs have almost 8% chance of progressing to pancreatic cancer within 10 years, and higher-risk IPMNs have almost 25% chance of progressing to cancer in 10 years; incidence values increase linearly with time. Continued long-term surveillance is therefore vital for patients with low-risk IPMNs.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Disease Progression; Humans; Incidence; Pancreatic Neoplasms; Risk Assessment
PubMed: 28342950
DOI: 10.1016/j.cgh.2017.03.020 -
JAMA Otolaryngology-- Head & Neck... Feb 2022The use of ultrasonography (US) vs cross-sectional imaging for preoperative evaluation of papillary thyroid cancer is debated. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
The use of ultrasonography (US) vs cross-sectional imaging for preoperative evaluation of papillary thyroid cancer is debated.
OBJECTIVE
To compare thyroid US and computed tomography (CT) in the preoperative evaluation of papillary thyroid cancer for cervical lymph node metastasis (CLNM), as well as extrathyroidal disease extension.
DATA SOURCES
MEDLINE and Embase were searched from January 1, 2000, to July 18, 2020.
STUDY SELECTION
Studies reporting on the diagnostic accuracy of US and/or CT in individuals with treatment-naive papillary thyroid cancer for CLNM and/or extrathyroidal disease extension were included. The reference standard was defined as histopathology/cytology or imaging follow-up. Independent title and abstract review (2515 studies) followed by full-text review (145 studies) was completed by multiple investigators.
DATA EXTRACTION AND SYNTHESIS
PRISMA guidelines were followed. Methodologic and diagnostic accuracy data were abstracted independently by multiple investigators. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool independently and in duplicate. Bivariate random-effects model meta-analysis and multivariable meta-regression modeling was used.
MAIN OUTCOMES AND MEASURES
Diagnostic test accuracy of US and CT of the neck for lateral and central compartment CLNM, as well as for extrathyroidal disease extension, determined prior to study commencement.
RESULTS
A total of 47 studies encompassing 31 942 observations for thyroid cancer (12 771 with CLNM; 1747 with extrathyroidal thyroid extension) were included; 21 and 26 studies were at low and high risk for bias, respectively. Based on comparative design studies, US and CT demonstrated no significant difference in sensitivity (73% [95% CI, 64%-80%] and 77% [95% CI, 67%-85%], respectively; P = .11) or specificity (89% [95% CI, 80%-94%] and 88% [95% CI, 79%-94%], respectively; P = .79) for lateral compartment CLNM. For central compartment metastasis, sensitivity was higher in CT (39% [95% CI, 27%-52%]) vs US (28% [95% CI, 21%-36%]; P = .004), while specificity was higher in US (95% [95% CI, 92%-98%]) vs CT (87% [95% CI, 77%-93%]; P < .001). Ultrasonography demonstrated a sensitivity of 91% (95% CI, 81%-96%) and specificity of 47% (95% CI, 35%-60%) for extrathyroidal extension.
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that further study is warranted of the role of CT for papillary thyroid cancer staging, possibly as an adjunct to US.
Topics: Humans; Lymph Node Excision; Lymphatic Metastasis; Preoperative Period; Thyroid Cancer, Papillary; Thyroid Neoplasms; Tomography, X-Ray Computed; Ultrasonography
PubMed: 34817554
DOI: 10.1001/jamaoto.2021.3387 -
Journal of the ASEAN Federation of... 2023The majority of thyroid malignancies are differentiated thyroid carcinomas (DTCs). We examined the incidence, disease extent, recurrence and disease-specific mortality... (Review)
Review
BACKGROUND
The majority of thyroid malignancies are differentiated thyroid carcinomas (DTCs). We examined the incidence, disease extent, recurrence and disease-specific mortality (DSM) of DTC among Filipinos residing in the Philippines and Filipino immigrants.
METHODOLOGY
In accordance with the 2020 PRISMA statement, we performed a systematic literature search in MEDLINE, Google Scholar, EBSCO, Cochrane and Clinicaltrials.gov for the period January 1, 1980 until January 27, 2022. Pooled incidence rate ratio and pooled proportions of disease extent, recurrence and DSM were determined.
