Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm.

PURPOSE: Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm. METHODS: A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma. RESULTS: A total of 1313 patients were included, of whom 426 (32 %) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67 %) papillary thyroid carcinomas (PTC), 124 (30 %) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1 %) follicular thyroid carcinomas (FTC), and 3 (1 %) Hürthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82 % were ≤10 mm and of those 99 % were PTC or FvPTC. Even if the primary tumor was a FTC or HTC, the contralateral carcinoma was (Fv)PTC in 92 % of cases. CONCLUSIONS: This international multicenter study performed on patients with DTC larger than 1 cm shows that contralateral carcinomas occur in one third of patients and, independently of primary tumor subtype, predominantly consist of microPTC.

Risk factors and outcomes of blood transfusions in adrenalectomy.

BACKGROUND: Blood transfusion has been shown to be associated with adverse long-term and short-term outcomes. We sought to evaluate the preoperative risk factors associated with blood transfusion and its effects on postoperative outcomes after adrenalectomy. METHODS: We performed a retrospective analysis of 4735 adrenalectomies (3664 laparoscopic and 1071 open) from 2005-2012 using the National Surgical Quality Improvement Program database. Data on preoperative risk factors and postoperative morbidity and mortality were evaluated. RESULTS: Median age and body mass index were 54 y and 29.3 kg/m(2), respectively. Most patients were female (60.0%). Of the total, 60.6% patients had American Society of Anesthesiologists score ≥3. On multivariate analysis, increasing age (odds ratio [OR] = 1.02, P < 0.001), open adrenalectomy (OR = 14.0, P < 0.001), preoperative hematocrit <38% (OR = 2.96, P < 0.001), and operative time >150 min (OR: 3.69, P < 0.001) were associated with an increased need for intraoperative blood transfusions. The need for intraoperative blood transfusions was an independent predictor of postoperative complications including mortality (OR = 12.7, P < 0.001), overall morbidity (OR = 3.2, P < 0.001), serious morbidity (OR = 3.8, P < 0.001), wound complication (OR = 2.1, P = 0.006), cardiopulmonary complication (OR = 3.6, P < 0.001), septic complication (OR = 2.5, P = 0.007), reoperation (OR = 3.6, P < 0.001), and prolonged length of stay (OR = 4.3, P < 0.001). There was an independent and incremental increase (10%-20%) in the risk of morbidity and mortality with each unit of blood transfused (P < 0.01). CONCLUSIONS: Age, open surgery, preoperative anemia, American Society of Anesthesiologists score, and prolonged operative time are associated with an increased need for blood transfusions in laparoscopic and open adrenalectomy. Intraoperative transfusion was independently and incrementally associated with significant morbidity and mortality after laparoscopic and open adrenalectomy.

Resident participation and postoperative outcomes in adrenal surgery.

BACKGROUND: The changing paradigm of surgical residency training has raised concerns about the effects on the quality of training. The purpose of this study is to identify if resident participation in laparoscopic adrenalectomy (LA) and open adrenalectomy (OA) cases is associated with deleterious outcomes. MATERIALS AND METHODS: This is a retrospective study using the American College of Surgeons National Surgical Quality Improvement Program database. Data from patients undergoing LA and OA from 2005 to 2010 were queried. Preoperative variables as well as intra- and post-operative outcomes for each procedure were evaluated. Multivariate logistic regression was used to analyze if resident participation was associated with significant differences in outcomes, compared with no resident participation. Subset analysis was done to determine possible differences in outcomes based on the level of resident participating, divided into junior (Post Graduate Year [PGY]1-3), senior (PGY4-5), or fellow (≥PGY6) levels. RESULTS: A total of 3219 adrenalectomies were performed. Of these, 735 (22.8%) were OAs and 2484 (77.2%) were LAs. Residents were involved in 2582 (80.2%) surgeries, which comprised 1985 (76.9%) LAs and 597 (23.1%) OAs. Senior residents or fellows performed majority of the cases (85.2%). Mean operative time was significantly higher with resident participation in LA (P < 0.0001) and OA group (P < 0.0001). On multivariate analysis, resident participation was not associated with significant differences in the operative outcomes of 30-d mortality or postoperative complications after laparoscopic or OA. CONCLUSIONS: Although resident participation does increase operative time in LA and OA, this does not appear to be clinically significant and does not result in adverse patient outcomes.

Recent advances in the surgical treatment of differentiated thyroid cancer: a comprehensive review.

