Assessing Adequacy: A Meta-Analysis of Rapid Onsite Evaluation of Thyroid Nodules.

INTRODUCTION: Fine-needle aspiration (FNA) is the standard form of preoperative evaluation of thyroid nodule cytological status. A significant number FNAs are classified as inadequate for interpretation, requiring a repeat FNA which is potentially avoidable, costly, and delays treatment. To address these concerns and maximize first-time FNA adequacy, rapid onsite evaluation (ROSE) of FNA specimens was introduced. Our study aims to determine the impact of ROSE on FNA adequacy. METHODS: PubMed, Embase, and Web of Science were searched for primary articles assessing the adequacy of ROSE in thyroid nodules. RESULTS: A total of 17 studies were included for a total of 24,649 thyroid nodes. Thirteen thousand two hundred fifteen (53.6%) thyroid nodules were assessed utilizing ROSE and 11,434 (46.4%) were not. Pooled adequacy increased significantly from 76% without ROSE to 92% with rose (P = 0.001). Use of ROSE increased the odds of adequate FNA by 22% (risk ratio (RR) = 1.22, 95% confidence interval (CI) = 1.12-1.32). At institutions with less than 85% effective diagnostic adequacy without ROSE, the risk for diagnostic adequacy increased by 28% with ROSE implementation (RR = 1.28, 95% CI = 1.20-1.37). In contrast, in studies reported from institutions with an effective diagnostic rate greater than 85% without the use of ROSE, the diagnostic adequacy only increased by 5% with ROSE implementation (RR = 1.05, 95% CI = 1.03-1.06). CONCLUSIONS: The use of ROSE during first-time FNA of thyroid nodules can significantly improve adequacy, especially at institutions with baseline high inadequacy rates. Implementation of ROSE can reduce repeat FNAs and its associated consequences.

Cardiovascular Health by Graves' Disease Management Modality - Surgery Versus Radioactive Iodine Versus Antithyroid Medications: A Network Meta-Analysis.

INTRODUCTION: Graves' disease is an autoimmune disorder of the thyroid gland associated with the overproduction of thyroid hormones. Excess secretion of thyroid hormones leads to cardiovascular consequences. Treatment options include antithyroid medications (ATM), radioactive iodine (RAI) ablation, and total thyroidectomy. We examined the cardiovascular outcomes following Graves' disease management modality. METHODS: A systematic search was performed up to September 22nd, 2021, using PubMed, EMBASE, and Web of Science databases. We conducted a network meta-analysis analyzing cardiovascular outcomes of interest, including congestive heart failure (CHF), arrhythmia, atrial fibrillation (AF), and hypertension. RESULTS: Three studies were included in this analysis totaling 6700 patients with Graves' disease, of which 74% were female. The mean age was 44.34 y. When compared to pretreatment, management options lowered the risk of maintaining arrhythmia 81% with surgery (relative risk [RR] = 0.19; 95% confidence interval [CI] = 0.12 to 0.31), 67% with ATM (RR = 0.33; 95% CI = 0.23 to 0.49), and 50% with RAI (RR = 0.50; 95% CI = 0.13 to 1.95). Risk of maintaining CHF was reduced 80% with surgery (RR = 0.20; 95% CI = 0.08 to 0.49), 41% with ATM (RR = 0.59; 95%CI = 0.52 to 0.67), and only 7% with RAI (RR = 0.93; 95%CI = 0.68 to 1.26). Treatment-ranking analysis found all parameters, including CHF, arrhythmia, AF, and hypertension, to be in favor of surgical treatment over medical treatment and RAI ablation. CONCLUSIONS: This is the first network meta-analysis analyzing the cardiovascular outcomes in Graves' disease patients by treatment option. Our study demonstrated that surgery is superior to RAI and medical treatment.

Recommend with caution: A meta-analysis investigating papillary thyroid carcinoma tumor progression under active surveillance.

