Association of Parathyroid and Differentiated Thyroid Carcinomas: A Narrative Up-To-Date Review of the Literature.

Aim: Parathyroid carcinoma (PC) is a rare endocrine malignancy that represents 0.005% of all malignant tumors. Associated PC and differentiated thyroid carcinoma (DTC) is an exceptionally rare condition, and the preoperative diagnostics and proper treatment are challenging. Almost all PCs and the majority of DTCs are diagnosed postoperatively, making correct surgical treatment questionable. Specific guidelines for parathyroid and thyroid carcinomas association treatment are lacking. The purposes of our study were to identify the association between parathyroid and thyroid carcinomas, to analyze the available published data, and to evaluate the possible relationship between preoperative diagnostic and surgical decision-making, and outcome-related issues. Material and methods: We performed a literature review of several databases from the earliest records to March 2022, using controlled vocabulary and keywords to search for records on the topic of PC and WDTC pathological association. The reference lists from the initially identified articles were analyzed to obtain more references. Results: We identified 25 cases of PC and DTC association, 14 more than the latest review from 2021. The mean age of patients was 55, with a female to male ratio of about 3:1. Exposure to external radiation was identified in only one patient, although it is considered a risk factor the development of both PC and DTC. The preoperative suspicion of PC was stated by the authors in only 25% of cases, but suspicion based on clinical, laboratory, ultrasound (US), and fine needle aspiration (FNA) criteria could have been justified in more than 50% of them. With neck ultrasound, 40% of patients presented suspicious features both for PC and thyroid carcinoma. Intra-operatory descriptions of the lesions revealed the highest suspicion (83.3%) of PC, but en bloc resection was recommended and probably performed in only about 50% of the cases. Histopathological examinations of the thyroid revealed different forms of papillary thyroid carcinoma (PTC) in most cases. Postoperative normocalcemia was achieved in 72% of patients, but follow-up data was missing in about 25% of cases. Conclusion: Associated PC and DTC is an exceptionally rare condition, and the preoperative diagnostic and treatment of the patients is a challenge. However, in most cases pre- and intraoperative suspicious features are present for identification by a highly specialized multidisciplinary endocrine team, who can thus perform the optimal treatment to achieve curability.

Molecular mechanisms of resistance to kinase inhibitors and redifferentiation in thyroid cancers.

Protein kinases play critical roles in cell survival, proliferation, and motility. Their dysregulation is therefore a common feature in the pathogenesis of a number of solid tumors, including thyroid cancers. Inhibiting activated protein kinases has revolutionized thyroid cancer therapy, offering a promising strategy in treating tumors refractory to radioactive iodine treatment or cytotoxic chemotherapies. However, despite satisfactory early responses, these drugs are not curative and most patients inevitably progress due to drug resistance. This review summarizes up-to-date knowledge on various mechanisms that thyroid cancer cells develop to bypass protein kinase inhibition and outlines strategies that are being explored to overcome drug resistance. Understanding how cancer cells respond to drugs and identifying novel molecular targets for therapy still represents a major challenge for the treatment of these patients.

Poorly Differentiated Thyroid Carcinoma: Single Institution Series of Outcomes.

