bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and Difficulties in the Management of Thyroid Microcarcinoma in Algeri
Authors: Kaouache Nadjib , Billel Zouraghen 
Published: May 2021

Abstract
Introduction: Thyroid cancer prevalence has increased significantly in recent years, including in Algeria, which primarily concerned microcarcinoma making 30 to 50% of new diagnosed cases. Despite its good prognosis, its management remains highly controversial and debated. We aim to describe characteristics of thyroid microcarcinoma in a series from eastern Algeria monitored in the endocrinology department of Constantine University Hospital and to report the difficulties pertaining to its management. Patients and Methods: A descriptive retrospective study including patients followed and monitored in the thyroid cancer register in the endocrinology department of Constantine University Hospital during the period between January 2015 and December 2018. Results: Of 70 cases of thyroid microcarcinomas, mean age was 44 years [17-84 years] and 94% were women. 94% of the cases were papillary micro carcinomas; the two most frequent variants were the classic papillary and the vesicular variant of papillary carcinoma in 80% of cases. The diagnosis was made following a multi-nodular goiter exploration in 60% and thyroid function was normal in 50%. Moltifocality and bilaterality were reported in 27% and 5.71% of cases respectively. The most common surgical procedure was total thyroidectomy (96%), without lymph node dissection (86%). Classification of the initial risk was impossible due to the insufficient data in 28% of cases. 52% of patients received RAI therapy and 81% were in complete remission. Conclusion: Thyroid micro carcinoma has a good prognosis; however, its management faces several issues, mainly the stratification of risk which would be a source of overtreatment.
Clinical Outcomes of Differentiated Thyroid Cancer With Gross Extrathyroidal Extension Into the Strap Muscles: A Case Control Study
Authors: Chablani Sumedha , Ghaznavi Sana , Tuttle R Michael 
Published: May 2021

Abstract
Background: The 8th edition of the American Joint Committee on Cancer/tumor-node-metastasis (AJCC/TNM) staging system for differentiated thyroid cancer (DTC), implemented in January 2018, classifies patients &gt;/= 55 years of age with gross extrathyroidal extension (ETE) of the primary tumor into the overlying strap muscles as prognostic stage II. However, it remains controversial as to whether or not gross ETE into the strap muscles is an independent predictor of recurrence, response to therapy, need for additional therapies, or overall survival. Using a case control study design, we evaluated the prognostic significance of gross ETE among adults.
Methods: After obtaining IRB approval, we used the tumor registry at our institution to retrospectively identify 51 AJCC stage II patients with DTC aged &gt;/= 55 years with gross ETE into only the strap muscles (51/2,225 patients). For each of the 51 cases, we identified one control who matched on all of the following important prognostic factors: age at diagnosis (± 5 years), sex, histology, size of tumor (± 1 cm), lymph node metastases, distant metastases, completeness of resection, receipt of radioactive iodine (RAI) therapy, and duration of follow-up (± 5 years). The controls (n=51) had no gross ETE.
Results: In the 51 patients with gross ETE into only the strap muscles, the mean age at diagnosis was 64 years, 77% were female, 37% had lymph node metastases, and none had distant metastases. The average tumor size was 2.1 cm with the majority of patients (49/51) demonstrating papillary thyroid carcinoma (1 follicular thyroid carcinoma and 1 Hurthle cell thyroid carcinoma). Only 6% of patients (3/51) had incomplete resections and 92% (47/51) received RAI therapy. The mean duration of follow-up was 8 years.
There were no statistically significant differences between the cases and controls on each of the pre-specified prognostic variables described in the methods. In addition, there were no statistically significant differences between the groups in terms of rates of recurrence: cases 18% (9/51) and controls 29% (15/51) (p=0.24), best response to initial therapy (excellent, biochemical incomplete, structural incomplete, or indeterminate response to therapy), and need for subsequent interventions including surgery, RAI, external beam radiation, or systemic therapy. Furthermore, there were no statistically significant differences between the cases and controls with respect to 10-year disease-free survival (cases 83% and controls 68%, p=0.90) and 10-year overall survival (cases 97% and controls 89%, p=0.10).
Conclusions: In a case control analysis with a mean follow up of 8 years, the presence of ETE into the strap muscles was not an independent predictor of worse clinical outcomes in adults &gt;/= 55 years old with DTC. These findings can be used to inform the future editions of the AJCC/TNM and American Thyroid Association staging systems for DTC.
Effectiveness of Different Thyroid Stimulating Hormone Thresholds for Thyroid Hormone Withdrawal - Aided Radioiodine Ablation in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta - Analysis
Authors: Rojas Tatiana , Solis-Pazmino Paola , Lincango-Naranjo Eddy , Ledesma Tannya , Alvarado-Mafla Benjamin , Barrera Francisco J , Vega Jorge Luis Salazar , García Cristhian , Ponce Oscar J , Brito Juan Pablo 
Published: May 2021