BACKGROUND: Papillary thyroid carcinoma (PTC) is an indolent disease with favorable outcomes. The non-surgical treatment approach known as active surveillance (AS) has been introduced as an alternative treatment instead of the traditional thyroidectomy. However, 10-15 % of PTC tend to progress. We sought to determine factors predicting the progression of PTC under AS. METHODS: A systematic search was performed in January 2022 using PubMed, Embase, Google Scholar, Web of Science, and ScienceDirect. PRISMA guidelines were used by multiple reviewers to extract study characteristics (author name, publication date, journal name, country, institution, and study design), as well as main outcomes and measures. A combination of utilization of thyroid replacement therapy, baseline tumor size and volume, follow-up tumor size and volume, and the presence of lymph node metastasis and its distribution, as well as surveillance duration, were the main measures of this study. RESULTS: Nine studies with 4166 patients were included, of which 354 showed tumor progression during AS (15 %; 95%CI = 7 % - 23 %). The average follow-up period was 41.58 months. The mean tumor maximum diameter was 8.54 mm (95%CI = 7.04-10.03). Tumor progression was most commonly secondary to an increase in volume by ≥50 % (75 %; 95%CI = 68 % - 80 %), then increase in diameter by ≥3 mm (41 %; 95%CI = 13 % - 76 %), and finally the development of lymph node metastasis (13 %; 95%CI = 9 % - 19 %). Approximately only 2 % of all patients thus developed new lymph node metastasis. Patient age, sex, and tumor size were not associated with higher risks of tumor progression. 12 % of AS patients eventually underwent surgery, though only 40 % (95%CI = 27 % - 53 %) of these patients displayed tumor progression. CONCLUSIONS: Our meta-analysis determined a tumor progression rate of 15 % in patients who underwent AS management, 13 % of which (2 % of all patients) developed lymph node metastasis. We found no protective or risk factors for tumor progression, and that almost half of all patients who underwent delayed surgery did so for reasons other than tumor progression. While not biopsying small (<1 cm) or very low suspicious nodules is already recommended, AS may be an appropriate treatment option in patients appropriately counseled, considering the low risk of advanced tumor progression but also the considerable patient population who fail to adhere to treatment. Alternatively, in aim of preventing overtreatment in patients who would rather take proactive measures against their low-risk carcinoma, minimally-invasive ablation techniques may be an attractive option.

Efficacy and Safety of Radiofrequency Ablation of Thyroid Nodules: A Multi-institutional Prospective Cohort Study.

BACKGROUND: Radiofrequency ablation (RFA) has been recently adopted into the practice of thyroidology in the United States, although its use as an alternative to traditional thyroid surgery in Asia and Europe came near the turn of the 21st century. In the United States, only a few studies with small sample sizes have been published to date. We examined outcomes of benign thyroid nodules treated with RFA from 2 North American institutions. METHODS: We performed a prospective, multi-institutional cohort study of thyroid nodules treated with RFA between July 2019 and January 2022. Demographics, sonographic characteristics of thyroid nodules, thyroid function profiles, procedural details, complications, and nodule volume measurements at 1, 3, 6, and 12 months follow-up were evaluated. Adjusted multivariate logistic regression analysis was performed to identify sonographic features associated with treatment failure. RESULTS: A total of 233 nodules were included. The median and interquartile range of volume reduction rate (VRR) at 1, 3, 6, and 12 months were 54% [interquartile range (IQR): 36%-73%], 58% (IQR: 37%-80%), 73% (IQR: 51%-90%), and 76% (IQR: 52%-90%), respectively ( P <0.001). Four patients presented with toxic adenomas. All patients were confirmed euthyroid at 3-month postprocedure follow-up. Two patients developed temporary hoarseness of voice, but no hematoma or nodular rupture occurred postprocedure. Elastography was significantly associated with VRR. Compared with soft nodules, stiff nodules were more likely to have a lower VRR (odds ratio: 11.64, 95% confidence interval: 3.81-35.53, P <0.05), and mixed elasticity was also more likely to have a lower VRR (odds ratio: 4.9; 95% confidence interval: 1.62-14.85, P <0.05). CONCLUSIONS: This is the largest multi-institutional North American study examining thyroid nodule treatment response to RFA. RFA is a safe and effective treatment option that allows preservation of thyroid function with minimal risk of procedural complications.

The Diagnostic Performance of Ultrasonography in the Evaluation of Extrathyroidal Extension in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) is an indication of disease progression and can influence treatment aggressiveness. This meta-analysis assesses the diagnostic accuracy of ultrasonography (US) in detecting ETE. A systematic review and meta-analysis were performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The areas under the curve (AUC) for summary receiver operating curves were compared. A total of 11 studies analyzed ETE in 3795 patients with PTC. The sensitivity of ETE detection was 76% (95%CI = 74-78%). The specificity of ETE detection was 51% (95%CI = 49-54%). The DOR of detecting ETE by US was 5.32 (95%CI = 2.54-11.14). The AUC of ETE detection was determined to be 0.6874 ± 0.0841. We report an up-to-date analysis elucidating the diagnostic accuracy of ETE detection by US. Our work suggests the diagnostic accuracy of US in detecting ETE is adequate. Considering the importance of ETE detection on preoperative assessment, ancillary studies such as adjunct imaging studies and genetic testing should be considered.