BACKGROUND AND AIM: Poorly differentiated thyroid cancer (PDTC) is a rare but aggressive subtype of thyroid cancer that portends a poor prognosis. There remains a paucity of literature on PDTC outcomes. The aim of our study was to evaluate outcomes of PDTC in our tertiary care facility. PATIENTS AND METHODS: We identified all histologically confirmed PDTC cases from 1997-2018 treated at our Institution and collected data points in an IRB-approved registry. We then conducted a retrospective study to assess outcomes and identified factors associated with inferior outcomes. RESULTS: Twenty-three patients were identified with a median age at diagnosis of 60 years (range=39-89 years). Nineteen (83%) underwent total thyroidectomy. Eight (42%) patients had lymph node dissections and 2 (11%) underwent adjuvant radiation. Thirteen (68%) patients were treated with radioactive iodine (RAI). Those who underwent total thyroidectomy had a median overall survival (mOS) of 88 months, 5 year-OS of 56%, 5 year-local recurrence-free survival (LRFS) of 45%, and 5 year-distant recurrence-free survival (DRFS) of 36%. T4 disease had worse mOS (14 vs. 87 m, p=0.0082), and 5 year-LRFS rate (12 vs. 74%, p=0.0312) compared to T1-3. N0 disease had an improved mOS (172 vs. 32 m, p=0.0013), 5 year-LRFS rate (63 vs. 17%, p=0.0033), and 5 year-DRFS (57 vs. 0%, p=0.0252). Eight out of 23 patients (35%) were alive at last follow-up, with a median of 68 months (range=20-214). The most common cause of death was distant recurrence (73%). Six patients received systemic therapy with various tyrosine kinase inhibitors with a median duration on treatment of 7 months (range=1-30 months). CONCLUSION: Advanced T and N stage were factors associated with significantly inferior outcomes. While select patients benefited with systemic treatment, it remains unclear if intensified locoregional therapy should be considered in patients with PDTC.

Comparison of Supraclavicular Oblique Incision With Traditional Low Collar Incision Approach for Thyroidectomy in Differentiated Thyroid Cancer.

Background: Various incisions and approaches for thyroidectomy have been developed to treat differentiated thyroid cancer (DTC). Supraclavicular oblique incision (SOI) thyroidectomy (SOIT) has been applied in DTC patients over the past ten years. However, the safety and efficacy of this approach were yet to be confirmed. Aim: This study aimed to compare the surgical and patient-related outcomes between SOIT and traditional low collar incision thyroidectomy (TLCIT) in patients with DTC. Methods: We retrospectively screened all patients with DTC who received thyroid lobectomy from October 2020 to October 2021. The surgical results and patient-related outcomes assessed at 1 and 6 months after surgery by questionnaire were compared between the SOIT and TLCIT groups. Results: A total of 128 patients were included in this study, of whom 38 patients (30.5%) were operated on with SOIT and 89 patients (69.5%) with TLCIT. There was no significant difference in demographic characteristics and thyroid features between the two groups. Despite comparable operative time (61.9 ± 12.1 vs. 59.9 ± 15.0 min, p = 0.425), the SOIT group had a smaller neck incision (4.4 ± 0.7 vs. 5.0 ± 1.0 cm, p = 0.002), a shorter duration of postoperative drainage (2.4 ± 0.5 vs. 2.7 ± 0.9 days, p = 0.019), less volume of postoperative drainage (48.4 ± 24.6 vs. 60.3 ± 22.8 ml, p = 0.040), and shorter postoperative hospitalization (3.2 ± 0.5 vs. 3.6 ± 0.9 days p = 0.006), as compared with the TLCIT group. At 1-month follow-up after surgery, SOIT showed better performance in preventing hypoparathyroidism (p = 0.026) and abnormal neck sensation (p = 0.010) and in improving cosmetic satisfaction (p = 0.036) than TLCIT. At 6-month follow-up, SOIT was feedback with better cosmetic satisfaction (p < 0.001) and a lower percent of abnormal neck sensation (p = 0.031) or movement (p = 0.005). Conclusion: Our study suggests that minimally invasive surgery using the SOI provides superior surgical and patient-related outcomes compared with surgery using a traditional low collar incision (TLCI) in patients with DTC.

The clinical impact of extrathyroidal extensions on prognoses in pediatric differentiated thyroid cancers.

