Radiofrequency ablation of Bethesda category III thyroid nodules with benign molecular testing: Preliminary findings from a single institution.

BACKGROUND: The efficacy of radiofrequency ablation (RFA) in treating thyroid nodules with indeterminate cytology remains less studied. The objective of this study was to determine the efficacy of RFA in treating nodules with Bethesda III that have been molecularly profiled benign (BIII-MPN). METHODS: We included prospectively enrolled patients who underwent RFA for benign and BIII-MPN thyroid nodules. Primary outcome measures were volume reduction ratio (VRR), symptom score (range 0-10), and cosmetic score (range 0-3) at 1, 3, 6, and 12 months after RFA, as well as complication rates. RESULTS: A total of 258 nodules in 192 patients were included (benign: 238 in 174; BIII-MPN: 20 in 18). The median VRR differed insignificantly, whereas symptom and cosmetic score improvements were similar between two cohorts. BIII-MPN thyroid nodules were associated with lower rates of infection and temporary voice change. CONCLUSION: Our preliminary findings suggest that RFA may be a feasible management option for BIII-MPN thyroid nodules. However, appropriate will be important to address the important risk of potentially missed malignancies.

Optimizing Ex Vivo CAR-T Cell-Mediated Cytotoxicity Assay through Multimodality Imaging.

CAR-T cell-based therapies have demonstrated remarkable efficacy in treating malignant cancers, especially liquid tumors, and are increasingly being evaluated in clinical trials for solid tumors. With the FDA's initiative to advance alternative methods for drug discovery and development, full human ex vivo assays are increasingly essential for precision CAR-T development. However, prevailing ex vivo CAR-T cell-mediated cytotoxicity assays are limited by their use of radioactive materials, lack of real-time measurement, low throughput, and inability to automate, among others. To address these limitations, we optimized the assay using multimodality imaging methods, including bioluminescence, impedance tracking, phase contrast, and fluorescence, to track CAR-T cells co-cultured with CD19, CD20, and HER2 luciferase reporter cancer cells in real-time. Additionally, we varied the ratio of CAR-T cells to cancer cells to determine optimal cytotoxicity readouts. Our findings demonstrated that the CAR-T cell group effectively attacked cancer cells, and the optimized assay provided superior temporal and spatial precision measurements of ex vivo CAR-T killing of cancer cells, confirming the reliability, consistency, and high throughput of the optimized assay.

The Role of Radiofrequency Ablation in Benign and Malignant Thyroid Nodules.

Radiofrequency ablation (RFA) offers a minimally invasive solution for benign, autonomously functioning (AFTN), and malignant thyroid nodules. The technique utilizes high-frequency alternating current to induce coagulative necrosis, effectively destroying target tissue. RFA is performed in the outpatient setting with local anesthesia and sonographic guidance. RFA is effective in producing substantial volume reduction rates in benign nodules and is emerging as a favorable option in AFTN and papillary thyroid microcarcinoma. RFA's advantages include lower complication rates, minimal scarring, and improved quality-of-life outcomes compared to surgery. However, its efficacy in larger and recurrent malignancies requires further investigation.

Trends in thyroid function following radiofrequency ablation of benign, nonfunctioning thyroid nodules: A single institution review.

BACKGROUND: Radiofrequency ablation (RFA) effectively reduces volume and improves symptoms of benign, non-functioning thyroid nodules (NFTNs). Given RFA's unclear impact on thyroid function, we examined post-RFA trends in thyroid hormones and antibodies. METHODS: A retrospective cross-sectional analysis was conducted of patients treated at Columbia University with RFA for benign NFTNs between August 2019 and July 2023. Thyroid function tests were recorded pre-RFA and repeated 3, 6, and 12 months post-RFA. RESULTS: We analyzed 185 patients with 243 benign NFTNs who underwent RFA. Volume reduction ratio increased post-RFA. Mean TSH increased to 2.4 mlU/L (p â€‹= â€‹0.005) at 3 months post-RFA and decreased to 1.8 mlU/L (p â€‹= â€‹0.551) by 12 months post-RFA. Tg and TPO antibody levels peaked at 6 months post-RFA (103.1 IU/mL, p â€‹= â€‹0.868 and 66.6 IU/mL, p â€‹= â€‹0.523, respectively). CONCLUSIONS: With expected volume reduction post-RFA, we observed transient relative hypothyroidism as well as transient increases in thyroid antibodies, with normalization of these changes within 12 months.