Radiofrequency Ablation of Indeterminate Thyroid Nodules: The First North American Comparative Analysis.

Thyroid nodules can be classified as benign, malignant, or indeterminate, the latter of which make up 10-30% of nodules. Radiofrequency ablation (RFA) has become an attractive and promising therapy for the treatment of benign thyroid nodules. However, few studies have investigated the safety and efficacy of RFA for the management of indeterminate thyroid nodules. In this study, 178 patients with thyroid nodules diagnosed as benign (Bethesda II) or indeterminate (Bethesda III/IV) by preoperative cytopathological analysis were included. Patients in the benign and indeterminate cohorts had similar thyroid nodule volume reduction rates at 65.60% and 64.20%, respectively (p = 0.68). The two groups had similar nodular regrowth rates, at 11.2% for benign nodules and 9.40% for indeterminate nodules (p = 0.72). A total of three cases of transient dysphonia were reported. RFA of indeterminate thyroid nodules was comparable to that of benign thyroid nodules in all parameters of interest, including volume reduction rate. To our best knowledge, our work is the first North American analysis comparing benign and indeterminate thyroid nodules and suggests RFA to be a promising modality for the management of indeterminate thyroid nodules.

Association of BRAFV600E Mutation with the Aggressive Behavior of Papillary Thyroid Microcarcinoma: A Meta-Analysis of 33 Studies.

An association between the BRAFV600E mutation and the clinicopathological progression of papillary thyroid microcarcinoma (PTMC) has been suggested. We aimed to summarize the relevant literature and determine the predictive value of BRAFV600E mutation in predicting clinical outcomes and risk stratification in patients with PTMC. A systematic search using PubMed, Cochrane, and Embase up to February 2020 was performed. A total of 33 studies met the inclusion criteria, resulting in a pool of 8838 patients, of whom 5043 (57.1%) patients were positive for BRAFV600E mutation. Tumors with positive BRAFV600E mutation had a higher tendency for multifocality (RR = 1.09, 95%CI = 1.03-1.16), extrathyroidal extension (RR = 1.79, 95%CI = 1.37-2.32), and lymph node metastasis (RR = 1.43, 95%CI = 1.19-1.71). Patients with BRAFV600E mutation were at increased risk of disease recurrence (RR = 1.90, 95%CI = 1.43-2.53). PTMC in patients positive for the BRAFV600E mutation is more aggressive than wild-type BRAF PTMC. Since BRAF-mutated PTMC is generally more resistant to radioiodine treatment, patients with BRAFV600E-mutated PTMC may require earlier management, such as a minimally invasive ablative intervention. Conservative management by active surveillance may be suitable for patients with wild-type BRAFV600E PTMC.

Radiofrequency ablation as a treatment modality for primary hyperparathyroidism: a systematic literature review.

Background: Primary hyperparathyroidism (pHPT) is an endocrine disorder typically characterized by elevated serum calcium and elevated parathyroid hormone (PTH). While parathyroidectomy is the standard treatment, non-operative intervention such as radiofrequency ablation (RFA) has been adopted as an alternative for the management of pHPT, as it has been utilized in other endocrine glands such as thyroid and adrenal. In this literature review, we aim to evaluate the current practice of RFA for pHPT. Methods: A systematic literature search using PubMed, Web of Science, and Embase through June 2022 was conducted. Studies included in the review consisted of patient cohorts who had an unequivocal diagnosis of pHPT and underwent the treatment of pHPT with RFA. When more than one study was published from a similar cohort of patients, only the study with the most number of patients was considered. Studies included were assessed for bias using the critical appraisal instruments from the Joanna Briggs Institute (JBI) System. Results: A total of 14 studies describing 167 parathyroid glands treated in 163 patients were reviewed. The overall cure rate was 91.2%, with 5 patients undergoing more than one ablation. The most common adverse effect encountered was temporary dysphonia. Incomplete ablation and missed multiglandular disease were the most common reasons for RFA treatment failure. Conclusions: RFA may be an effective and safe alternative to parathyroidectomy in select patients with a well-localized, well-located parathyroid adenoma. Additional long-term data are needed to refine its role in the pHPT treatment algorithm.