BACKGROUND: The prognostic impact of extrathyroidal extensions (ETE) on clinical outcomes has not been well studied in pediatric thyroid cancers. The aim of this study was to analyze the clinicopathological characteristics and clinical outcomes according to the extent of ETE in pediatric and adolescent thyroid cancers. METHODS: This study retrospectively reviewed 89 papillary thyroid carcinoma (PTC) patients less than 19 years of age who underwent total thyroidectomy with central neck dissections (CND) between 1997 and 2018. We compared the clinicopathological features among three groups: no ETE, microscopic ETE, and gross ETE. RESULTS: The median follow-up time was 111 months. The mean age was 15.3 years and the mean tumor size was 2.4 cm. Tumor sizes larger than 2 cm (OR = 9.2, p = 0.001), exhibited bilaterality (OR = 4.3, p = 0.006), were an aggressive variant (OR = 5.8, p = 0.006), and exhibited central lymph node metastasis (OR = 1.3, p = 0.018), lateral lymph node metastasis (OR = 9.2, p = 0.001), recurrence (OR = 3.9, p = 0.038), and distant metastasis (OR = 4.4, p = 0.016) were associated with gross ETE. There was no remarkable difference in clinicopathological characteristics between the no ETE group and microscopic ETE group, except for aggressive variants (OR = 5.5, p = 0.008). There was a significant difference in recurrence-free survival (RFS) rates according to the extent of ETE (p = 0.025). Furthermore, the distant metastasis-free survival curve presented a significant difference among the three groups (p = 0.018). Both microscopic ETE and gross ETE were significantly associated with worse prognoses in pediatric thyroid cancers. CONCLUSIONS: We recommend that microscopic ETE should be included in the intermediate risk category and that gross ETE should be stratified in the high risk group in future revisions of ATA pediatric guidelines.

Actions of Thyroid Hormones on Thyroid Cancers.

L-Thyroxine (T4) is the principal ligand of the thyroid hormone analogue receptor on the extracellular domain of integrin αvß3. The integrin is overexpressed and activated in cancer cells, rapidly dividing endothelial cells, and platelets. The biologic result is that T4 at physiological concentration and without conversion to 3,3',5-triiodo-L-thyronine (T3) may stimulate cancer cell proliferation and cancer-relevant angiogenesis and platelet coagulation. Pro-thrombotic activity of T4 on platelets is postulated to support cancer-linked blood clotting and to contribute to tumor cell metastasis. We examine some of these findings as they may relate to cancers of the thyroid. Differentiated thyroid cancer cells respond to physiological levels of T4 with increased proliferation. Thus, the possibility exists that in patients with differentiated thyroid carcinomas in whom T4 administration and consequent endogenous thyrotropin suppression have failed to arrest the disease, T4 treatment may be stimulating tumor cell proliferation. In vitro studies have shown that tetraiodothyroacetic acid (tetrac), a derivative of T4, acts via the integrin to block T4 support of thyroid cancer and other solid tumor cells. Actions of T4 and tetrac or chemically modified tetrac modulate gene expression in thyroid cancer cells. T4 induces radioresistance via induction of a conformational change in the integrin in various cancer cells, although not yet established in thyroid cancer cells. The thyroid hormone receptor on integrin αvß3 mediates a number of actions of T4 on differentiated thyroid cancer cells that support the biology of the cancer. Additional studies are required to determine whether T4 acts on thyroid cancer cells.

Role and Extent of Neck Dissection for Neck Lymph Node Metastases in Differentiated Thyroid Cancers.