Molecular Testing for Bethesda III Thyroid Nodules: Trends in Implementation, Cytopathology Call Rates, Surgery Rates, and Malignancy Yield at a Single Institution.

Background: Molecular testing (MT) has become standard practice to more accurately rule out malignancy in indeterminate Bethesda III (BIII) thyroid lesions. We sought to assess the adoption of this technology and its impact on cytology reporting, malignancy yield, and rates of surgery across community and academic sites affiliated with a tertiary medical center. Methods: We performed a retrospective cross-sectional study including all fine-needle aspirations (FNAs) analyzed at our institution from 2017 to 2021. We analyzed trends in MT utilization by platform and by community or academic site. We compared BIII call rates, MT utilization rates, rates of subsequent surgery, and malignancy yield on final pathology before and after MT became readily available using chi-square analysis and linear regression. Results: A total of 8960 FNAs were analyzed at our institution from 2017 to 2021. There was broad adoption of MT across both community and academic sites. There was a significant increase in both the BIII rate and the utilization of MT between the pre- and post-MT periods (p < 0.001 and p < 0.001). There was no significant change in the the malignancy yield on final pathology (57.1% vs. 50.0%, p = 0.347), while the positive predictive value of MT decreased from 85% to 50% (p = 0.008 [confidence interval 9.5-52.5% decrease]). Conclusions: The use of MT increased across the institution over the study period, with the largest increase seen after a dedicated pass for MT was routinely collected. This increased availability of MT may have led to an unintended increase in the rates of BIII lesions, MT utilization, and surgery for benign nodules. Physicians who use MT should be aware of potential consequences of its adoption to appropriately counsel patients.

Does the Adoption of Molecular Testing Cause Decreased Thyroidectomy Rates in a National Cohort? A Quasiexperimental Study of High- Versus Low-Adoption States.

Background: Over the last decade, the utilization of molecular testing (MT) for the evaluation of thyroid nodules has increased. Rates and patterns of adoption of MT and its effect on thyroidectomy rates nationally are unknown. Varying rates of MT adoption at the state level provide an opportunity to study the effects of MT on thyroidectomy rates using a quasiexperimental study design. Methods: We performed a retrospective analysis of American adult patients in the Merative™ MarketScan® Research Databases who underwent thyroid fine-needle aspiration (FNA) from 2011 to 2021. MT included commercially available DNA and RNA platforms and traditional targeted mutational analysis. Interrupted time series analysis was used to evaluate the inflection of MT adoption and thyroidectomy rates after 2015. Difference-in-differences (DID) analysis was used to causally analyze the effect of MT adoption on thyroidectomy rates in high-adoption (at least a 10% increase in MT utilization) versus low-adoption states (no more than 5% increase in MT utilization) from 2015 to 2021. Results: We identified 471,364 patients who underwent thyroid FNA. The utilization of MT increased over the study period from 0.01% [confidence interval, CI: 0.00% to 0.02%] to 10.1% [CI: 9.7% to 10.5%], in 2021, with an immediate (ß2 = 1.61, p = 0.002) and deeper (ß3 = 0.6, p < 0.001) increase in MT adoption after 2015. Utilization of MT was lower in black patients, the elderly, rural areas, and patients with Medicaid (p < 0.05). Thyroidectomy rates were inversely correlated with MT utilization (r = -0.98, p < 0.0001). From 2015 to 2021, the average MT utilization rate increased from 2.4% to 15.3% in high-adoption states and 1.6% to 5.6% in low-adoption states. In low-adoption states, thyroidectomy rates decreased more but to similar levels (18.5-13.2%) compared with high-adoption states (15.9-13.4%) with an adjusted DID rate of -3.3% [CI -5.6% to -0.8%]. Conclusions: The acceleration in adoption of MT after 2015 likely coincides with the publication of American Thyroid Association guidelines. Black, elderly, and rural patients are less likely to receive MT. Although thyroidectomy rates were inversely correlated with MT utilization, our study suggests that this correlation is not causal. The effect of MT on thyroidectomy rates may be overshadowed by decreasing aggressiveness of thyroid nodule evaluation.

A national study of postoperative thyroid hormone supplementation rates after thyroid lobectomy.