Radiofrequency ablation of thyroid nodules: a clinical review of treatment complications.

Radiofrequency ablation (RFA) is a minimally invasive ablative modality for the treatment of thyroid nodules. Reports of RFA use have demonstrated an impressive safety profile and excellent volume reduction rates between 60-90%. Given its increased popularity in the United States as well as globally, numerous recent works have been published and a discussant of relevant complications incorporating recent insight may assist practitioners in minimizing complications and optimizing patient outcomes. Herein, we provide a comprehensive and updated review of the reported complications and side effects following RFA, summarizing their frequency and clinical presentation. We also describe a means of minimizing such complications and/or side effects. Overall, the safety profile of RFA is impressive and superior to that of thyroid surgery. The overall risk of complication is reportedly 2-3%. The risk of permanent complication or severe injury is very unlikely, below 1%. Complications are infrequent, but may be nerve-related, endocrine-related, or iatrogenic-related, and consequences of localized heat delivery. The vast majority of complications related to RFA can be managed conservatively, without need for invasive measures. This review will assist surgeons and clinicians in recognizing and treating the various complications and side effects in clinical practice.

A clinical practice review of percutaneous ethanol injection for thyroid nodules: state of the art for benign, cystic lesions.

Percutaneous ethanol injection (PEI) is a widely used treatment option for cystic and predominantly cystic thyroid nodules. It has several advantages over other treatment modalities. Compared to surgery, PEI is less painful, can be performed in the outpatient setting, and carries less risk of transient or permanent side effects. Compared to other minimally invasive techniques such as radiofrequency ablation (RFA), PEI is less expensive and does not require specialized equipment. PEI performs well in the context of cystic nodules. PEI does not perform as well as other techniques in solid nodules, so its use as a primary treatment is limited to cystic and predominantly cystic thyroid nodules. However, PEI is also being explored as an adjunct treatment to improve ablation of solid nodules with other techniques. Here, we provide a clinical review discussing the genesis, mechanism of action, and patient selection with respect to ethanol ablation, as well as the procedure itself. Predictors of operative success, failure, and common adverse events are also summarized. Altogether, PEI allows impressive volume reduction rates with minimal complications. Several recent studies have also evaluated the long-term impact of PEI up to 10 years after treatment and revealed maintenance of robust treatment efficacy with no undesirable long-term sequelae. Thus, PEI remains the treatment of choice for benign but symptomatic cystic and predominantly cystic thyroid nodules.

Clinical outcomes and tumor microenvironment response to radiofrequency ablation therapy: a systematic review and meta-analysis.

Background: Radiofrequency ablation (RFA) utilizes minimally invasive high-energy current to precisely ablate tumor cells. It has been utilized in many cancer types including thyroid, lung, and liver cancer. It has been shown to provide adequate ablative margins with minimal complications; however, incomplete RFA may lead to recurrence of tumor. The underlying cellular mechanism and behavior of ablated cancer tissue is poorly understood. Methods: A systematic review was performed, searching EMBASE, Web of Science, PubMed, and Scopus for studies published up to March 2022 and reported following PRISMA guidelines. Collection was performed by two groups of investigators to avoid risk of bias. The Cochrane Collaboration's tool was used for assessing risk of bias. We identified human, in vivo, and in vitro research studies utilizing RFA for tumor tissues. We required that the studies included at least one of the following: complications, recurrence, or survival, and took interest to studies identifying cellular signaling pathway patterns after RFA. Descriptive statistical analysis was performed in 'R' software including mean and confidence interval. Results: The most frequent cancers studied were liver and lung cancers accounting for 57.4% (N=995) and 15.4% (N=267), followed by esophageal (N=190) and breast cancer (N=134). The most common reported complications were bleeding (19%) and post-operative pain (14%). In our literature search, four independent studies showed upregulation and activation of the VEGF pathway following RFA, four showed upregulation and activation of the AKT pathway following RFA, three studies demonstrated involvement of matrix metalloproteinases, and four showed upregulation of c-Met protein following RFA. Conclusions: In our review and meta-analysis, we identify several proteins and pathways of interest of which are important in wound healing, angiogenesis, and cellular growth and survival. These proteins and pathways of interest may implicate areas of research towards RFA resistance and cancer recurrence.