Differentiated thyroid cancers (DTC) consist of 95% of thyroid tumors and include papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and Hurthle cell thyroid cancer (HTC). Rates of lymph node metastases are different depending on histologic subtypes and <5% in FTC and between 5% and 13% in HTC. Lymph node metastasis is more frequent in PTC and while rate of clinical metastasis can be seen approximately 30% rate of routine micrometastasis can be seen up to 80%. Lymph node metastasis of DTC mostly develops first in the Level VI lymph nodes at the central compartment starting from the ipsilateral paratracheal lymph nodes and then spreading to the contralateral paratracheal lymph nodes. Spread to the Level VII is mostly after Level VI invasion. Subsequent spread is to the lateral neck compartments of Levels IV, III, IIA, and VB and sometimes to the Levels IIB and VA. Occasionally skip metastasis to the lateral neck compartments develop without spreading to the central compartments and this situation is more frequent in upper pole tumors. Although application of prophylactic central neck dissection (pCND) in DTC increases the rate of complication, due to its unclear effects on oncologic results and quality of life, the interest to the pCND is decreasing and debate on its surgical extent is increasing. pCND is not essential in DTC and characteristics of patient and tumor and experience of surgeon should be considered when deciding for pCND. Due to lower complication rate of one sided pCND compared to bilateral central neck dissection (CND), low possibility of contralateral central neck metastasis and low risk of recurrence, application of one-sided CND is logical. Although therapeutic CND (tCND) is the standart treatment when there is a clinically involved lymph node, extent of dissection is a matter of debate. A case-based decision for the extent of tCND can be made by considering patient and tumor characteristics and experience of the surgeon. Due to the higher complication risk of bilateral CND, unilateral tCND can be performed if there is no suspicious lymph node on the contralateral side and bilateral tCND can be applied when there is a suspicion for metastasis only on the contralateral side or there are features for risk of metastasis to the contralateral side. In patients with clinical central metastasis owing to intra-operative pathology results by frozen section procedure are compatible with post-operative pathology results, when there is a suspicion for contralateral metastasis, a decision for one- or two-sided dissection can be made using frozen section procedure. In DTC, it can be stated that there is a consensus in the literature about not performing prophylactic lateral neck dissection (LND), but performing therapeutic LND (tLND). In addition, there is a debate on the extent of tLND. In a meta-analysis about lateral metastasis, the rates of metastasis to the Levels IIA, IIB, III, IV, VA, and VB were 53.1%, 15.5%, 70.5%, 66.3%, 7.9%, and 21.5%, respectively. Ultrasonography (USG) is an effective procedure for detection of cervical nodal metastasis on lateral compartment. Pre-operative imaging with USG and/or combination with the fine needle aspiration biopsy (cytology/molecular test/Thyroglobulin test) can allow pre-operative detection and verification of lateral lymph node metastasis. Extent of tLND can be determined to minimize morbidity considering pre-operative USG findings, pre-operative tumor and clinical features of lateral metastasis. Especially in the presence of limited lateral metastases, limited selective LND such as Levels III, IV or Levels IIA, III, IV can be applied according to the patient. Levels IIB and VB should be added to the dissection in the presence of metastases in these regions. In cases that increase the risk of Level IIB involvement, such as presence of metastasis at Level IIA, extranodal tumor involvement, presence of multifocal tumor, and in cases that increase the risk of Level VB involvement such as macroscopic extranodal spread, and simultaneous metastases at Levels II, III, IV; Levels IIB and VB can be added to dissection material. Levels I and VA should be added to the dissection in the presence of clinically detected metastases.

Prognostic Factors in Patients with Differentiated Thyroid Cancers Metastatic to the Cervical Spine.

OBJECTIVES: The spine is the most common site of bone metastases in differentiated thyroid cancer (DTC). The role of surgery in the management of cervical spine (C-spine) metastases (CSpM) has not been adequately explored. METHODS: This is a retrospective cohort study at a tertiary referral center from 2002 to 2018. Inclusion criteria were pathologic diagnosis of DTC and imaging/pathologic diagnosis of CSpM. Statistical analysis utilized t tests for continuous variables and χ2 tests for categorical variables. Survival analysis was conducted using Kaplan-Meier curves with univariate and multivariate Cox regressions. RESULTS: Fifty patients with DTC and CSpM were identified. Of those, 16 underwent surgical resection of the C-spine, whereas 34 did not. The most common presenting symptom was neck pain (N = 37, 74%). Patients in the surgery group were more likely to report a subjective improvement of symptoms (P < .01) and to have local (P < .01) and systemic (P = .04) disease control. Five-year overall survival was 44.7% for the surgery group (95% confidence interval [CI]: 17.1-69.3) and 11.1% (95% CI: 2.1-28.8) for the nonsurgery group (P = .01). The strongest risk factor for improved overall survival after C-spine metastasis was local disease control at the C-spine (multivariate hazard ratio [HR] = 0.32, 95% CI: 0.12-0.85, P = .02). Surgical intervention was significantly associated with improved survival on both univariate (HR = 0. 35, 95% CI: 0.15-0.82, P = .02) and multivariate (HR = 0.37, 95% CI: 0.14-0.98, P = .04) analysis. CONCLUSION: Surgical management of CSpM in differentiated thyroid cancers is associated with significantly improved local disease control and overall survival. Referral to spine surgeons should be considered after diagnosis. LEVEL OF EVIDENCE: IV. Laryngoscope, 131:E1741-E1747, 2021.