Abstract
Background: Patients with differentiated thyroid cancer (DTC) may benefit of radioiodine ablation (RAI) to reduce the probability of thyroid cancer recurrence. Guidelines recommend that thyroid stimulating hormone (TSH) of &gt;30mIU/L before RAI to optimize treatment response. However, evidence regarding this recommendation is conflicting. We conducted a systematic review and meta-analysis to compare outcomes (thyroid cancer recurrence and survival at 10 years of follow up) of stimulated TSH threshold before RAI with primary analysis focus on &lt;30 mIU/L versus ≥30 mIU/L, and subgroup analysis on &lt;90 mIU/L versus ≥90 mIU/L in patients with DTC after initial total thyroidectomy.
Methods: The protocol for this study is registered and available online (CRD42020158354). Briefly, we searched several databases from their inception to April 2020. Reviewers, working independently and in duplicate selected studies for inclusion, extracted data, and evaluated each study’s risk of bias. We excluded studies that used recombinant human thyroid stimulating hormone before ablation. Results: We included five retrospective cohort studies, which enrolled a total of 2,514 patients. Risk of bias was low in four studies and high in one study. Mean age was 47 years old (ranged from 40.7 to 47.9) and most of them were female (69%). The most common DTC type was papillary thyroid cancer (78%). From those articles that reported tumor characteristics, 48% had a size ≤2cm (T1b) and 47% &gt;2cm. Moreover, 73% of the patients had no regional lymph metastasis (N0). Two studies reported radioiodine mean dose given of 30 and 100 mci. A total of 301 patients were included in the TSH threshold &lt;30 mIU/L group and 1788 patients in the TSH ≥30 mIU/L group. Comparing stimulated TSH threshold before RAI (&lt;30 mIU/L versus ≥30 mIU/L), there was difference in recurrence at 1 year (RR 2.46 (C.I. 1.09-5.55) and at 20 years (RR 1.71 (C.I. 1.19 – 2.47). However, there was no difference in mortality at 20 years (RR 0.53 (Confidence Interval (C.I.) 0.12-2.23). In addition, 10-years recurrence was not different when we compared &lt;90 mIU/L versus ≥90 mIU/L TSH (RR 1.06; 95%CI: 0.88 – 1.27).
Conclusions: Mortality do not differ between recommended TSH goal (≥30 mIU/L) vs &lt;30 mIU/L in thyroid hormone withdrawal-aided radioiodine ablation in DTC patients. However, the risk of recurrence is reduced when patients achieved a TSH level &gt;30 UI/mL. These results suggest that patients may need to reach a stimulated TSH ≥30 mIU/L stimulated TSH threshold to be treated. Randomized trials are needed to confirm these findings.
Interobserver Variability in Ultrasound Reporting - Tertiary Hospital Radiologists Do Better
Authors: Koch Noam , Applebaum Liat , Mazeh Haggi , Katz Lilach , Pollack Rena 
Published: May 2021