Diagnostic utility of RAS mutation testing for refining cytologically indeterminate thyroid nodules.

RAS mutations are prevalent in indeterminate thyroid nodules, but their association with malignancy risk and utility for diagnosis remains unclear. We performed a systematic review and meta-analysis to establish the clinical value of RAS mutation testing for cytologically indeterminate thyroid nodules. PubMed and Embase were systematically searched for relevant studies. Thirty studies comprising 13,328 nodules met the inclusion criteria. Random effects meta-analysis synthesized pooled estimates of RAS mutation rates, risk of malignancy with RAS positivity, and histologic subtype outcomes. The pooled mutation rate was 31 % (95 % CI 19-44 %) among 5,307 indeterminate nodules. NRAS mutations predominated at 67 % compared to HRAS (24 %) and KRAS (12 %). The malignancy rate with RAS mutations was 58 % (95 %CI=48-68 %). RAS positivity increased malignancy risk 1.7-fold (RR 1.68, 95 %CI=1.21-2.34, p=0.002), with significant between-study heterogeneity (I2=89 %). Excluding one outlier study increased the relative risk to 1.75 (95 %CI=1.54-1.98) and I2 to 14 %. Funnel plot asymmetry and Egger's test (p=0.03) indicated potential publication bias. Among RAS-positive malignant nodules, 38.6 % were follicular variant papillary carcinoma, 34.1 % classical variant, and 23.2 % follicular carcinoma. No statistically significant difference in the odds of harboring RAS mutation was found between subtypes. In conclusion, RAS mutation testing demonstrates clinical utility for refining the diagnosis of cytologically indeterminate thyroid nodules. Positivity confers a 1.7-fold increased malignancy risk, supporting use for personalized decision-making regarding surgery vs. monitoring. Follicular variant papillary carcinoma constitutes the most common RAS-positive malignant histological subtype. See also the graphical abstract(Fig. 1).

Risk Factors for Postoperative Infections Following Appendectomy of Complicated Appendicitis: A Meta-analysis and Retrospective Single-institutional Study.

Patients with complicated appendicitis have an increased risk for postoperative infections. Potential risk factors for postoperative infections through a meta-analysis and retrospective chart review are discussed. A meta-analysis consisting of 35 studies analyzing complicated appendicitis treated with an appendectomy noting at least 1 postoperative infection was performed. A retrospective review was then conducted in patients diagnosed with complicated appendicitis after appendectomy. Of 5326 patients in total, 15.4% developed postoperative infections. Laparoscopic surgery and perioperative hyperoxygenation were found to be protective factors for the development of infection. Retrospectively, 53.2% of patients presented with complicated appendicitis. Patients with complicated appendicitis were more likely to be older in age and have an increased length of stay. Patient demographics, operative time, and comorbid status had no effect on postoperative infection or readmission rate. Physicians should strongly consider minimally invasive techniques to treat all cases of complicated appendicitis irrespective of comorbidities, age, sex, or body mass index.

Completion thyroidectomy: A safe option for high-volume surgeons.

BACKGROUND: The risk of complication in patients undergoing completion thyroidectomy (cT) is mixed. Several studies report increased risk in comparison to total thyroidectomy (TT) and still others reporting a comparatively decreased risk. We compared the rates of complication in patients at our institution undergoing thyroid lobectomy (TL), (TT), and cT by a single high-volume surgeon. METHODS: We performed a single-institution retrospective cohort study. Patients undergoing TL, TT, or cT by a high-volume surgeon were included. Rates of complication were collected and compared between the three cohorts. RESULTS: A total of 310 patients were included. The overall rate of complication was 4.2%. The complication rates in the TL, TT, and cT cohorts were 1%, 7.1%, and 4.5%, respectively (p = 0.10). Transient hypocalcemia was slightly more common in the TT cohort (6.1%) as opposed to the TL (0%) or cT (0.9%) cohort (p = 0.01). The cohorts also had similar rates of recurrent laryngeal nerve signal loss leading to transient dysphonia (TL: 0% vs. TT: 1% vs. cT: 3.6%, p = 0.10). CONCLUSIONS: While rates of complication tended to predictably decrease as approaches became less extensive, there were no significant differences in complication rates among the three surgical approaches when performed by a high-volume surgeon. Considering the low rates of complication overall, patient counseling and preference should be emphasized to provide appropriate and tailored treatment plans.