BACKGROUND: The American Thyroid Association updated guidelines in 2015 to allow lobectomy for low-risk thyroid cancers. The objectives of this study were (1) to determine thyroid hormone supplementation rates after lobectomy and (2) to evaluate the effect of the American Thyroid Association guideline change on lobectomy and hormone supplementation rates among thyroid cancer patients. METHODS: The Merative MarketScan Databases was used to identify adult (≥age 18) patients who underwent thyroidectomy for benign nodules or thyroid cancer. The association between indication for surgery and postoperative thyroid hormone supplementation was examined using χ2 analyses and multivariable logistic regression models. Among patients with thyroid cancer, lobectomy and hormone supplementation rates were compared in the periods before (2008-2015) and after the guideline change (2016-2019). RESULTS: Of the 81,926 patients identified, 33,756 (41.2%) underwent thyroid lobectomy, 45,104 (55.1%) underwent total thyroidectomy, and 3,066 (3.7%) underwent completion thyroidectomy. Patients who underwent lobectomy for malignancy were significantly more likely to require hormone supplementation (59.3% vs 39.4% [P < .001], adjusted odds ratio 2.34 [95% confidence interval 2.20-2.48]) compared to those with benign disease. Compared to the 2008 to 2015 period, the proportion of patients who underwent lobectomy for thyroid cancer was higher in the 2016 to 2019 period (34.3% vs 30.3%, P < .001), with fewer patients requiring completion thyroidectomy (25.6% vs 29.8%, P < .001) and thyroid hormone supplementation (56.9% vs 60.1%, P = .04). CONCLUSION: The postoperative thyroid hormone supplementation rate was significantly higher in patients who had thyroid cancers compared to benign diseases. After the American Thyroid Association guidelines changed, lobectomy rates increased significantly without a concomitant increase in the completion of thyroidectomy.

The impact of social determinants of health on thyroid cancer mortality and time to treatment.

BACKGROUND: Whereas racial disparities in thyroid cancer care are well established, the role of social determinants of health is less clear. We aimed to assess the individual and cumulative impact of social determinants of health on mortality and time to treatment among patients with thyroid cancer. METHODS: We collected social determinants of health data from thyroid cancer patients registered in the National Cancer Database from 2004 to 2017. We created a count variable for patients in the lowest quartile of each social determinant of health (ie, low income, low education, and no insurance). We assessed the association of social determinants of health with mortality and time to treatment and the association between cumulative social determinants of health count and time to treatment using Cox regression. RESULTS: Of the 142,024 patients we identified, patients with longer time to treatment had greater mortality compared to patients treated within 90 days (90-180 days, adjusted hazard ratio 1.21 (95% confidence interval 1.13-1.29, P < .001); >180 days, adjusted hazard ratio 1.57 (95% confidence interval 1.41-1.76, (P < .001). Compared to patients with no adverse social determinants of health, patients with 1, 2, or 3 adverse social determinants of health had a 10%, 12%, and 34%, respectively, higher likelihood of longer time to treatment (1 social determinant of health, hazard ratio 0.90, 95% confidence interval 0.89-0.92, P < .001; 2 social determinants of health, hazard ratio 0.88, 95% confidence interval 0.87-0.90, P < .001; 3 social determinants of health, hazard ratio 0.66, 95% confidence interval 0.62-0.71, P < .001 for all). On subgroup analysis by race, each adverse social determinant of health was associated with an increased likelihood of a longer time to treatment for Black and Hispanic patients (P < .05). CONCLUSION: A greater number of adverse social determinants of health leads to a higher likelihood of a longer time to treatment for patients with thyroid cancer, which, in turn, is associated with an increased risk for mortality.

Cell Type-Specific Whole-Genome Landscape of ΔFOSB Binding in the Nucleus Accumbens After Chronic Cocaine Exposure.