Abstract
Introduction: Thyroid Imaging Reporting and Data System (TI-RADS) was developed to provide a standardized risk-stratification system for patients with thyroid nodules. Single-center studies have demonstrated an acceptable level of interobserver agreement in applying TI-RADS in clinical practice, however data regarding consistency among different centers is limited. In Israel, thyroid nodules are initially evaluated by ultrasound performed by radiologists at the health maintenance organization (HMO) and then patients are referred to tertiary hospitals for ultrasound-guided fine needle aspiration (FNA) biopsy when indicated. Objective: To evaluate the interobserver concordance in TI-RADS classification system reporting between the HMO and a tertiary hospital. Methods: We performed a retrospective analysis of the sonographic features of 370 thyroid nodules TI-RADS category 2 or higher, from 350 patients evaluated by ultrasound at the HMO and at Hadassah Medical Center from January 1, 2018 to December 31, 2019. The primary outcome was concordance between the TI-RADS classification at the HMO compared to the hospital. Additional endpoints included correlation of TI-RADS to the Bethesda category following FNA, and correlation of TI-RADS with malignancy on final pathology. Results: Of 370 nodules, only 73 (19.8%) demonstrated concordance between the HMO and the hospital. The level of agreement was poor, with 277 (74.8%) nodules demonstrating higher TI-RADS at the HMO compared to the hospital, and 20 (5.4%) with lower TI-RADS at the HMO compared to the hospital (p&lt;0.001, weighted Kappa = 0.120). Of the nodules referred to the hospital, 241 (65.1%) were selected for FNA. A strong correlation between the hospital TI-RADS and Bethesda category was demonstrated (p&lt;0.001). Furthermore, 60 (16.2%) nodules were surgically removed. A strong correlation was identified between the hospital TI-RADS and malignancy on final pathology (p&lt;0.001), yet there was no correlation with the TI-RADS of the HMO (p=0.346). Conclusions: There is poor concordance between TI-RADS classification on ultrasound performed in the HMO compared to a tertiary hospital. In patients who underwent FNA and eventually surgery, the hospital TI-RADS strongly correlated with Bethesda category and final risk of malignancy. Standardization of thyroid ultrasound terminology and dedicated training in thyroid imaging are needed to improve the interobserver concordance in clinical practice.
Malignancy Risk in RAS-Mutated Cytologically Indeterminate Thyroid Nodules: Real-World Clinical Experience
Authors: Lu Joseph , Lupo Mark Armin 
Published: May 2021

Abstract
Introduction: Fine needle biopsy (FNB) is the standard procedure for thyroid nodules meeting criteria for biopsy according to current national guidelines (ATA and ACR). However, 15-25% of biopsies are categorized as indeterminate in the Bethesda Categories III (Atypical/FLUS) or IV (Follicular/Hurthle Neoplasm). Molecular testing is a common way to further risk stratify these nodules for surveillance versus surgical resection. BRAF-like mutations have a high probability of malignancy while RAS-like mutations have a variable risk of malignancy. This study examines the performance of RAS mutations in identifying malignancy or NIFTP in a real-world clinical setting.
Methods: 2,372 sequential thyroid FNBs were performed in our center from July 2014 to June 2020. Of these, 367 were subjected to molecular testing with either Thyroseq V2 or V3. 55 RAS-mutated BCIII or IV cases were identified and retrospectively evaluated. NIFTP was considered malignant in the calculations. ATA and ACR ultrasound classification as well as Doppler grade of the study nodule were assessed.
Results: 8 cases were excluded due to lack of follow-up or incomplete data. 40 underwent surgical resection based on the cytology and molecular results. 7 did not undergo surgery based on patient preference or comorbidities and had clinical follow up with stable ultrasound for at least 6 months. Surgical pathology results: 67.5% benign, 7.5% NIFTP and 25% malignant.
All 4 of the Thyroseq “currently negative” RAS nodules were benign. Of the 36 “positive” cases, 6 with additional mutations had a 66.7% ROM and the 30 RAS-only cases had a 30% ROM. Of the 9 RAS-only cases that were not benign, 3 were NIFTP, 5 FVPTC (2 unencapsulated and 3 encapsulated) and 1 was angio-invasive PTC with extensive extrathyroidal extension (this case had high-risk pre-op imaging features). None had lymph node involvement.
Higher allelic frequency, abnormal gene expression (GE) and copy number alterations (CNA) all increased the risk of malignancy/NIFTP; ROM was 50% when both GE and CNA were positive. Nodules that were ATA/ACR moderate and high suspicion had an approximately 40% and 67% ROM respectively with ATA and ACR performing similarly. High intra-nodular vascularity conferred a 46% ROM.
Conclusions: RAS mutations represent the most frequent abnormality found in oncogene testing however isolated RAS mutations have a low risk of malignancy and when malignant are generally non-aggressive. When both GE and CNA are positive, the risk increases. US features, including Doppler also contribute to risk assessment. Combining all these features is recommended when counseling patients on active surveillance versus surgical resection of RAS-mutated thyroid nodules.
Metabolic Factors Can Influence the Risk of Differentiated Thyroid Cancer
Authors: Dumitriu Roxana-Ioana , Burcea Iulia Florentina , Dusceac Roxana , Galoiu Simona , Poiana Catalina 
Published: May 2021