From ablation to operation: Unraveling the surgical outcomes and complications of thyroidectomy after radiofrequency ablation.

BACKGROUND: Radiofrequency ablation is a minimally invasive treatment for thyroid nodules; however, concerns exist regarding its impact on subsequent thyroid surgery. We compared surgical outcomes and complications between patients undergoing thyroidectomy after radiofrequency ablation (post-radiofrequency ablation thyroidectomy group) and those without prior radiofrequency ablation (non-radiofrequency ablation thyroidectomy group). METHODS: We retrospectively analyzed thyroidectomy patients, comparing post-radiofrequency ablation thyroidectomy and non-radiofrequency ablation thyroidectomy groups, examining demographics, nodule characteristics, surgical techniques, and complications. RESULTS: The study included 96 patients (73 in the non-radiofrequency ablation thyroidectomy group and 23 in the post-radiofrequency ablation thyroidectomy group). The mean age was 53.3 ± 14.4 years, with 78.1% female patients and 36.5% African American patients. Median operative time was similar between the post-radiofrequency ablation thyroidectomy (110 minutes) and the non-radiofrequency ablation thyroidectomy (92 minutes) cohorts (P = .40). Complications were reported in 13 patients, without significant differences between groups (P = .54). No permanent complications, including nerve injury or hypoparathyroidism, were reported in either cohort. Prior radiofrequency ablation treatment did not increase the risk of complications (odds ratio = 3.48, 95% confidence interval = 0.70-17.43, P = .16). CONCLUSION: Our work found no differences in outcomes or safety in patients undergoing thyroidectomy with or without previous radiofrequency ablation treatment, potentiating the post-radiofrequency ablation thyroidectomy group as a safe management option. Accordingly, this may reassure both clinicians and patients of the safety of radiofrequency ablation in treating patients with thyroid nodules.

Can Thyroid Nodules be Managed with Radiofrequency Ablation?

Radiofrequency ablation (RFA) is an established and growing minimally-invasive technique with an impressive safety profile used to manage thyroid nodules. Beyond shorter operative and recovery times, the main advantages of RFA include the lack of an incisional scar as well as maximizing the potential for maintenance of normal thyroid function. RFA can significantly reduce nodular volume, achieving rates of 60% to 95% in a breadth of thyroid disease, including benign nodules, primary carcinomas, and recurrent malignancies. Thorough patient counselling is imperative for RFA candidates, including a discussant of complications, nodule regrowth, and the potential for a subsequent ablation session.

Bilateral nodule radiofrequency ablation in a single setting: First reported case series.

BACKGROUND: Radiofrequency ablation (RFA) is a minimally-invasive ablative technique with an impressive safety profile used to manage thyroid nodules. Current reports with RFA describe the treatment of a single nodule in a single-setting. We describe the first series of bilateral nodule RFA in a single-setting. METHODS: RFA was performed on patients with bilateral thyroid nodules in a single-setting. A cohort of randomly selected patients undergoing RFA for bilateral thyroid nodules in a separate setting was reported as a control cohort. RESULTS: A total of 12 patients were included in our series, included 6 patients in the single-setting ablation cohort. For patients with bilateral nodules treated by RFA in a separate setting, the mean volume reduction rate (VRR) at 6 months of 63.79% ± 18.86%. There were no reports of complications in the separate setting cohort. For patients with bilateral nodules treated by RFA in a single-setting, the mean VRR at 6 months was 64.% ± 18.97%. There were no reports of complications in the single-setting cohort. CONCLUSIONS: Our work describes a novel use of RFA, providing preliminary insight into its use for appropriately selected patients with bilateral thyroid nodules. Future studies with larger sample sizes are warranted to corroborate and expand on our findings.

Radiofrequency ablation of an intrathyroidal parathyroid adenoma with intraoperative parathyroid hormone monitoring: a case report of a novel technique.

