Learning Objectives
Identify and evaluate a patient with a diagnosis of medullary thyroid cancer.
Utilize genetic testing for the RET proto‐oncogene and explain how the location of the mutation ...affects the risks for the patient.
Select among the surgical treatment options for patients with medullary thyroid cancer, including prophylactic surgery in genetic carriers.
Medullary thyroid cancer (MTC) typically accounts for 3%–4% of all thyroid cancers. Although the majority of MTCs are sporadic, 20% of cases are hereditary. Hereditary MTC can be found in multiple endocrine neoplasia 2A or 2B or as part of familial MTC based on a specific germline mutation in the RET proto‐oncogene. This article discusses the current approaches available for the diagnosis, evaluation, and management of patients and their family members with suspected MTC. The disease is predominantly managed surgically and typically requires a total thyroidectomy and lymph node dissection. A review of recent guidelines on the extent and timing of surgical excision is discussed. There are not very many effective systemic treatment options for MTC, but several emerging therapeutic targets have promise.
摘要
甲状腺髓样癌 (MTC) 在所有甲状腺癌中通常占 3%–4%。虽然大多数 MTC 呈散发性，但有 20% 的病例是遗传性病例。根据 RET 原癌基因上的一个特定胚系突变，遗传性 MTC 可归类于 2A 或 2B 型多发性内分泌肿瘤综合征或者家族性 MTC 的组成部分。本文讨论了 MTC 疑似患者及其家人的最新诊断、评估和治疗方案。该疾病的主要治疗手段是手术治疗，通常需要进行甲状腺全切术和淋巴结清扫术。本文对最新指南中的手术切除范围和时机进行了总结。针对 MTC 的有效全身治疗方案，目前还不是很多，但新近发现的若干治疗靶标为 MTC 患者带来了希望。The Oncologist 2013; 18:1093–1100
This article discusses the current approaches available for the diagnosis, evaluation, and management of patients and their family members with suspected medullary thyroid cancer. A review of recent guidelines on the extent and timing of surgical excision is discussed. There are not very many effective systemic treatment options for MTC, but several emerging therapeutic targets have promise.
Background
Parathyroidectomy has a success rate of >95 % for cure of primary hyperparathyroidism. In about 6–16 % of cases, one or more hyperfunctioning parathyroid gland(s) are found in an ectopic ...location. Accurate preoperative imaging can aid in detecting these ectopically located glands and allow a focused surgical approach with an even higher success rate. The objective of this study was to assess the utility of ultrasonography (US) and technetium-99m-sestamibi (MIBI) scans in locating ectopic parathyroid glands in previously unexplored patients who presented with primary hyperparathyroidism.
Methods
We analyzed a total of 1,562 patients who underwent surgery for hyperparathyroidism at our institution from 2000 to 2010. Ectopic parathyroid adenomas were identified in 346 of the patients (22 %). Of the 346 patients, we excluded 144 who underwent reoperations, had four-gland hyperplasia or were missing imaging details. We carefully reviewed the data, including demographics, laboratory values, preoperative localizing imaging details, and operative findings. Preoperative US and MIBI results were compared to the intraoperative findings.
Results
We analyzed 202 patients with ectopic glands for accuracy of preoperative localization. Of these 202 patients, a single adenoma was the most common (89 %) followed by double adenoma (11 %). The ectopic parathyroid glands were predominantly located in the thymus (38 %) followed by 31 % in the retroesophageal region; 18 % were intrathyroidal. Preoperative MIBI scans had a sensitivity of 89 % (161/197), whereas US had a sensitivity of 59 % (35/63) for detecting ectopic glands. Overall, both imaging modalities had a positive predictive value of 90 %, with MIBI correctly predicting ectopic glands best in the thymus, mediastinum, or the retroesophageal space, and US was most accurate at detecting intrathyroidal glands.
Conclusions
Based on the data available at our institution, MIBI has a higher sensitivity than US in correctly localizing ectopic parathyroid adenomas, but the accuracy of detection varies based on location. Both imaging techniques have a high PPV for detecting an ectopic gland. Therefore, imaging with MIBI and US can be complementary, and positive localization of an ectopic gland with either modality is highly accurate and can facilitate a more focused surgical approach.
Background
In papillary thyroid cancer, the role of lymph node dissection remains controversial, and staging systems consider metastatic lymph nodes as a binary entity. The purpose of this study was ...to determine a threshold lymph node ratio (LNR) that impacted disease-specific mortality (DSM).
Methods
We utilized the surveillance, epidemiology, and end results (SEER) database to analyze adult patients who underwent thyroidectomy with lymph node dissection. A LNR (metastatic lymph nodes to total lymph nodes) was calculated after eliminating patients with less than three nodes collected. Kaplan–Meier estimates for DSM were plotted for LNRs and compared by the log rank test. The Cox proportional hazards model was used to evaluate LNR with other known clinical and pathologic determinants of prognosis.