Abstract
Introduction: Worldwide, the increasing incidence of thyroid cancer, along with a parallel increase in obesity and metabolic disorders, suggests that modifications of lifestyle and environmental factors might explain the rise in thyroid cancer incidence (1). Objective: To investigate the association between metabolic syndrome and their elements and their possible association with the risk of thyroid cancer. Materials and Methods: We enrolled 200 patients, who underwent total thyroidectomy for multinodular goiter (Bethesda II-V categories on the basis of fine needle aspiration biopsy cytological examination). We included subjects with differentiated thyroid carcinoma, the ones with poorly differentiated, anaplastic, medullary thyroid carcinomas and secondary tumors were excluded from the analysis. Patients were divided into two groups, according to the post-surgical histological diagnosis: 60 patients diagnosed with papillary or follicular thyroid cancer and 60 diagnosed with benign thyroid disease. The patients had a mean age of 56.9 years old and the majority were females (90%). Relative risk of incident thyroid cancer was assessed by preoperative levels of body mass index (BMI), blood pressure, blood levels of glucose, cholesterol, triglycerides, and the presence of metabolic syndrome (according to the NCEP ATP III definition). The two groups had similar age, gender distribution, smoking habit. Mean BMI was slightly higher in the group with patients with differentiated thyroid cancer and the majority were obese (27.41 ± 5.38 kg/m2versus 26.42 ± 5.18 kg/m2). The patients from the differentiated thyroid cancer group showed a higher percentage of diabetes mellitus and impaired fasting glucose compared to the second group (20% versus 13%), with mean fasting blood sugar levels of 97 ± 2.69 mg/dl in the first group versus 73 ± 3.06 mg/dl in the second group. 30% of the patients from the differentiated thyroid cancer group presented criteria for metabolic syndrome. There was a positive correlation between the presence of hypertension and the diagnosis of differentiated thyroid cancer (p&lt;0.05). Conclusion: Our study showed a potential association between metabolic risk factors and the diagnosis of differentiated thyroid cancer. Besides the improvement of diagnosis, thyroid cancer increasing incidence is probably due to environmental factors and lifestyle modifications. As a future perspective of this study and based on the hypothesis of glucose dependency of many tumor types, another therapeutic strategy can involve diet (low-carbohydrate, high-fat) in order to target metabolism in tumors and alter the Walburg phenothype. Reference: (1). Mele, C., Samà, M. et al. (2019). Circulating adipokines and metabolic setting in differentiated thyroid cancer, Endocrine Connections, 8(7), 997-1006.
Pregnancy During Active Surveillance of Papillary Thyroid Microcarcinoma
Authors: Rosario Pedro Weslley , Mourão Gabriela Franco 
Published: May 2021

Abstract
Introduction: Most patients diagnosed with papillary thyroid microcarcinoma (microPTC) classified as low risk and therefore eligible for active surveillance (AS) are women. Although age is a predictor of tumor progression (more frequent among young people), young adults are “appropriate” candidates for AS. Consequently, a proportion of patients with low-risk microPTC eligible for AS are women of childbearing age and knowledge of the effect of pregnancy on tumor progression is therefore important. In the Japanese population, Ito et al. observed this progression in only 8% of pregnancies. None of the series on the outcomes of AS in western populations has so far reported the behavior of microPTC in women who became pregnant during AS. Methods: We have submitted patients with low-risk microPTC to AS. Our management has been not to interrupt AS, i.e., not to indicate surgery when the patient wishes to become pregnant. We report here the results of five patients who became pregnant during AS and their follow-up up to 6 months after delivery. Results: The patients were 26 to 36 years old (median 29 years) when they became pregnant. None of them had a history of radiation exposure, one had a family history of PTC, one had associated Hashimoto’s thyroiditis, and all of them had only one tumor focus and were considered “appropriate” (but not “ideal”) candidates for AS. In fact, when pregnancy was diagnosed, the patients continued to exhibit the criterion for AS according to our initial protocol (tumor ≤ 1.2 cm, no apparent lymph node metastases [LNM] or extrathyroidal extension [ETE] on ultrasonography [US]). All women were monitored by monthly measurement of TSH and levothyroxine (L-T4) was administered during pregnancy to maintain TSH between 0.1 and 1 mIU/L. US was performed when pregnancy was diagnosed (between 6 and 9 weeks of gestation), around 22 weeks, at the end of pregnancy, and 6 months after delivery. During the evaluations, none of the patients had apparent LNM or ETE on US. None of the patients exhibited tumor growth, defined as an increase in diameter ≥ 3 mm. Tumor growth ≥ 50% was observed in only one patient, with a small reduction after delivery. Conclusions: Our preliminary results suggest that pregnancy is not associated with a high risk of progression of low-risk microPTC and that the desire to get pregnant or pregnancy should not be an exclusion factor for AS. References: Effects of Pregnancy on Papillary Microcarcinomas of the Thyroid Re-Evaluated in the Entire Patient Series at Kuma Hospital. Ito Y, Miyauchi A, Kudo T et al. Thyroid 2016; 26:156-60 AND Active Surveillance in Adults with Low-Risk Papillary Thyroid Microcarcinomas: A Prospective Study. Rosario PW, Mourão GF, Calsolari MR. Horm Metab Res. 2019; 51:703-8.
The Genomic Landscape of Radioactive Iodine Refractory and Avid Papillary Thyroid Carcinomas
Authors: Al-Kuraya Khawla Sami , Siraj Sarah , Masoodi Tariq , Siraj Abdul Khalid , Azam Saud , Qadri Zeeshan , Al-Dayel Fouad 
Published: May 2021