Experiences of low iodine diets in the treatment of differentiated thyroid cancer with radioactive iodine ablation therapy.

BACKGROUND AND AIMS: International guidelines on the treatment of differentiated thyroid cancers (DTC) promote the use of low iodine diets (LID) prior to radioactive iodine remnant ablation (RIA), as high iodine status may interfere with radioiodine uptake. Most UK treatment centres adhere to these guidelines and advise people to consume a LID. There is limited research as to how people cope with the LID or its impact on daily life and wellbeing, and no studies have been conducted in the UK. This study explored peoples' views and experiences in relation to consuming a LID during treatment for DTC with RIA. METHODS: Twenty-eight semi-structured interviews were conducted with people from across three treatment centres where differing advice had been delivered regarding a LID. Interviews were recorded, transcribed verbatim and key themes were developed through inductive thematic analyses. RESULTS: Individuals advised to consume a LID believed that adhering to the diet would help their treatment. Most restricted their diets beyond what was recommended and there was confusion surrounding what they could eat as part of the diet. Food selection and preparation were important which included substitution of foods and ingredient checking. Being on the diet was considered to have both a physical and psychological impact. CONCLUSIONS: The findings of this study provide a qualitative insight into the lived experiences of people with DTC in relation to consuming a LID. The results have relevance for professionals providing dietary guidance at oncology centres treating patients with RIA therapy in the UK.

Impact of body mass index on survival outcome in patients with differentiated thyroid cancer / Impacto do índice de massa corporal sobre o desfecho de sobrevida em pacientes com câncer diferenciado de tireoide

Abstract Introduction Increased body mass index is known to be associated with the high prevalence of differentiated thyroid cancers; however data on its impact on survival outcome after thyroidectomy and adjuvant therapy is scanty. Objective We aimed to evaluate the impact of body mass index on overall survival and disease free survival rates in patients with differentiated thyroid cancers. Methods Between 2000 and 2011, 209 patients with differentiated thyroid cancers (papillary, follicular, hurthle cell) were treated with thyroidectomy followed by adjuvant radioactive iodine-131 therapy and thyroid-stimulating hormone suppression. Based on body mass index, patients were divided into five groups; (a) <18.5 kg/m2 (underweight); (b) 18.5-25 kg/m2 (normal weight); (c) 26-30 kg/m2 (overweight); (d) 31-40 kg/m2 (obese) and (e) >40 kg/m2 (morbid obese). Various demographic, clinical and treatment characteristics and related toxicity and outcomes (overall survival, and disease free survival) were analyzed and compared. Results Median follow up period was 5.2 years (0.6-10). Mean body mass index was 31.3 kg/m2 (17-72); body mass index 31-40 kg/m2 was predominant (89 patients, 42.6%) followed by 26-30 kg/m2 seen in 58 patients (27.8%). A total of 18 locoregional recurrences (8.6%) and 12 distant metastasis (5.7%) were seen. The 10 year disease free survival and overall survival rates were 83.1% and 58.0% respectively. No significant impact of body mass index on overall survival or disease free survival rates was found (p = 0.081). Similarly, multivariate analysis showed that body mass index was not an independent prognostic factor for overall survival and disease free survival. Conclusion Although body mass index can increase the risk of thyroid cancer, it has no impact on treatment outcome; however, further trials are warranted.

