The impact of molecular testing on the surgical management of patients with thyroid nodules.

BACKGROUND: The use of molecular tests as an adjunct to FNA diagnosis of thyroid nodules has been increasing. However, the true impact of these tests on surgical practice has not been demonstrated. This study examines the usefulness of molecular testing on surgical management decisions in patients referred for thyroid surgery at a tertiary care center. METHODS: Clinical information was collected from patients who presented to Johns Hopkins Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between August 2009 and March 2013. Tests included an RNA-based gene expression classifier, a DNA-based somatic mutation panel, BRAF, NRAS, and/or RET/PTC translocation. A surgical management algorithm was created by consensus of four thyroid surgeons. Postsurgical pathology analysis in each case was then used to judge the appropriateness of the surgical decision-making and the usefulness of preoperative molecular testing, in guiding surgical planning. RESULTS: Of 114 patients assessed by preoperative molecular testing, 87 (72 %) underwent surgery. Surgical management was altered in nine (10 %) patients on the basis of molecular testing. Of these, surgical management change was appropriate, relative to the postoperative pathology analysis, for three patients and inappropriate for six patients. CONCLUSIONS: In this study, molecular testing of thyroid nodule did not alter the surgical management of the majority of patients with thyroid nodules. These results indicate that molecular testing may be overused in patients for whom the results would not change surgical management. Furthermore, our data question the usefulness of the molecular tests examined in guiding preoperative surgical decision-making.

Infrarenal transcaval extraction of intracardiac leiomyomatosis.

Intravascular leiomyomatosis is a rare, histologically benign disease, and can spread through the venous system to the right cavities of the heart. We report the case of a 39-year-old woman who presented with intravenous leiomyomatosis with extension to the right ventricle, causing heart failure. She underwent surgery successfully, undergoing a total resection of this tumor through the infrarenal cava and the hysterectomy in one surgical stage. Surgical technique considerations are discussed and the literature is reviewed.

Evaluation of the Effect of Diagnostic Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules.

IMPORTANCE: Diagnostic molecular testing is used in the workup of thyroid nodules. While these tests appear to be promising in more definitively assigning a risk of malignancy, their effect on surgical decision making has yet to be demonstrated. OBJECTIVE: To investigate the effect of diagnostic molecular profiling of thyroid nodules on the surgical decision-making process. DESIGN, SETTING, AND PARTICIPANTS: A surgical management algorithm was developed and published after peer review that incorporated individual Bethesda System for Reporting Thyroid Cytopathology classifications with clinical, laboratory, and radiological results. This algorithm was created to formalize the decision-making process selected herein in managing patients with thyroid nodules. Between April 1, 2014, and March 31, 2015, a prospective study of patients who had undergone diagnostic molecular testing of a thyroid nodule before being seen for surgical consultation was performed. The recommended management undertaken by the surgeon was then prospectively compared with the corresponding one in the algorithm. Patients with thyroid nodules who did not undergo molecular testing and were seen for surgical consultation during the same period served as a control group. MAIN OUTCOMES AND MEASURES: All pertinent treatment options were presented to each patient, and any deviation from the algorithm was recorded prospectively. To evaluate the appropriateness of any change (deviation) in management, the surgical histopathology diagnosis was correlated with the surgery performed. RESULTS: The study cohort comprised 140 patients who underwent molecular testing. Their mean (SD) age was 50.3 (14.6) years, and 75.0% (105 of 140) were female. Over a 1-year period, 20.3% (140 of 688) had undergone diagnostic molecular testing before surgical consultation, and 79.7% (548 of 688) had not undergone molecular testing. The surgical management deviated from the treatment algorithm in 12.9% (18 of 140) with molecular testing and in 10.2% (56 of 548) without molecular testing (P = .37). In the group with molecular testing, the surgical management plan of only 7.9% (11 of 140) was altered as a result of the molecular test. All but 1 of those patients were found to be overtreated relative to the surgical histopathology analysis. CONCLUSIONS AND RELEVANCE: Molecular testing did not significantly affect the surgical decision-making process in this study. Among patients whose treatment was altered based on these markers, there was evidence of overtreatment.

Parathyroid surgery can be safely performed in a community hospital by experienced parathyroid surgeons: A retrospective cohort study.

BACKGROUND: There is ongoing debate about the effectiveness and safety of performing parathyroid surgery in low-volume community hospitals. STUDY DESIGN/METHODS: Cases performed at community hospital by a group of 4 parathyroid surgeons (group 1) were reviewed. Cure and complication rates were analyzed in light of outcomes of an expert endocrine surgeon from high-volume academic center (group 2) as point of reference. RESULTS: During the respective time periods, 204 patients met inclusion criteria in group1 and 218 patients in group 2. Patient characteristics, biochemical tests, and performed localizing studies (ultrasound and sestamibi scan) were comparable between the two groups. Pathological findings, including adenoma, double adenoma, hyperplasia, and cancer were comparable. Each had comparable cure rates (97% and 99%) (p < 0.18) and complication rates (1% and 1%) (p < 0.93) for group 1 and 2, respectively. CONCLUSION: Our results showed that experienced parathyroid surgeons will achieve comparable excellent outcomes of parathyroid surgery at both community and academic-based centers. As the field of endocrine surgery evolves and matures, producing young fellowship-trained endocrine surgeons, there will be growing need for expanding the niche of endocrine surgery into community-based hospital settings, which eventually will contribute to expanding and equalizing access to high-quality surgical care across urban and rural areas.