Abstract
Background: Although, standard treatment of Papillary Thyroid Carcinoma (PTC), involving surgery followed by radioactive iodine (RAI) therapy, is curative for most patients, 5-20% of patients develop RAI refractory disease. The repertoire of genomic events enabling RAI refractory disease in PTC needs elucidating. Methods: Whole-exome sequencing was performed on 100 primary PTC tumours, consisting of 47 RAI refractory and 53 RAI avid tumours, with matched germline. The resulting somatic variants were analysed to compare the genomic landscape, driver events and clinically actionable events between RAI refractory and avid PTC. Results: RAI refractory primary tumours were significantly associated with later stage, positive involvement of surgical margins, presence of extrathyroidal extension, lymph node metastases and poorer 5-year disease-free survival. Mutational burden was significantly higher, with additional subclonal mutations in RAI refractory compared to avid PTC patients. RAI refractory primary tumours showed significantly stronger PD-L1 expression. Mutations and PD-L1 expression in RAI Refractory PTC tumours significantly correlated with mutational signatures related to defective DNA base and nucleotide excision repair pathways. Driver mutations were acquired earlier in RAI refractory than in avid primary tumours. Conclusions: We conclude that RAI refractoriness is gained early in PTC, and is significantly associated with a higher mutational burden, PD-L1 expression, and mutational signatures, which may serve as important prognostic factors and indicate suitability for treatment with immune checkpoint inhibitors.
Trabecular Bone Score in Women With Differentiated Thyroid Cancer
Authors: Araujo Sousa Barbara Erika Caldeira , Soares Maria Marta Sarquis , Silva Barbara Campolina , Kakehasi Adriana Maria , Pires Magda Carvalho 
Published: May 2021

Abstract
Introduction: Thyrotropin stimulating hormone (TSH) suppression in patients with differentiated thyroid cancer (DTC) aims to decrease the growth and proliferation of thyroid cancer cells. However, the effect of TSH suppressive therapy on bone microarchitecture remains undefined. Methods: Cross-sectional study including 43 women with DTC undergoing TSH suppressive therapy (sTSH) compared to 20 women also on levothyroxine therapy but with TSH in the low-normal range (nTSH) since the thyroid surgery. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA), and trabecular bone score (TBS) was evaluated using the TBS iNsigth software. The relationship between suppressive therapy-related parameters and bone parameters was investigated. Results: The TBS mean values were not significantly different in the sTSH and nTSH groups (1.273 ± 0.12 vs 1.307 ± 0.14, p = 0.7197). In both groups, postmenopausal women had degraded microarchitecture (TBS 1.216 ± 0.11 vs 1.213 ± 0.09, p = 0.9333), while premenopausal women had normal microarchitecture (1.328 ± 0.11 vs 1.401 ± 0.12, p = 0.195). The percentage of all postmenopausal women with degraded TBS was 54.7%, while the percentage of osteoporosis diagnoses was 16.1%. Body mass index (BMI) and menopausal status were the only variables associated with TBS and BMD. Conclusion: Long-term TSH suppressive therapy does not seem to be associated with deterioration of the trabecular microarchitecture in premenopausal women. However, lower TBS values were observed in postmenopausal women of both groups, even in those with nonsuppressive therapy. These data show that treatment with thyroid hormone in DTC can be detrimental to bone quality in postmenopausal women, regardless of whether TSH levels are maintained chronically suppressed or in the low-normal range.