Resumo Introdução Sabe-se que o aumento do índice de massa corpórea está associado à alta prevalência de câncer diferenciado de tireoide; entretanto, os dados sobre seu impacto no desfecho de sobrevivência após tireoidectomia e terapia adjuvante são escassos. Objetivo Objetivou-se avaliar o impacto do índice de massa corpórea nas taxas de sobrevida global e sobrevida livre de doença em pacientes com câncer diferenciado de tireoide. Método Entre 2000 e 2011, 209 pacientes com câncer diferenciado de tireoide (papilar/folicular/de células de Hurthle) foram tratados através de tireoidectomia, seguida de tratamento com iodo radioativo-131 adjuvante e supressão de hormônio estimulante da tireoide. Com base no índice de massa corpórea, os pacientes foram divididos em cinco grupos; (a) < 18,5 kg/m2 (baixo peso); (b) 18,5-25 kg/m2 (peso normal); (c) 26-30 kg/m2 (sobrepeso); (d) 31-40 kg/m2 (obesos) e (e) > 40 kg/m2 (obesos mórbidos). Várias características demográficas, clínicas e de tratamento e toxicidade associada e desfechos (sobrevida global e sobrevida livre de doença) foram analisadas e comparadas. Resultados O período médio de acompanhamento foi de 5,2 anos (0,6-10). O índice de massa corpórea médio foi de 31,3 kg/m2 (17-72); o índice de massa corpórea de 31-40 kg/m2 foi predominante (89 pacientes, 42,6%), seguido por 26-30 kg/m2, observado em 58 pacientes (27,8%). Observaram-se 18 recidivas locorregionais (8,6%) e 12 metástases distantes (5,7%). As taxas de sobrevida livre de doença e sobrevida global de 10 anos foram de 83,1% e 58,0%, respectivamente. Não foi encontrado impacto significativo do índice de massa corpórea nas taxas de sobrevida global ou sobrevida livre de doença (p = 0,081). Da mesma forma, a análise multivariada mostrou que o índice de massa corpórea não foi um fator prognóstico independente para sobrevida global e sobrevida livre de doença. Conclusão Embora o índice de massa corpórea possa aumentar o risco de câncer de tireoide, ele não tem impacto no resultado do tratamento; contudo, outros estudos são necessários.

Optimization of the risk-benefit ratio of differentiated thyroid cancer treatment.

The vast majority of differentiated thyroid cancers (DTC) are characterized by an innocuous nature, excellent patient survival, and limited treatment requirement. However, a significant proportion of affected patients is prone to receiving overtreatment, due to undertreatment concerns associated with the difficulty to differentiate them from a small minority affected by aggressive DTC. Identification of prognostic factors and development of staging systems has helped to reduce the proportion of overtreatment in DTC. However, the absolute number of overtreated patients continues to increase, as a result of an on-going incidence surge in early DTC associated with the increased application and sensitivity of modern diagnostic tools. In the present paper, we describe how DTC treatment can be optimized by thoughtful evidence-based balancing of oncologic safety against treatment associated morbidity.

Impact of body mass index on survival outcome in patients with differentiated thyroid cancer.

INTRODUCTION: Increased body mass index is known to be associated with the high prevalence of differentiated thyroid cancers; however data on its impact on survival outcome after thyroidectomy and adjuvant therapy is scanty. OBJECTIVE: We aimed to evaluate the impact of body mass index on overall survival and disease free survival rates in patients with differentiated thyroid cancers. METHODS: Between 2000 and 2011, 209 patients with differentiated thyroid cancers (papillary, follicular, hurthle cell) were treated with thyroidectomy followed by adjuvant radioactive iodine-131 therapy and thyroid-stimulating hormone suppression. Based on body mass index, patients were divided into five groups; (a) <18.5kg/m2 (underweight); (b) 18.5-25kg/m2 (normal weight); (c) 26-30kg/m2 (overweight); (d) 31-40kg/m2 (obese) and (e) >40kg/m2 (morbid obese). Various demographic, clinical and treatment characteristics and related toxicity and outcomes (overall survival, and disease free survival) were analyzed and compared. RESULTS: Median follow up period was 5.2years (0.6-10). Mean body mass index was 31.3kg/m2 (17-72); body mass index 31-40kg/m2 was predominant (89 patients, 42.6%) followed by 26-30kg/m2 seen in 58 patients (27.8%). A total of 18 locoregional recurrences (8.6%) and 12 distant metastasis (5.7%) were seen. The 10 year disease free survival and overall survival rates were 83.1% and 58.0% respectively. No significant impact of body mass index on overall survival or disease free survival rates was found (p=0.081). Similarly, multivariate analysis showed that body mass index was not an independent prognostic factor for overall survival and disease free survival. CONCLUSION: Although body mass index can increase the risk of thyroid cancer, it has no impact on treatment outcome; however, further trials are warranted.