Differentiated thyroid cancers have become one of the fastest growing malignancies in the world. While surgery has remained the cornerstone of management of these tumors, the surgical approach has seen numerous innovations over the past few decades. The use of video-assistance and robotics has revolutionized thyroid surgery. This paper provides a comprehensive evaluation of the different approaches to thyroid surgery, the utility of prophylactic and therapeutic lymph node dissection, and evidence-based guidelines in the treatment of differentiated thyroid cancers. Minimally invasive video-ssisted thyroidectomy is both safe and effective in the hands of the trained surgeon and, in selected patient populations, has comparative perioperative morbidity and better cosmesis as compared to conventional open thyroidectomy. It is universally accepted that therapeutic central lymph node dissection should be performed when metastatic lymph nodes are identified on physical exam, ultrasound, or intraoperatively. In the absence of overt nodal metastasis, the role of elective prophylactic central lymph node dissection remains a matter of debate and prospective, randomized studies are warranted to evaluate the utility of this procedure.

MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer.

BACKGROUND: Approximately 30% of fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy. METHODS: A miRNA array was used to identify differentially expressed genes (5-fold higher or lower) in pooled normal, malignant, and benign thyroid tissue samples. Real-time quantitative polymerase chain reaction was used to confirm miRNA array expression data in 104 tissue samples (7 normal thyroid, 14 hyperplastic nodule, 12 follicular variant of papillary thyroid cancer, 8 papillary thyroid cancer, 15 follicular adenoma, 12 follicular carcinoma, 12 Hurthle cell adenoma, 20 Hurthle cell carcinoma, and 4 anaplastic carcinoma cases), and 125 indeterminate clinical FNA samples. The diagnostic accuracy of differentially expressed genes was determined by analyzing receiver operating characteristics. RESULTS: Ten miRNAs showed >5-fold expression difference between benign and malignant thyroid neoplasms on miRNA array analysis. Four of the 10 miRNAs were validated to be significantly differentially expressed between benign and malignant thyroid neoplasms by quantitative polymerase chain reaction (P < .002): miR-100, miR-125b, miR-138, and miR-768-3p were overexpressed in malignant samples of follicular origin (P < .001), and in Hurthle cell carcinoma samples alone (P < .01). Only miR-125b was significantly overexpressed in follicular carcinoma samples (P < .05). The accuracy for distinguishing benign from malignant thyroid neoplasms was 79% overall, 98% for Hurthle cell neoplasms, and 71% for follicular neoplasms. The miR-138 was overexpressed in the FNA samples (P = .04) that were malignant on final pathology with an accuracy of 75%. CONCLUSIONS: MicroRNA expression differs for normal, benign, and malignant thyroid tissue. Expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy.

Fluorodeoxyglucose-positron emission tomography scan-positive recurrent papillary thyroid cancer and the prognosis and implications for surgical management.

BACKGROUND: To compare outcomes for patients with recurrent or persistent papillary thyroid cancer (PTC) who had metastatic tumors that were fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative, and to determine whether the FDG-PET scan findings changed the outcome of medical and surgical management. METHODS: From a prospective thyroid cancer database, we retrospectively identified patients with recurrent or persistent PTC and reviewed data on demographics, initial stage, location and extent of persistent or recurrent disease, clinical management, disease-free survival and outcome. We further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT scan and whole-body radioactive iodine scans and categorized them by whether they had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The medical and surgical treatments and outcome of these patients were compared. RESULTS: Between 1984 and 2008, 41 of 141 patients who had recurrent or persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22 patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative lesions, and two had indeterminate lesions. Most PET-positive lesions were located in the neck (55%). Patients who had a PET-positive lesion had a significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22 vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who underwent surgical resection of their PET-positive lesions, loco-regional control was obtained without evidence of residual disease. CONCLUSION: Patients with recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis. In some patients loco-regional control can be obtained without evidence of residual disease by reoperation if the lesion is localized in the neck or mediastinum.

Adherence to a standardized infection reduction bundle decreases surgical site infections after colon surgery: a retrospective cohort study on 526 patients.