RESULTS
Literature search yielded 1,852 studies. Out of 26 articles retrieved, nine retrospective case controls and cohorts were included. Incidence of DTC was significantly higher in female Filipino immigrants compared with non-Hispanic whites (NHW). Distant metastases and recurrence were more common among Filipinos and Filipino immigrants compared with NHW. Limited data showed higher DSM in Filipino immigrants and NHW than Filipinos, which may be influenced by reporting bias.
CONCLUSIONS
This review supports the trend of increased incidence and recurrence of DTC among Filipinos, although case registries are essential to confirm these findings. In the setting of the newly released Philippine guidelines for DTC, prospective studies with active long-term follow-up will help detect any changes in the outcomes of DTC among Filipinos.
Topics: Humans; Female; Incidence; Retrospective Studies; Prospective Studies; Thyroid Neoplasms; Adenocarcinoma
PubMed: 37252408
DOI: 10.15605/jafes.038.01.14 -
Clinical Endocrinology Jul 2015Prophylactic central lymph node dissection (CLND) in clinically node-negative patients remains controversial, and predictive factors for central lymph node metastasis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prophylactic central lymph node dissection (CLND) in clinically node-negative patients remains controversial, and predictive factors for central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) are not well defined. Herein, we conducted a systematic review to quantify the clinicopathologic factors predictive for CLNM in patients with PTC.
METHODS
A systematic search of electronic databases (PubMed, Embase, Cochrane CENTRAL, Scopus and Wanfang Database) for studies published until July 2014 was performed. Cohort, case-control studies and randomized controlled trials that examined clinical risk factors of CLNM were included.
RESULTS
Twenty-five studies (4 prospective and 21 retrospective studies) involving 7,719 patients met final inclusion criteria. From the pooled analyses, male gender (OR 1.93, 95% CI 1.40 to 2.64), tumour multifocality (OR 1.93, 95% CI 1.62 to 2.30), tumour size >0.5 cm (OR 3.48, 95% CI 2.24 to 5.41), capsular invasion (OR 1.91, 95% CI 1.36 to 2.67), extrathyroidal extension (OR 2.42, 95% CI 1.58 to 3.71), lymphovascular invasion (OR 13.29, 95% CI 5.61 to 31.48) and lateral lymph node metastasis (OR 14.33, 95% CI 5.34 to 38.50) were significantly associated with increased risk of CLNM, while age >45 years (OR 0.65, 95% CI 0.51 to 0.83) and lymphocytic thyroiditis (OR 0.70, 95% CI 0.53 to 0.92) resulted in decreased risk of CLNM. Bilaterality and tumour location were not significantly associated with CLNM development (all P > 0.05).
CONCLUSIONS
Our analysis identified several clinicopathologic factors associated with CLNM. These findings may guide the necessity and extent of prophylactic CLND and ultimately improve the outcomes of patients with PTC.
Topics: Age Factors; Carcinoma; Carcinoma, Papillary; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Neck; Neck Dissection; Neoplasm Invasiveness; Risk Factors; Sex Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroiditis, Autoimmune; Tumor Burden
PubMed: 25130203
DOI: 10.1111/cen.12583 -
Pancreatology : Official Journal of the... 2016The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.
METHODS
A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.
RESULTS
MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.
CONCLUSIONS
Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.
Topics: Humans; Neoplasms, Cystic, Mucinous, and Serous; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 27681503
DOI: 10.1016/j.pan.2016.09.011 -
Human Pathology Feb 2024Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of...
BACKGROUND
Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of Endocrine and Neuroendocrine Tumors. This new entity has been minimally described in the literature, and additional cases classified as such are missing.
MATERIALS AND METHODS
Cases of DHGTCs diagnosed at our institution from 2012 to 2022 were identified, and the following were reviewed: cytologic and histologic diagnoses, ancillary testing, immunohistochemical staining, treatments, and patient outcomes. Immunohistochemical staining for Ki67 was performed on selected cases lacking this immunostain. A systematic literature review of the English literature on DHGTCs from 2013 to 2023 was performed using PubMed and Embase.