Results
A total of 10,955 cases contained data on lymph nodes. Median follow-up time was 25 months (range 0–59 months), and the mean LNR was 0.28 ± 0.37. After comparing Kaplan–Meier survival estimates and overall DSM rates, we found that a LNR ≥0.42 best divided those with lymph node metastasis based on DSM (
p
< 0.01). Those with a LNR ≥0.42 experienced a DSM rate of 1.72 % while those with a LNR <0.42 had a DSM rate of 0.65 % (
p
< 0.01). In addition, patients with a LNR ≥0.42 experienced a 77 % higher DSM rate compared to those with metastatic lymph nodes as a whole. When considered with other known determinants of prognosis, we found that LNR was strongly associated with DSM (hazard ratio 4.33, 95 % confidence interval 1.68–11.18,
p
< 0.01).
Conclusions
LNR is a strong determinant of DSM, and a threshold LNR of 0.42 can be used to risk-stratify patients with metastatic lymph nodes.
The purpose of this study was to identify the risk factors that predict papillary thyroid microcarcinoma (PTMC)-related death in a large patient population to determine which patients need aggressive ...treatment.
The management of PTMC is controversial and ranges from observation to total thyroidectomy. The lack of consensus is predominantly due to the general excellent overall prognosis, thereby requiring a large cohort to delineate differences in outcome.
All papillary thyroid cancer patients with tumor size of 1 cm or less in the Surveillance, Epidemiology and End Results Cancer Database from 1988 to 2007 were identified. Outcomes, including overall and disease-specific survival, were compared, and different risk groups were evaluated by multivariate analysis.
A total of 18,445 cases of PTMC with surgery were identified. The 10-year and 15-year overall survivals were 94.6% and 90.7%, respectively, while disease-specific survivals were 99.5% and 99.3%. Age greater than 45 years, male sex, African American or minority race, node metastases, extrathyroidal invasion, and distant metastases were stratified to be significant risk factors for overall survival. There were 49 thyroid cancer-related deaths. Forty-five (92%) of the 49 patients had at least 2 risk factors, and 51% of these 49 patients had 3 or more risk factors (vs 5.7% in the rest of the cohort, P < 0.001).
Although PTMC is generally associated with an excellent prognosis, 0.5% patients may die of PTMC. The presence of 2 or more risk factors is strongly associated with cancer-related mortality and can help to identify patients who should be considered for more aggressive management.
Background The impact of recent medical advances on disease presentation, extent of operation, and disease-specific survival for patients with medullary thyroid cancer is unclear. Methods We used the ...Surveillance, Epidemiology, and End Results registry to compare trends over 3 time periods, 1983–1992, 1993–2002, and 2003–2012. Results There were 2,940 patients diagnosed with medullary thyroid cancer between 1983 and 2012. The incidence of medullary thyroid cancer increased during this time period from 0.14 to 0.21 per 100,000 population, and mean age at diagnosis increased from 49.8 to 53.8 ( P < .001). The proportion of tumors ≤1 cm also increased from 11.4% in 1983–1992, 19.6% in 1993–2002, to 25.1% in 2003–2012 ( P < .001), but stage at diagnosis remained constant ( P = .57). In addition, the proportion of patients undergoing a total thyroidectomy and lymph node dissection increased from 58.2% to 76.5% during the study period ( P < .001). In the most recent time interval, 5-year, disease-specific survival improved from 86% to 89% in all patients ( P < .001) but especially for patients with regional (82% to 91%, P = .003) and distant (40% to 51%, P = .02) disease. Conclusion These data demonstrate that the extent of operation is increasing for patients with medullary thyroid cancer. Disease-specific survival is also improving, primarily in patients with regional and distant disease.
Cervical lymph nodes (LNs) in the central (level VI) and lateral (levels II-V) compartments of the neck are the most common sites of locoregional metastases associated with thyroid cancer. ...Prophylactic nodal dissections are uncommon in modern thyroid surgery and are not routinely performed due to concern for increased morbidity and do not offer improved survival. Therefore, a selective approach for LN dissections is increasingly important. Preoperatively, this is most frequently assessed with cervical ultrasound (US). Contrast-enhanced computed tomography (CT) of the neck can also be used for preoperative assessment. Both US and CT imaging can be used to characterise LNs in levels II-VI and their risk of malignancy based on size, morphology, and growth. US-guided fine-needle aspiration of equivocal LN with thyroglobulin (Tg) washout can also determine if a LN harbours malignancy. For postoperative surveillance after total thyroidectomy, both US and CT continue to play an important role at 6-12 months intervals. These patients may also benefit from additional biochemical data such as Tg levels in addition to LN and thyroid bed imaging. Thyroid uptake scans may also play a role in LN surveillance postoperatively for well-differentiated thyroid carcinoma in certain clinical contexts. Less commonly, positron emitted tomography may play a role, but is typically reserved for patients with aggressive or radioactive iodine refractory disease.
This article reviews the current surgical management of patients with secondary and tertiary hyperparathyroidism. The focus is on innovative surgical strategies that have improved the care of these ...patients over the past 10 to 15 years. Modalities such as intraoperative parathyroid hormone monitoring and radioguided probe utilization are discussed.
Abstract Background Parathyroid 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. Methods We 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. Results Of 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. Conclusions Most 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.