BACKGROUND: Colon surgical site infections (SSI) are detrimental to patient safety and wellbeing. To achieve clinical excellence, our hospital set to improve patient safety for those undergoing colon surgery. Our goal was to implement a perioperative SSI prevention bundle for all colon surgeries to reduce colon surgery SSI rates. METHODS: This retrospective cohort study evaluated the impact of implementing a perioperative SSI prevention bundle in patients undergoing colon surgery at Banner University Medical Center - Tucson. We compared SSI rates between the Pre- (1/1/2016 to 12/31/2016) and post-bundle (1/1/2017 to 12/31/2017) cohorts using a chi-square test. RESULTS: In total, we included 526 consecutive patients undergoing colon surgery in our study cohort; 277 pre-bundle and 249 post-bundle implementation. The unadjusted SSI rates were 8.7 % and 1.2 %, pre- and post-bundle, respectively. Our CMS reportable standard infection rate decreased by 85.4 % from 3.08 to 0.45 after implementing our SSI prevention bundle. CONCLUSIONS: Implementing a standardized colon SSI prevention bundle reduces the overall 30-day colon SSI rates and national standardized infection rates. We recommend implementing colon SSI reduction bundles to optimize patient safety and minimize colon surgical site infections.

Diagnostic markers and prognostic factors in thyroid cancer.

There has been considerable progress identifying biomarkers in thyroid tumors that improve the accuracy of fine-needle aspiration biopsy and also help predict tumor aggressiveness or behavior. In this review we address both the clinical potential of molecular biomarkers and their usefulness, based on the most recent literature. We describe the current best clinical staging systems and the common somatic mutations in thyroid cancer. The BRAF mutation is the most common mutation in papillary thyroid cancer and has recently been reported to be associated with disease aggressiveness; it is also an independent predictor of tumor behavior. Combined testing of RET/PTC, NTRK, RAS and PAX8-PPARgamma, which are mutually exclusive mutations, helps improve the accuracy of fine-needle aspiration biopsy. Gene-expression profiling studies have identified a variety of potential molecular markers to help distinguish benign from malignant thyroid neoplasms. Expression analysis of differentially expressed microRNAs also appears to be a promising diagnostic approach for distinguishing benign from malignant thyroid neoplasm. It is especially useful for indeterminate nodules by fine-needle aspiration biopsy.

A comparison of carotid artery stenting with neuroprotection versus carotid endarterectomy under local anesthesia.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce the risk of stroke in patients with high-grade carotid artery stenosis. Despite the known impact of type of anesthesia on outcome after CEA, none of the current studies comparing CEA with CAS addresses the effect of anesthetic choice on perioperative events. In this study, we compare our results of distally protected CAS versus CEA under local anesthesia. METHODS: Clinical data of 345 patients who underwent 372 procedures for carotid artery occlusive disease over a 36-month were retrospectively collected for this analysis. Distal embolic protection was used in CAS procedures. All procedures, both CEA (n = 221, 59%) and CAS (N = 152, 41%), were performed under local anesthesia. The primary outcome measure was aggregate 30-day major ipsilateral stroke and/or death. Follow-up serial Duplex ultrasound examinations were performed. RESULTS: Both patient cohorts were similar in terms of demographic and risk factors, with the exception of a higher incidence of coronary artery disease in the CAS group (59% versus 30%, P <.05). The 30-day stroke and death rates were 3.2% (CAS) and 3.7% (CEA) (P = not significant). Cranial nerve injury only occurred in the CEA patients (2.3%). Perioperative hemodynamic instability was more common among patients in the CAS group (11.9% versus 4.1%, P <.05). CONCLUSIONS: Percutaneous carotid stenting with neuroprotection provides comparable clinical success to CEA performed under local anesthetic. Further studies are warranted to validate the long-term efficacy of CAS and to elucidate patient selection criteria for endovascular carotid revascularization.

Anastomotic strategies to improve hemodialysis access patency--a review.

The number of patients with end-stage renal disease (ESRD) who require maintenance hemodialysis has risen sharply in the past 2 decades. It is estimated that more than 60% of all patients with ESRD who require chronic hemodialysis are accessed through an arteriovenous fistula (AVF) or graft (AVG), and the incidence is increasing at a rate of 2% to 4% per year. The long-term patency rate of an upper extremity AVF or AVG for hemodialysis access remains suboptimal owing in part to progressive stenosis at the venous anastomosis. This article reviews the causative factors of dialysis access-related anastomotic stenosis, or intimal hyperplasia. This article also reviews the clinical experience of various anastomotic strategies to ameliorate the hemodynamic environment in an effort to improve the clinical outcome of hemodialysis access. These strategies include the use of (1) vein cuff at the expanded polytetrafluoroethylene (ePTFE)-venous anastomosis of AVG, (2) cuffed ePTFE dialysis AVG, and (3) anastomotic devices that create an interrupted anastomosis with staples or clips.