Approach to thyroid carcinoma in pregnancy.

Thyroid carcinoma is the first cancer found in general population and the second diagnosed during pregnancy following the breast one. Diagnostic and therapeutic approaches to thyroid malignancy in pregnant women pose several and serious issues to the physicians. Even if there is no consensus about the surgical treatment of thyroid carcinomas during pregnancy, a large number of women undergo surgery over the world. The best surgical and anesthesiological treatment should be chosen after reaching a consensus between surgeons, anesthesiologists, obstetrics, and the patients. From 2000 to 2016, 18 pregnant patients underwent thyroidectomy under local anesthesia (cervical plexus block) combined with conscious sedation using benzodiazepines and opiates with ultrashort duration of action. Our 15-year experience on the thyroidectomies performed using the cervical plexus block combined with conscious sedation confirms that this combined technique offers a safe chance to defeat cancer also during pregnancy. Application of hypnosis could be an interesting alternative approach to pharmacological sedation in patients who would avoid intravenous drugs.

Recent Advances in Our Understanding of Well-Differentiated Thyroid Cancers.

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Comparative clinicopathological and outcome analysis of differentiated thyroid cancer in Saudi patients aged below 60 years and above 60 years.

INTRODUCTION: The aim of this study was to evaluate the treatment outcomes of differentiated thyroid cancer in Saudi patients aged above 60 years. MATERIALS AND METHODS: Comparative analysis was performed in 252 patients aged 46-60 years (Group A) and 118 patients aged above 60 years (Group B), who had thyroidectomy, radioactive iodine-131, and thyroid-stimulating hormone suppression therapy between July 2000 and December 2012. Different clinicopathological features, treatment, complications, disease-free survival, and overall survival rates were compared. RESULTS: Mean age of patients in Group A was 51.9 years (range: 46-60), and mean age of those in Group B was 68.6 years (range: 62-97). Group B patients had higher positive lymph nodes (43.2%), P=0.011. The frequency of extrathyroidal extension, multifocality, and lymphovascular space invasion was seen more in Group B than in Group A. Postsurgical complications (permanent hypoparathyroidism, bleeding, and wound infections) were also seen more in Group B (P=0.043, P=0.011, and P=0.021, respectively). Group B patients experienced more locoregional recurrences (11.0%, P=0.025); similarly, more distant metastases were observed in Group B (15.3%, P=0.003). The 10-year disease-free survival rates were 87.6% in Group A and 70.8% in Group B (P<0.0001). CONCLUSION: Differentiated thyroid cancer in patients aged above 60 years are more aggressive biologically and associated with a worse prognosis, and the morbidity is significantly high as compared to patients aged below 60 years.

Trends and Predictors of Chemotherapy Use among Thyroid Cancer Patients in the National Cancer Database (2004-2013).