BACKGROUND: The ability of neurons to respond to external stimuli involves adaptations of gene expression. Induction of the transcription factor ΔFOSB in the nucleus accumbens, a key brain reward region, is important for the development of drug addiction. However, a comprehensive map of ΔFOSB's gene targets has not yet been generated. METHODS: We used CUT&RUN (cleavage under targets and release using nuclease) to map the genome-wide changes in ΔFOSB binding in the 2 main types of nucleus accumbens neurons-D1 or D2 medium spiny neurons-after chronic cocaine exposure. To annotate genomic regions of ΔFOSB binding sites, we also examined the distributions of several histone modifications. Resulting datasets were leveraged for multiple bioinformatic analyses. RESULTS: The majority of ΔFOSB peaks occur outside promoter regions, including intergenic regions, and are surrounded by epigenetic marks indicative of active enhancers. BRG1, the core subunit of the SWI/SNF chromatin remodeling complex, overlaps with ΔFOSB peaks, a finding consistent with earlier studies of ΔFOSB's interacting proteins. Chronic cocaine use induces broad changes in ΔFOSB binding in both D1 and D2 nucleus accumbens medium spiny neurons of male and female mice. In addition, in silico analyses predict that ΔFOSB cooperatively regulates gene expression with homeobox and T-box transcription factors. CONCLUSIONS: These novel findings uncover key elements of ΔFOSB's molecular mechanisms in transcriptional regulation at baseline and in response to chronic cocaine exposure. Further characterization of ΔFOSB's collaborative transcriptional and chromatin partners specifically in D1 and D2 medium spiny neurons will reveal a broader picture of the function of ΔFOSB and the molecular basis of drug addiction.

If the price is right: Cost-effectiveness of radiofrequency ablation versus thyroidectomy in the treatment of benign thyroid nodules.

BACKGROUND: Radiofrequency ablation is an emerging technology in the United States to treat benign thyroid nodules. The cost-effectiveness of radiofrequency ablation in comparison with traditional thyroidectomy is unknown. METHODS: A patient-level state transition microsimulation decision model was constructed comparing radiofrequency ablation with lobectomy in the management of benign thyroid nodules. Our base case was a 45-year-old woman with a solitary 30-cm3 nodule. Estimates of health utilities, complications, and mortality were obtained from the literature, and costs were estimated using Medicare reimbursement data. The primary outcomes of interest included total cost, quality-adjusted life years, and incremental cost-effectiveness ratios. All model estimates were subjected to 1-way sensitivity analyses to identify factors that strongly influence cost-effectiveness. A probabilistic sensitivity analysis was run across 1 million simulations to gauge outcome confidence with a willingness-to-pay threshold set at $100,000/quality-adjusted life year. RESULTS: Radiofrequency ablation was assumed to cost $5,000, with an initial success rate of 78%. Patients with volume reduction ratio <50% underwent a second treatment of radiofrequency ablation. Radiofrequency ablation represented the dominant strategy, yielding 21.31 quality-adjusted life years for a total cost of $16,563 in comparison to lobectomy, which yielded 21.13 quality-adjusted life years for a total cost of $19,262. In a 1-way sensitivity analysis varying the cost of radiofrequency ablation across of range of values, the radiofrequency ablation strategy remained cost-effective until the cost of radiofrequency ablation exceeded $12,330 at willingness-to-pay $50,000 or $17,950 at willingness-to-pay $100,000. CONCLUSION: Radiofrequency ablation is a cost-effective strategy in the treatment of benign thyroid nodules but is most sensitive to the cost of radiofrequency ablation.

Phenoxybenzamine is no longer the standard agent used for alpha blockade before adrenalectomy for pheochromocytoma: A national study of 552 patients.

BACKGROUND: Phenoxybenzamine has been the standard agent for blockade before adrenalectomy for pheochromocytoma. However, high cost and limited availability have hampered its use. This study investigated whether other agents have supplanted the use of phenoxybenzamine as the first-line agent for alpha blockade in pheochromocytoma. METHODS: We performed a retrospective analysis of patients in the IBM MarketScan Database who underwent adrenalectomy for pheochromocytoma (2008-2019). Patients were categorized as having been blocked with phenoxybenzamine, selective alpha blockers, calcium channel blockers and/or beta blockers, or none of the above. The outcomes included prescription costs, perioperative costs, and length of stay. RESULTS: A total of 552 patients were identified; 58.7% were female, and the median age was 49 (interquartile range 40-57) years. In total, 291 (52.7%) patients were blocked with phenoxybenzamine, 114 (20.7%) with selective alpha blockers, 42 (7.6%) with only calcium channel blockers and/or beta blockers, and 76 (13.8%) with none. The proportion of patients blocked with phenoxybenzamine decreased from 71.0% in 2008 to 21.2% in 2019. The proportion of patients blocked with selective alpha blockers increased from 6.5% in 2008 to 42.4% and in 2019. The median cost of phenoxybenzamine increased from $722 (interquartile range $441-$1,514) in 2008 to $9,616 (interquartile range $5,049-$16,373) in 2019 (P < .001). Length of stay (2 [interquartile range 1-4] days vs 2 [interquartile range 0-3] days) and total perioperative costs ($24,250 [interquartile range $17,462-$33,849] vs $22,098 [interquartile range $16,341-$29,178] between phenoxybenzamine and selective alpha blocker groups were similar. CONCLUSION: There has been a significant shift away from phenoxybenzamine for preoperative blockade before resection of pheochromocytoma. Selective alpha blockers and calcium channel blockers are increasingly used, likely due to reduced costs, without compromised length of stay or intensive care unit admission.