Risk Factors for Decreased Quality of Life in Thyroid Cancer Survivors: Initial Findings from the North American Thyroid Cancer Survivorship Study.

BACKGROUND: The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. METHODS: Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. RESULTS: A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. CONCLUSION: Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing.

Malignant phyllodes tumor of the breast: review of the literature and case report of stromal overgrowth.

Cystosarcoma phyllodes constitutes only 0.3-0.9% of all breast tumors. The term "sarcoma" was initially used because of its fleshy appearance, a more modern term is Phyllodes tumor (PT). The behavior of PT constitutes a spectrum from benign and locally recurrent to malignant and metastatic. In a general surgical series, 6.2% of the tumors were malignant. The microscopic appearance of PT is that of epithelial elements and connective tissue stroma. Malignancy is determined by characteristics of the stroma. The metastatic spread of malignant PT is mainly hematogenous to lung, with infrequent lymphatic involvement. Wide local excision with 2 cm margins is the treatment of choice. In 20% of both benign and malignant cases, PT will locally recur. There is no proven benefit of radiation or chemotherapy, although radiotherapy may be useful in selected cases. We present a case of a sarcomatous overgrowth in a malignant phyllodes tumor involving multiple histologic types.

The impact of anesthetic modality on the outcome of carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with high-grade carotid artery stenosis. This study evaluates the clinical outcome of CEA performed under local anesthesia (LA) versus general anesthesia (GA). METHODS: Clinical variables and treatment outcomes were analyzed in 548 CEAs performed under either LA or GA during a 30-month period. Factors associated with morbidity were also analyzed. RESULTS: A total of 263 CEAs under LA and 285 CEA under GA were analyzed. The LA group was associated with a lower incidence of shunt placement, operative time, and perioperative hemodynamic instability compared to the GA group. No differences in neurologic complications or mortality were found between the 2 groups. Hyperlipidemia was a risk factor for postoperative morbidity in both the LA and GA groups, while age greater than 75 years was associated with increased overall morbidity in the GA group but not the LA group. CONCLUSIONS: This study demonstrates that increased age is associated with increased morbidity in CEA under GA, while hyperlipidemia is associated with increased morbidity in CEA regardless of the anesthetic choice.

Comprehensive literature review: recent advances in diagnosing and managing patients with poorly differentiated thyroid carcinoma.

Poorly differentiated thyroid carcinomas are a rare form of thyroid carcinomas; they display an intermediate behavior between well-differentiated and anaplastic thyroid carcinomas. PDTCs are more aggressive than the well-differentiated, but less aggressive than the undifferentiated or anaplastic, forms. No clinical features can accurately diagnose poorly differentiated thyroid carcinomas. Thus, the results of histocytology, immunohistochemistry, and molecular genetics tests aid in diagnosis. Given the aggressiveness of poorly differentiated thyroid carcinomas and the poor survival rates in patients who undergo surgery alone, a multimodality treatment approach is required. We conducted a comprehensive review of the current diagnostic and therapeutic tools in the management of patients with poorly differentiated thyroid carcinomas.

Laterality of central venous sampling: lack of effect on the accuracy of intraoperative parathyroid hormone monitoring.

BACKGROUND: The purpose of this study was to determine if laterality of internal jugular vein (IJV) sampling affects the accuracy of intraoperative parathyroid hormone (PTH) monitoring during parathyroidectomy for primary hyperparathyroidism. METHODS: In this study, 109 patients underwent parathyroidectomy (82 with unilateral disease, 27 with multigland disease). PTH samples were taken from both the left and the right IJV at these time points: preincision (baseline) and then at 5, 10, and, in selected patients, 20 minutes after excision. The Miami criterion was used to determine operative success. RESULTS: In all 109 patients combined, the mean decreases in intraoperative PTH levels were 73.8 ± 22.2% for the left IJV and 71.9 ± 23.0% for the right IJV (P = .22). The Miami criterion was met in 105 patients: in 100 (95%) left IJV samples and 99 (94%) right IJV samples (P = 1.00). CONCLUSIONS: No difference was found in the accuracy of intraoperative PTH monitoring between patients' left and right IJV samples. Central venous laterality did not affect fulfillment of the Miami criterion.

