Do Ultrasound Patterns and Clinical Parameters Inform the Probability of Thyroid Cancer Predicted by Molecular Testing in Nodules with Indeterminate Cytology?

Background: Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further inform the risk of thyroid cancer in nodules predicted to be positive or negative by MT remains unknown. The aim of this study was to test if clinical parameters, including patient age, sex, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] vs. American College of Radiology Thyroid Image Reporting and Data System [TI-RADS] systems), radiation exposure, or family history of thyroid cancer can modify the probability of thyroid cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) predicted by MT. Methods: We studied 257 thyroid nodules in 232 patients from 10 study centers with indeterminate fine needle aspiration cytology and informative MT results using the ThyroSeq v3 genomic classifier (TSv3). Univariate and multivariate logistic regression was used for data analysis. Results: The presence of cancer/NIFTP was associated with positive TSv3 results (odds ratio 61.39, p < 0.0001). On univariate regression, patient sex, age, and Bethesda category were associated with cancer/NIFTP probability (p < 0.05 for each). Although ATA (p = 0.1211) and TI-RADS (p = 0.1359) US categories demonstrated positive trends, neither was significantly associated with cancer/NIFTP probability. A multivariate regression model incorporating the four most informative non-MT covariates (sex, age, Bethesda category, and ATA US pattern; Model No. 1) yielded a C index of 0.653; R2 = 0.108. When TSv3 was added to Model number 1, the C index increased to 0.888; R2 = 0.572. However, age (p = 0.341), Bethesda category (p = 0.272), and ATA US pattern (p = 0.264) were nonsignificant, and other than TSv3 (p < 0.0001), male sex was the only non-MT parameter that potentially contributed to cancer/NIFTP risk (p = 0.095). The simplest and most efficient clinical model (No. 3) incorporated TSv3 and sex (C index = 0.889; R2 = 0.588). Conclusions: In this multicenter study of thyroid nodules with indeterminate cytology and MT, neither the ATA nor TI-RADS US scoring systems further informed the risk of cancer/NIFTP beyond that predicted by TSv3. Although age and Bethesda category were associated with cancer/NIFTP probability on univariate analysis, in sequential nomograms they provided limited incremental value above the high predictive ability of TSv3. Patient sex may contribute to cancer/NIFTP risk in thyroid nodules with indeterminate cytology.

Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study.

Importance: Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery. Objective: To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules. Design, Setting, and Participants: Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules. Interventions: A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3). Main Outcomes and Measures: The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules. Results: Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%. Conclusions and Relevance: In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.

Central venous parathyroid hormone monitoring using a novel, specific anatomic method accurately predicts cure during minimally invasive parathyroidectomy.

BACKGROUND: Measurement of intraoperative parathyroid hormone (PTH) levels is an important adjunct to confirm biochemical cure during parathyroidectomy. The purpose of this study was to evaluate a simplified anatomic technique for PTH sampling from the central veins through the minimally invasive neck incision, and to compare the predictive accuracy of central and peripheral PTH values. METHODS: A specific anatomic method for central PTH sampling was employed in 48 patients. Samples were drawn simultaneously from peripheral and central veins at baseline and 10 minutes postexcision of all hyperfunctioning parathyroid glands. RESULTS: The central venous PTH levels independently predicted biochemical cure according to the Miami criterion in all the patients. There was no significant difference in the postexcision central and peripheral values, which were 24.40 + 1.86 and 21.69 + 1.74, respectively (P = .877, ANOVA test). CONCLUSIONS: This study provides the original description of a simplified technique for measurement of intraoperative PTH levels in the central veins with direct comparison to peripheral venous levels, and confirmation of accuracy in predicting biochemical cure when relying on centrally obtained values alone.

Improving Minimally Invasive Adrenalectomy: Selection of Optimal Approach and Comparison of Outcomes.

INTRODUCTION: Minimally invasive adrenalectomy is commonly performed by either a transperitoneal laparoscopic (TLA) or posterior retroperitoneoscopic (PRA) approach. Our group described the technique for robot-assisted PRA (RAPRA) in 2010. Few studies are available that directly compare outcomes between the available operative approaches. We reviewed our results for minimally invasive adrenalectomy using the three different approaches over a 10-year period. METHODS: Between January 2005 and April 2015, 160 minimally invasive adrenalectomies were performed. Clinicopathologic data were prospectively collected and retrospectively analyzed. The primary endpoints evaluated were operative time, blood loss, length of stay (LOS), and morbidity. RESULTS: The study included 67 TLA, 76 PRA, and 17 RAPRA procedures. Tumor size for PRA/RAPRA was smaller than for patients undergoing TLA (2.38 vs 3.6 cm, p ≤ 0.0001). Procedure time was shorter for PRA versus TLA (133.3 vs 152.8 min, p = 0.0381), as was LOS (1.85 vs 2.82 days, p = 0.0145). Procedure time was longer in RAPRA versus TLA/PRA (177 vs 153/133 min, p = 0.008), but LOS was significantly decreased (1.53 vs 2.82/1.85 days, p = 0.004). CONCLUSIONS: Minimally invasive adrenalectomy is associated with expected excellent outcomes regardless of approach. In our series, the posterior approach is associated with decreased operative time and LOS. Robotic technology provides potential advantages for the surgeon at the expense of more complex setup requirements and costs. Further study is required to demonstrate clear benefit of one surgical approach. Utilization of the entire spectrum of available operative techniques can allow for selection of the optimal approach based on individual patient factors.