RESULTS
Case cohort included 32 cases of DHGTCs, with an average age of 52.6 years (range 17-84 years) and a male:female ratio of 1.3:1. All cases underwent fine needle aspiration (FNA) and were categorized by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as follows: 14 cases as malignant (43.8 %), 10 as follicular neoplasm (31.3 %), 5 as atypia of undetermined significance (15.6 %), 2 as suspicious for malignancy (6.2 %), and 1 as non-diagnostic (3.1 %). The average tumor size was 5.15 cm, and most were papillary thyroid carcinoma (28, 87.5 %), with classic subtype being the most common. Twenty-one cases revealed tumor necrosis and the mitotic activity in lesions without necrosis averaged to 5.5 mitoses per 2 mm (range 0-7). The average Ki67 proliferative index was 5.6 %. Extrathyroidal extension was seen in 17, angioinvasion in 21, lymphatic invasion in 7, and perineural invasion in 1 case. Foci of solid or trabecular growth were identified in five cases. Lymph node metastases at the time of diagnosis were noted in 10 cases and 7 demonstrated distant metastases or locoregional recurrence. To date, 25 patients are alive, and one has died from disease.
CONCLUSIONS
Our institutional experience demonstrates that DHGTC is a rare, but aggressive thyroid tumor subtype that requires consideration in the setting of a well-differentiated thyroid neoplasm to appropriately assess for possible disease recurrence and determination of patient prognosis.
Topics: Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Ki-67 Antigen; Thyroid Neoplasms; Thyroid Cancer, Papillary; Necrosis; Adenocarcinoma, Follicular; Retrospective Studies
PubMed: 38244615
DOI: 10.1016/j.humpath.2024.01.002 -
Thyroid : Official Journal of the... Mar 2024The current edition of the World Health Organization (WHO) classification of endocrine tumors introduced grading for follicular cell-derived thyroid cancer. Tumors with... (Meta-Analysis)
Meta-Analysis
The current edition of the World Health Organization (WHO) classification of endocrine tumors introduced grading for follicular cell-derived thyroid cancer. Tumors with necrosis and/or high mitotic count but not fulfilling the Turin criteria for poorly differentiated carcinoma will be reclassified as differentiated high-grade thyroid carcinoma (DHGTC). However, the impact of this reclassification has not been evaluated. In this study, we performed a systematic review and meta-analysis to estimate the prevalence of this new entry across thyroid tumor subtypes. In this systematic review and meta-analysis, studies reporting data on necrosis and/or mitoses in well-differentiated thyroid carcinoma (WDTC) were used to estimate the prevalence of DHGTC. Heterogeneity and potential publication bias were also evaluated. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and quality assessment was performed using a modification of the Newcastle-Ottawa scale. The study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022378716). In clinically unselected patients, the prevalence of DHGTC in WDTC was 0.072 [95% confidence interval, CI, = 0.045-0.113]. The proportion of high-grade tumors greatly varied across growth patterns and subtypes. Overall, the prevalence of DHGTC was higher in follicular thyroid carcinoma (FTC; 0.146 [CI = 0.101-0.205]) than in papillary thyroid carcinoma (PTC; 0.059 [CI = 0.036-0.097]). Diffuse sclerosing, follicular, and classic subtype PTC had the lowest rates of high-grade features (i.e., 0.018 [CI = 0.004-0.084]; 0.036 [CI = 0.010-0.124]; and 0.042 [CI = 0.027-0.066], respectively), while a greater proportion of solid trabecular and histologically aggressive PTC could be reclassified as DHGTC (i.e., 0.154 [CI = 0.067-0.314] and 0.168 [CI = 0.108-0.252], respectively). Similar proportions were obtained for minimally and widely invasive FTC (i.e., 0.136 [CI = 0.058-0.287] and 0.152 [CI = 0.086-0.254], respectively). Finally, in a cohort of patients with poor prognosis (i.e., fatal cases, metastatic and radioiodine resistant tumors, cases with biochemical recurrence), the proportion of DHGTC was 0.287 [CI = 0.155-0.469]. Following the current WHO indications, some tumors will be reclassified as DHGTC. The proportion of tumors with high-grade features is relevant in FTC, solid trabecular, and histologically aggressive PTC subtypes. A remarkable enrichment in DHGTC among patients with poor prognosis confirms the negative impact of high-grade features on outcome.
Topics: Humans; Iodine Radioisotopes; Prevalence; Thyroid Neoplasms; Adenocarcinoma, Follicular; Necrosis
PubMed: 38115626
DOI: 10.1089/thy.2023.0350