Regional differences in thyroid cancer presentation and survival: a SEER study.

OBJECTIVE: The incidence of thyroid cancer has been steadily increasing. Several studies have identified gender and racial/ethnic differences in the incidence and prognosis of thyroid cancer. In this study, we sought to determine if the stage of presentation and survival rate of patients with thyroid cancer in the United States is affected by geographic region. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 100,404 patients diagnosed with thyroid cancer from 1973 through 2009. We assessed historical stage of diagnosis and cancer-free survival rate according to geographic region. To compare stages of diagnosis, we used multinomial logistic regression. To compare survival rates, we used Cox proportional hazards regression. Models were adjusted for age, year of diagnosis, cancer type, registry site, race/ethnicity, and stage. RESULTS: Of 100,404 patients, 52,902 (52.7%) were from the West, 17,915 (17.8%) from the East, 15,302 (15.2%) from the South, and 14,285 (14.2%) from the Midwest. Overall, most patients presented with localized disease. Those from the West had a higher risk of presenting with regional and distant metastases. When we double-stratified by cancer subtype and racial group, we found no significant associations between geographic region and cancer-free survival rate. CONCLUSION: The presentation stage and survival rate of patients with thyroid cancer differs by geographic region, but not within separate racial/ethnic groups.

Hemeoxygenase-1 mediated hypercoagulability in a patient with thyroid cancer.

Thyroid cancers can cause significant regional thrombotic morbidity and mortality. Of interest, thyroid cancer cell lines can have upregulation of the carbon monoxide-producing enzyme, hemeoxygenase-1. Carbon monoxide has been demonstrated to markedly enhance plasmatic coagulation in vitro and in vivo via enhancement of fibrinogen's substrate properties by binding to a fibrinogen-associated heme group(s). We present a patient undergoing removal of a malignant thyroid tumour who was serendipitously found to have abnormally increased carboxyhaemoglobin concentration (2.4%) and plasmatic hypercoagulability with a carbon monoxide-mediated clot strength as determined by a thrombelastographic method. This initial observation serves as a rationale to further investigate the role played by hemeoxygenase-1 upregulation in the setting of cancers associated with increased endogenous carbon monoxide production.

A multi-institutional international study of risk factors for hematoma after thyroidectomy.

BACKGROUND: Cervical hematoma can be a potentially fatal complication after thyroidectomy, but its risk factors and timing remain poorly understood. METHODS: We conducted a retrospective, case-control study identifying 207 patients from 15 institutions in 3 countries who developed a hematoma requiring return to the operating room (OR) after thyroidectomy. RESULTS: Forty-seven percent of hematoma patients returned to the OR within 6 hours and 79% within 24 hours of their thyroidectomy. On univariate analysis, hematoma patients were older, more likely to be male, smokers, on active antiplatelet/anticoagulation medications, have Graves' disease, a bilateral thyroidectomy, a drain placed, a concurrent parathyroidectomy, and benign pathology. Hematoma patients also had more blood loss, larger thyroids, lower temperatures, and higher blood pressures postoperatively. On multivariate analysis, independent associations with hematoma were use of a drain (odds ratio, 2.79), Graves' disease (odds ratio, 2.43), benign pathology (odds ratio, 2.22), antiplatelet/anticoagulation medications (odds ratio, 2.12), use of a hemostatic agent (odds ratio, 1.97), and increased thyroid mass (odds ratio, 1.01). CONCLUSION: A significant number of patients with a postoperative hematoma present >6 hours after thyroidectomy. Hematoma is associated with patients who have a drain or hemostatic agent, have Graves' disease, are actively using antiplatelet/anticoagulation medications or have large thyroids. Surgeons should consider these factors when individualizing patient disposition after thyroidectomy.

New insight into the treatment of advanced differentiated thyroid cancer.

The vast majority of patients with differentiated thyroid cancer (DTC) are treated successfully with surgery and radioactive iodine ablation, yet the treatment of advanced cases is frustrating and largely ineffective. Systemic treatment with conventional cytotoxic chemotherapy is basically ineffective in most patients with advanced DTC. However, a better understanding of the genetics and biologic basis of thyroid cancers has generated opportunities for innovative therapeutic modalities, resulting in several clinical trials. We aim to delineate the latest knowledge regarding the biologic characteristics of DTC and to describe the available data related to novel targeted therapies that have demonstrated clinical effectiveness.