Background: Primary hyperparathyroidism (PHPT) is classically treated by conventional parathyroidectomy, an open neck surgery. Radiofrequency ablation (RFA) has been shown as a safe minimally-invasive alternative to parathyroidectomy for the management of PHPT and has been shown to be effective in 60-90% of cases. Here, we present a patient successfully treated for persistent PHPT by RFA with simultaneous intraoperative parathyroid hormone (IOPTH) monitoring. Case Description: A 51-year-old female with a past medical history of resistant hypertension, hyperlipidemia, and vitamin D deficiency presented to our endocrine surgery clinic with PHPT. Neck ultrasound (US) localized a 0.79 cm lesion suggestive of a parathyroid adenoma. Parathyroid exploration resulted in the excision of two masses. IOPTH levels dropped from 259.9 to 204.7 pg/mL. No ectopic parathyroid tissue was found. Three-month follow-up demonstrated elevated calcium levels, suggesting persistent disease. A repeat neck US one-year post operation localized a suspicious hypoechoic sub-centimeter thyroid nodule, which was subsequently determined to be an intrathyroidal parathyroid adenoma. The patient elected to proceed with RFA with IOPTH monitoring, citing concern for increased risk of redo open neck surgery. Operation pursued without complication and IOPTH levels dropped from 270 to 39.1 pg/mL. The patient's only three-day post-operative complaints, occasional numbness and tingling, were completely resolved by her three-month follow up. The patient had normal PTH and calcium levels at seven months post-operation visit and was without complaint. Conclusions: To our best knowledge, this is the first reported case of RFA with IOPTH monitoring used to manage a parathyroid adenoma. Our work adds to the growing literature suggesting minimally-invasive techniques, such as RFA with IOPTH, as a potential management option for treating parathyroid adenomas.

Sexual disparity and the risk of second primary thyroid cancer: a paradox.

Background: Despite extensive research on sex differences in primary thyroid cancer, there is a lack of data on the role of sex in the risk of developing second primary thyroid cancer (SPTC). We aimed to investigate the risk of SPTC development according to patient sex, with an emphasis concerning previous malignancy location as well as age. Methods: Cancer survivors diagnosed with SPTC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The SEER*Stat software package obtained standardized incidence ratios (SIR) and absolute excess risks of subsequent thyroid cancer development. Results: Data for 9,730 (62.3%) females and 5,890 (37.7%) males were extracted for a total of 15,620 SPTC individuals. Asian/Pacific Islanders had the highest incidence of SPTC [SIR =2.67, 95% confidence interval (CI): 2.49-2.86]. The risk of SPTC was higher in males (SIR =2.01, 95% CI: 1.94-2.08) than when compared to females (SIR =1.83, 95% CI: 1.79-1.88; P<0.001). Head and neck tumors had significantly higher SIRs for SPTC development in males when compared to females. Conclusions: Survivors of primary malignancies have an increased risk SPTC, especially males. Our work suggests that oncologists and endocrinologists may consider the need for increased surveillance of both male and female patients given their increased risk of SPTC.

Hereditary Angioedema: Diagnosis, Clinical Implications, and Pathophysiology.

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene. HAE affects 1/50,000 people worldwide. Three main types of HAE exist: type I, type II, and type III. Type I is characterized by a deficiency in C1-INH. C1-INH is important in the coagulation complement, contact systems, and fibrinolysis. Most HAE cases are type I. Type I and II HAE result from a mutation in the SERPING1 gene, which encodes C1-INH. Formally known as type III HAE is typically an estrogen-dependent or hereditary angioedema with normal C1-INH activity. Current guidelines now recommend subdividing hereditary angioedema with normal C1 esterase inhibitor gene (HAE-nl-C1-INH formerly known as HAE type III) based on underlying mutations such as in kininogen-1 (HAE-KNG1), plasminogen gene (PLG-HAE), myoferlin gene mutation (MYOF-HAE), heparan sulfate-glucosamine 3-sulfotransferase 6 (HS3ST6), mutation in Hageman factor (factor XII), and in angiopoietin-1 (HAE-ANGPT-1). The clinical presentation of HAE varies between patients, but it usually presents with nonpitting angioedema and occasionally abdominal pain. Young children are typically asymptomatic. Those affected by HAE usually present with symptoms in their early 20s. Symptoms can arise as a result of stress, infection, or trauma. Laboratory testing shows abnormal levels of C1-INH and high levels of bradykinin. C4 and D-dimer levels can also be monitored if an acute HAE attack is suspected. Acute treatment of HAE can include IV infusions of C1-INH, receptor antagonists, and kallikrein inhibitors. Short- and long-term prophylaxis can also be administered to patients with HAE. First-line therapies for long-term prophylaxis also include IV infusion of C1-INH. This review aims to thoroughly understand HAE, its clinical presentation, and how to treat it.