OBJECTIVE:The purpose of this study was to determine whether the operative approach independently influenced recurrence and to identify perioperative predictors of recurrence.
...BACKGROUND:Intraoperative parathyroid hormone (IoPTH) monitoring has enabled surgeons to perform minimally invasive parathyroidectomy (MIP). Yet, the long-term durability of this approach has recently been questioned.
STUDY DESIGN:A retrospective review was performed, and cases of initial neck surgery for nonfamilial primary hyperparathyroidism were selected for analysis. Cases were classified as either open parathyroidectomy (OP) when both sides of the neck were explored or MIP when only one side was explored. Kaplan-Meier estimates were plotted for disease-free survival, and a Cox proportional hazards model was developed to evaluate factors associated with recurrence for both the entire cohort and the MIP subset. Further comparisons were made between those who recurred and those who did not recur.
RESULTS:In the past 10-year period, 1368 parathyroid operations for primary hyperparathyroidism were performed at our institution. A total of 1006 were MIP whereas 380 were OP. There were no differences in recurrence between the MIP and OP groups (2.5% vs 2.1%; P = 0.68), and the operative approach (MIP vs OP) did not independently predict recurrent disease in our multivariate analysis. The percentage decrease in IoPTH was protective against recurrence for both the entire cohort (hazard ratio = 0.96; 95% confidence interval = 0.93–0.99; P = 0.03) and the MIP subset. A higher postoperative PTH also independently predicted disease recurrence.
CONCLUSIONS:Operative approach does not independently predict recurrent hyperparathyroidism. The percentage decrease in IoPTH is one of many adjuncts the surgeon can use to determine which patients are best served by bilateral exploration whereas the postoperative PTH can guide follow-up after parathyroidectomy.
Learning Objectives
Explain how lymph node ratio can be used to predict disease recurrence for papillary thyroid cancer.
Cite the threshold total and central lymph node ratios that best predict ...recurrence.
Describe ways in which lymph node ratio can be useful in guiding postoperative follow‐up.
Background.
Lymph node metastasis occurs in 20%–50% of patients presenting for initial treatment of papillary thyroid cancer (PTC). The significance of lymph node metastases remains controversial, and the aim of this study is to determine how the lymph node ratio (LNR) may predict the likelihood of disease recurrence.
Methods.
We conducted a retrospective review of patients undergoing total thyroidectomy for PTC at our institution from 2005 to 2010. A total LNR (positive nodes to total nodes) and central lymph node ratio (cLNR) was calculated. Regression was used to determine a threshold LNR that best predicted recurrence. Multivariate logistic regression then determined the influence of LNR on recurrence while accounting for other known predictors of recurrence. Kaplan‐Meier analysis and the log‐rank test were used to compare differences in disease‐free survival.
Results.
Of the 217 patients undergoing total thyroidectomy for PTC, 69 patients had concomitant neck dissections. Sixteen (23.2%) patients developed disease recurrence. When disease‐free survival functions were compared, we found that patients with a total LNR ≥0.7 (p < .01) or a cLNR ≥0.86 (p = .04) had significantly worse disease‐free survival rates than patients with ratios below these threshold values. Considering other known predictors of recurrence, we found that LNR was significantly associated with recurrence (odds ratio: 19.5, 95% confidence interval: 4.1–22.9; p < .01).
Conclusions.
Elevated total LNR and cLNR are strongly associated with recurrence of PTC after initial operation. LNR in PTC is a tool that can be used to determine the likelihood of the patient developing recurrent disease and inform postoperative follow‐up.
摘要
背景. 20% ∼50%的甲状腺乳头状癌（PTC）患者初次就诊时即有淋巴结转移。淋巴结转移是否有意义仍有争议，本研究旨在判断如何应用淋巴结转移率（LNR）对疾病复发风险进行预测。
方法. 对2005 ∼ 2010年因PTC在本中心接受全甲状腺切除术的患者进行回顾性分析。计算总LNR（阳性淋巴结与总淋巴结之比）和中央LNR（cLNR）。应用回归分析确定能最准确预测复发的LNR阈值。然后应用多变量逻辑回归判断LNR对复发的影响，同时亦考虑其他已知的复发预测因素。应用Kaplan‐Meier分析和log‐rank检验比较无病生存的差异。
结果. 在217例因PTC行全甲状腺切除术的患者中，69例同时进行颈部淋巴结清扫。16例患者（23.2%）疾病复发。对无病生存状态的比较显示：总LNR ≥ 0.7（p < 0.01）或cLNR ≥ 0.86（p = 0.04）患者的无病生存率低于该阈值以下的患者。考虑其他已知的复发预测因素，本研究发现：LNR与复发相关，有统计学意义（优势比：19.5，95%可信区间：4.1∼ 22.9，p < 0.01）。
结论. 总LNR和cLNR升高与PTC初次手术后复发密切相关。PTC中的LNR可作为判断患者疾病复发风险及指导术后随访的有力工具。
This study aims to determine how the lymph node ratio may be used to predict the likelihood of recurrence for patients with papillary thyroid cancer.
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