Multi-targeted approach in the treatment of thyroid cancer

While accounting for only 1% of solid organ malignancies (9% in women), thyroid carcinoma is the most common malignancy of the endocrine system. Although most patients have a favorable prognosis, over 1,500 people will die from thyroid carcinoma each year. The spectrum of disease types range from papillary thyroid cancer, which is a well-differentiated indolent tumor, to anaplastic carcinoma, a poorly differentiated fulminant cancer. With advances in diagnostic methods, surgical techniques, and clinical care of patients with thyroid carcinoma, the current management of thyroid cancer demands a multidisciplinary approach. The majority of patients with well-differentiated thyroid carcinoma of follicular cell origin are cured with adequate surgical management; however, some thyroid malignancies such as medullary thyroid carcinoma (MTC) or poorly differentiated thyroid carcinomas frequently metastasize, precluding patients from a curative resection. As such, novel palliative and therapeutic strategies are needed for this patient population. Here, we explore the current management of thyroid carcinoma, including surgical management of the primary tumor, lymph node disease, and locoregional recurrence. Likewise, we explore the application of current molecular techniques, reviewing nearly two decades of data that have begun to elucidate critical genetic pathways and therapeutic drug targets which may be important in specific thyroid tumor types

Medullary Thyroid Carcinoma: Targeted Therapies and Future Directions

Medullary thyroid cancer (MTC) is a rare neuroendocrine neoplasm that accounts for approximately 5% of all thyroid malignancies. The natural history of MTC is characterized by early lymph node and distant metastases, making complete surgical cure often impossible. Conventional chemotherapy and external beam radiation have been largely ineffective in altering the natural history of MTC. Therefore, there is a great need to develop novel therapeutic strategies to affect symptom control and reduce tumor burden in patients with widely disseminated disease. Here, we review several pathways which have been shown to be vital in MTC tumorigenesis and focus on the pathways of interest for which targeted drug therapies are currently being developed

American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma

Background: The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). Methods and Results: We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. Conclusion: Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98487/1/thy%2E2011%2E0317.pd

S\uedndrome de Cushing subcl\uednico en incidentalomas suprarrenales

Hasta un 20% de los pacientes con incidentaloma (tumor detectado de manera incidental o accidental) suprarrenal tiene una producci\uf3n de cortisol anormal y se puede clasificar como con s\uedndrome de Cushing subcl\uednico. Aunque estos tumores no secretan suficiente cortisol para conducir a la aparici\uf3n de un s\uedndrome de Cushing franco, probablemente s\ued participan como elemento colaborador en el desarrollo de hipertensi\uf3n, diabetes, osteoporosis y obesidad. Los estudios indican que muchos de estos problemas pueden ser contrarrestados con el tratamiento quir\ufargico. Adem\ue1s, cuando este diagn\uf3stico no es buscado antes de realizar una adrenalectom\ueda para un incidentaloma, el paciente puede presentar insuficiencia suprarrenal posoperatoria profunda

Success in Academic Surgery: Developing a Career in Surgical Education

XIII, 152 p. 8 illus., 7 illus. in color.online r

Hypoparathyroidism after total thyroidectomy: incidence and resolution

BackgroundParathyroid hormone (PTH) levels are often measured after thyroid surgery and are used to detect patients at risk for postoperative hypoparathyroidism. However, there is a lack of consensus in the literature about how to define the recovery of parathyroid gland function and when to classify hypoparathyroidism as permanent. The goals of this study were to determine the incidence of low postoperative PTH in total thyroidectomy patients and to monitor their time course to recovery of parathyroid gland function.MethodsWe identified 1054 consecutive patients who underwent a total or completion thyroidectomy from January, 2006-December, 2013. Low PTH was defined as a PTH measurement <10 pg/mL immediately after surgery. Patients were considered to be permanently hypoparathyroid if they had not recovered within 1 y. Recovery of parathyroid gland function was defined as PTH ≥10 pg/mL and no need for therapeutic calcium or activated vitamin D (calcitriol) supplementation to prevent hypocalcemic symptoms.ResultsOf 1054 total thyroidectomy patients, 189 (18%) had a postoperative PTH <10 pg/mL. Of those 189 patients, 132 (70%) showed resolution within 2 mo of surgery. Notably, 9 (5%) resolved between 6 and 12 mo. At 1 y, 20 (1.9%) were considered to have permanent hypoparathyroidism. Surprisingly, 50% of those patients had recovery of PTH levels yet still required supplementation to avoid symptoms.ConclusionsMost patients with a low postoperative PTH recover function quickly, but it can take up to 1 y for full resolution. Hypoparathyroidism needs to be defined not only by PTH levels but also by medication requirements

Thyroidectomy for Graves' disease in children: Indications and complications

BackgroundThe utilization of thyroidectomy for Graves' disease remains controversial; we aim to evaluate the indications for and complications of thyroidectomy for Graves' in children.MethodsA retrospective analysis was performed on all Graves' patients who underwent thyroidectomy from 2009 to 2013 at a high volume academic center. Pediatric patients were <18years old, and a comparative analysis of indications for surgery and complications was performed.Results167 patients underwent thyroidectomy: 31 pediatric patients and 136 adults. Failure of antithyroid medications was the indication for surgery in 55% of the children vs 36% of adults (p=0.05). Mean duration of medications prior to surgery was similar. No children had failed RAI therapy prior to surgery, but 12.5% of the adult population had (p=0.04). Surgical outcomes were similar.ConclusionClinicians may be more likely to refer children who fail medical treatment to surgery over RAI. Thyroidectomy at a high volume hospital should be discussed as a treatment option for children with Graves'

Assessing American Thyroid Association Guidelines for Total Thyroidectomy in Graves' Disease

BackgroundThe American Thyroid Association (ATA) issued specific preoperative preparatory guidelines for patients undergoing thyroidectomy for treatment of Graves' disease. Our goal is to determine if compliance with these guidelines is associated with better outcomes.MethodsA retrospective review of a prospectively maintained database identified 228 patients with Graves' disease who underwent total thyroidectomy between August 2007 and May 2015. Patients treated in compliance with ATA guidelines were compared with those not in full compliance with the current preparatory guidelines.ResultsAt the time of surgery, 52% of all patients followed ATA guidelines. Patients who were prepped per ATA guidelines had fewer episodes of intraoperative tachycardia (0.3 versus 4.5, P = 0.04) but had no difference in peak systolic blood pressure or in number of episodes of systolic blood pressure > 180 mmHg. ATA prepped and nonprepped patients had similar mean operating room time and length of stay. ATA prepped and nonprepped patients had similar complication rates, including transient hypocalcemia (30.4% versus 25.5%, P = 0.45), prolonged hypoparathyroidism (0.98% versus 4.3%, P = 0.15), hoarse voice (10.8% versus 7.5%, P = 0.42), permanent recurrent laryngeal nerve paralysis (2.9% versus 2.1%, P = 0.71), and hematoma (2.9% versus 0%, P = 0.09).ConclusionsOur data suggest that compliance with ATA guidelines for thyroidectomy preparation is not essential for a successful surgical outcome. Although preparation per the guidelines decreased the frequency of intraoperative tachycardia, it did not impact intraoperative hypertension, operating room time, or postoperative complications