MicroRNA Expression and Association with Clinicopathologic Features in Papillary Thyroid Cancer: A Systematic Review.

BACKGROUND: Studies have suggested that microRNAs (miR) may be useful prognostic markers and are associated with aggressive clinicopathologic features in papillary thyroid cancer (PTC). This systematic review examined associations between miRs and aggressive clinicopathologic features in PTC. METHODS: A literature search was performed within the PubMed, Embase, Cochrane, Web of Science, and Scopus databases for papers published prior to November 24, 2014. The search was performed by combining the concepts "thyroid tumor" with "microRNA" and by using "and" as the Boolean operator. Upon retrieval of candidate studies, full-text publications were reviewed in their entirety and selected if they examined the prognostic significance between miR expression and established aggressive clinicopathologic features of PTC. RESULTS: Fifteen studies from 13 unique groups that included 807 patients were reviewed. Most of the studies were retrospective, and none included patients who had undergone routine central lymph node dissection. Expression levels of miRs-21, -34b, -130b, -135b, -146b, -151, -181b, -199b-5p, -221, -222, -451, -623, -1271, -2861, and let-7e showed significant association with at least one aggressive feature, such as large tumor size, extrathyroidal extension, multifocality, lymphovascular invasion, lymph node metastases, distant metastasis, advanced American Joint Cancer Committee stage, and presence of the BRAF(V600E) mutation. Herein we summarize the literature with regard to these associations. CONCLUSION: Further studies are needed to investigate whether miRs are independent predictors of aggressive clinicopathologic features before it can be recommended that miR expression levels should be incorporated into the management algorithm for patients with PTC. A well-designed prospective study is needed to assess these potential associations.

A tertiary center's experience with second review of 3885 thyroid cytopathology specimens.

BACKGROUND: Although the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) has standardized the diagnostic terminology for thyroid fine-needle aspiration (FNA), morphological interpretation remains subjective, and interobserver discrepancies are expected. This study quantifies the frequency and magnitude of these discrepancies in a single tertiary center's experience and elucidates key factors that are associated with changes in diagnosis. METHODS: Institutional consultation for 3885 thyroid cytological samples over 45 months were reviewed. BSRTC classification made by the sending institution was compared with that of our institution. An ANOVA was performed to determine factors that may be associated with interinstitutional diagnostic differences. Histopathology diagnoses were available for 1049 (27%) nodules; the malignancy rates for inside and outside BSRTC classifications were calculated. RESULTS: There were 937 1-step changes and 301 ≥2-step diagnostic discrepancies comprising 24% and 8% of all cases, respectively. Second review decreased the indeterminate rate 38% to 28% (P < .000001). Indeterminate diagnostic category before second review, low specimen cellularity, Hashimoto's thyroiditis, and low volume of consults from the sending institution were associated with discordance. Of the 1049 thyroid nodules operated for which unequivocal histopathology was available, the malignancy rates for the BSRTC categories before and after second review were compared. Categorical upgrades were associated with a malignancy rate of 84%, whereas downgrades were associated with a malignancy rate of 38% (P < .000001). CONCLUSION: This is the largest series to date of thyroid cytology second review. The BSRTC classification changed 32% of the time, potentially resulting in significant changes in clinical and surgical management. Because certain specimen characteristics (indeterminate diagnostic category before second review, low specimen cellularity, Hashimoto's thyroiditis, and low volume of consults from the sending institution) were particularly associated with a diagnosis change, morphological second review may be of potential benefit in these settings.

Does BRAF V600E mutation predict aggressive features in papillary thyroid cancer? Results from four endocrine surgery centers.

BACKGROUND: Existing evidence is controversial regarding the association between BRAF mutation status and aggressive features of papillary thyroid cancer (PTC). Specifically, no study has incorporated multiple surgical practices performing routine central lymph node dissection (CLND) and thus has patients who are truly evaluable for the presence or absence of central lymph node metastases (CLNMs). METHODS: Consecutive patients who underwent total thyroidectomy and routine CLND at 4 tertiary endocrine surgery centers were retrospectively reviewed. Descriptive and bivariable analyses examined demographic, patient, and tumor-related factors. Multivariable analyses examined the odds of CLNM associated with positive BRAF status. RESULTS: In patients with classical variant PTC, bivariate analysis found no significant associations between BRAF mutation and aggressive clinicopathologic features; multivariate analysis demonstrated that BRAF status was not an independent predictor of CLNM. When all patients with PTC were analyzed, including those with aggressive or follicular subtypes, bivariate analysis showed BRAF mutation to be associated with LNM, advanced American Joint Committee on Cancer (AJCC) stage, and histologic subtype. Multivariable analyses showed BRAF, age, size, and extrathyroidal extension to be associated with CLNM. CONCLUSION: Although BRAF mutation was found to be an independent predictor of central LNM in the overall cohort of patients with PTC, this relationship lost significance when only classical variant PTC was included in the analysis. The usefulness of BRAF in predicting the presence of LNM remains questionable. Prospective studies are needed before BRAF mutation can be considered a reliable factor to guide the treatment of patients with PTC, specifically whether to perform prophylactic CLND.

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.