BACKGROUND/AIM: Beginning in 2011, the Food and Drug Administration (FDA) approved the use of multikinase inhibitors (MKIs) for medullary thyroid cancers (MTCs), and in 2013 MKIs were approved for metastatic differentiated thyroid cancers (DTCs). However, little is known about the use of chemotherapy in thyroid cancer patients. Thus, the goal of our study was to describe patterns of chemotherapy use, including MKIs, among DTC and MTC patients in the National Cancer Database (NCDB). METHODS: Chemotherapy use, along with other treatment types (surgery and radiation), was assessed between 2004 and 2013. The primary predictor was the year of diagnosis (2004-2010 and 2011-2013), based on the FDA's approval of chemotherapy for MTC (2011). Baseline use of MKIs in DTCs in 2013 was also examined. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% CI of receipt of chemotherapy. RESULTS: Overall, 199,654 patients were included in our analytic sample with 194,667 nonmetastatic DTCs, 1,633 metastatic DTCs, and 3,354 MTCs. Among MTCs, chemotherapy use significantly increased from 3.1% in 2004-2010 to 5.0% in 2011-2013 (p = 0.018) in unadjusted and adjusted (OR = 1.54, 95% CI: 1.00, 2.36) analyses. In metastatic DTCs, 4.9% of patients received chemotherapy in 2013, which was not significantly higher than in previous years (p = 0.755). CONCLUSIONS: Overall, chemotherapy use among MTCs increased marginally following the FDA's approval of MKIs in 2011, although their use remains very low. MKIs were infrequently used in metastatic DTCs in 2013. Future studies examining patterns of chemotherapy in thyroid cancer patients are warranted.

[Advances in thyroglobulin assays and their impact on the management of differentiated thyroid cancers]. / Avancées dans les dosages de thyroglobuline et leur impact dans la prise en charge des cancers différenciés de la thyroïde.

Thyroglobulin (Tg) is a high molecular weight glycoprotein located mainly in thyroid follicles, where thyroid hormones are synthesized and stored. In patients with differentiated thyroid cancer of follicular origin, serum Tg levels become undetectable following total thyroidectomy and iodine-131 remnant ablation. It is a key biomarker to follow-up patients with differentiated thyroid cancer, in combination with neck ultrasound monitoring. The measurement of Tg in the wash-out of the needle used for fine needle aspiration biopsy is a valuable aid to the diagnosis of lymph node metastasis. The presence of anti-thyroglobulin antibodies affects reliability of Tg results measured in serum or plasma. Systematic investigation of such antibodies is required to validate any Tg assay. Elevated or rising levels of anti-thyroglobulin antibodies can in turn be used as a surrogate tumor marker of thyroid cancer. The development of second-generation Tg assay (automated, highly sensitive) has enabled significant advances in the management of differentiated thyroid cancer: early detection of persistent or recurrent disease and follow-up care simplified in low-risk patients. Testing of serum Tg can also be useful in evaluating other clinical situations such as congenital hypothyroidism, endemic goiter and thyrotoxicosis factitia.

Nasolacrimal duct obstruction following radioactive iodine 131 therapy in differentiated thyroid cancers: review of 19 cases.

BACKGROUND: Radioactive iodine 131 ((131)I) therapy has long been used in the treatment of differentiated thyroid cancers (DTC). While salivary and lacrimal glandular complications secondary to (131)I therapy are well documented, there is little in the literature addressing nasolacrimal duct obstruction (NLDO). We aimed to evaluate the frequency of (131)I therapy-acquired NLDO, its correlation to (131)I therapy doses, and the surgical treatment outcome of this rare side effect. METHODS: From 2000-2012, a retrospective review of 864 among 1,192 patients with confirmed DTC who were treated with (131)I therapy was performed to examine the frequency of NLDO, its causative factors, as well as imaging, surgical intervention, and outcomes. RESULTS: Nineteen (2.2%) patients were identified with NLDO. The mean age was 51.9±10.5 years (range: 39-72 years). Fifteen (78.9%) were female and four were male (21.1%). The mean individual (131)I doses were 311.1±169.3 millicurie (mCi) (range: 150-600 mCi). The mean duration between the date of (131)I therapy and the occurrence of NLDO was 11.6±4.1 months (range: 6.5-20). Fourteen (73.7%) patients had bilateral epiphora. Computed tomography dacryography allowed for the detection of all NLDO. Eighteen (94.7%) patients underwent dacryocystorhinostomy. Complete recovery was obtained in 14 (73.7%) patients. Age >45 years and (131)I therapy doses >150 mCi were significantly correlated with NLDO (P=0.02 and P=0.03, respectively). CONCLUSION: NLDO is an underestimated complication of (131)I therapy in DTC patients. Clinicians should be aware of this rare complication for prompt intervention.