Limited disease progression in endocrine surgery patients with treatment delays due to COVID-19.

BACKGROUND: The COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans. METHODS: American Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon. RESULTS: Twelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66). CONCLUSION: Although some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.

Intraoperative Neuromonitoring: Evaluating the Role of Continuous IONM and IONM Techniques for Emerging Surgical and Percutaneous Procedures.

Intraoperative nerve monitoring (IONM) is a tool used during thyroid surgery to assist in the identification of the recurrent laryngeal nerve (RLN). Multiple IONM systems that exist for thyroidectomy require intubation with an endotracheal tube. Given that one of the advantages of thermal ablation procedures, such as radiofrequency ablation, is that they can be done safely without the use of general anesthesia, nerve monitoring systems that utilize cutaneous surface electrodes have been developed, though are not widely available in the United States. This article will review the use of IONM for RFA including the cutaneous surface electrode system.

Ethanol ablation for the treatment of benign thyroid nodules.

BACKGROUND: Ethanol ablation (EA) is a non-surgical option for the treatment of benign cystic thyroid nodules. This study summarizes our preliminary experience with the efficacy and safety of EA. METHODS: A retrospective analysis was performed of patients undergoing EA for symptomatic, benign, cystic and predominantly cystic (≥75%) thyroid nodules. Baseline nodule volume, cosmetic scores, and symptom scores were assessed, as well as volume reduction ratio (VRR), cosmetic and symptom scores at post-procedure months 1, 3, 6, and 12. RESULTS: 31 patients underwent an uncomplicated EA for a single cyst with an average volume of 21.3 cc (range: 1.7-101.4 cc). Follow-up was limited by the COVID-19 pandemic. Mean nodule VRRs were 66 ± 20% (1 m, n = 17), 87 ± 15% (3 m, n = 9), 72 ± 20% (6 m, n = 7), and 78% (12 m, n = 3). Mean symptom and cosmetic scores decreased concurrently post-procedure. CONCLUSION: EA is a safe, effective option for benign cystic and predominantly cystic thyroid nodules.

Analyzing the adoption of radiofrequency ablation of thyroid nodules using the diffusion of innovations theory: understanding where we are in the United States?

Thyroid nodules are very common and found in up to 68% of the general U.S. population on ultrasound. Although thyroidectomy has long been the mainstay of treatment for malignant and symptomatic benign thyroid nodules, various interventional ablative techniques have emerged in the last couple of decades as alternative non-surgical treatment options. Globally, the most widely adopted technique has been ultrasound-guided radiofrequency ablation (RFA). RFA of thyroid nodules was first performed in 2002, and there has been an expanding body of evidence since 2006 showing that RFA and other interventional ablative techniques are effective treatments for benign solid thyroid nodules, toxic adenomas, and thyroid cysts. More recently, evidence has emerged that these techniques may be effective treatment for low-risk thyroid cancer and recurrent disease. Despite these findings, the United States has been slow to adopt these techniques, with only a single publication on RFA more than a decade after the first series was published. EM Rogers' Diffusion of Innovation Theory provides us the appropriate lens to carefully analyze the process of adoption of RFA for thyroid nodules-to understand where we are currently, as well as, the important next steps that must be accomplished in order for RFA and other ablative techniques to be successfully adopted into the management algorithm of thyroid nodules in the United States.

Primary Hyperparathyroidism Is Associated With Shorter QTc Intervals, but Not Arrhythmia.

CONTEXT: Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited. OBJECTIVE AND DESIGN: Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD). PARTICIPANTS AND SETTING: Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018. METHODS AND OUTCOMES: Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression. RESULTS: A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P < 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P < 0.001) and hypertension (50.1% vs 42.2%, P < 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P < 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates. CONCLUSIONS: In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG.