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).

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.

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.

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.

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.

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.

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.

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.

Minoxidil weakens newly synthesized collagen in fibrotic synoviocytes from osteoarthritis patients.

PURPOSE: Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by Plod2-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)ß1. METHODS: Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b histology or culture. Protein and RNA were purified from fibrotic FSCs after 8 days with or without 0.5 µM MXD and/or 4 ng/mL of TGFß1. COL1 and Pyd protein concentrations from ELISA and expression of Col1a1, Acta2, and Plod2 genes by qPCR were compared by parametric tests with α = 0.05. RESULTS: Histological LH2b expression corresponded to SFb severity. MXD attenuated COL1 output in KOA FSCs but only in the absence of TGFß1 and consistently decreased Pyd under all conditions with significant downregulation of Plod2 but minimal alterations to Col1a1 and Acta2 transcripts. CONCLUSIONS: MXD is an attractive candidate for local antifibrotic pharmacotherapy for SFb by compromising the integrity of newly formed fibrous deposits by FSCs during KOA and following arthroplasty. Targeted antifibrotic supplementation could improve physical therapy and arthroscopic lysis strategies aimed at breaking down joint scarring. However, the effect of MXD on other joint-specific TGFß1-mediated processes or non-fibrotic components requires further investigation.

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.

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.

A combination of computed tomography scan and ultrasound provides optimal detection of cervical lymph node metastasis in papillary thyroid carcinomas: A systematic review and meta-analysis.

BACKGROUND: Lymph node metastasis (LNM) in patients with papillary thyroid carcinoma (PTC) is common. This meta-analysis assesses the diagnostic accuracy of computed tomography (CT), ultrasound (US), and CT + US in detecting central and lateral LNM. METHODS: A systematic review and meta-analysis was 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 area under the curve (AUC) for summary receiver operating curves (sROC) were compared. RESULTS: The study population included 7902 patients with a total of 15 014 lymph nodes. Twenty-four studies analyzed the sensitivity of the overall neck region in which dual CT + US imaging (55.9%) had greater sensitivities (p < 0.001) than either US (48.4%) or CT (50.4%) alone. The specificity of US alone (89.0%) was greater (p < 0.001) than CT alone (88.5%) or dual imaging (86.8%). The DOR for dual CT + US imaging was greatest (p < 0.001) at 11.134, while the AUCs of the three imaging modalities were similar (p > 0.05). Twenty-one studies analyzed the sensitivity of the central neck region in which both CT (45.8%) and CT + US imaging (43.4%) had greater sensitivities (p < 0.001) than US alone (35.3%). The specificity of all three modalities was higher than 85%. The DOR for CT (7.985) was greater than US alone (4.723, p < 0.001) or dual CT + US imaging (4.907, p = 0.015). The AUC of both CT + US (0.785) and CT alone (0.785) were significantly greater (p < 0.001) than US alone (0.685). Of the 19 studies that reported lateral LNM, CT + US imaging sensitivity (84.5%) was higher than CT alone (69.2%, p < 0.001) and US alone (79.7%, p = 0.038). The specificity of all imaging techniques was all greater than 80.0%. CT + US imaging DOR (35.573) was greater than CT (20.959, p = 0.024) and US (15.181, p < 0.001) individually. The AUC of independent imaging was high (CT: 0.863, US: 0.858) and improved significantly when combined (CT + US: 0.919, p = 0.024 and p < 0.001, respectively). CONCLUSIONS: We report an up-to-date analysis elucidating the diagnostic accuracy of LNM detection by either CT, US, or in combination. Our work suggests dual CT + US to be the best for overall detection of LNM and CT to be preferable in detecting central LNM. The use of either CT or US alone may detect lateral LNM with acceptable accuracy, yet dual imaging (CT + US) significantly improved detection rates.

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.

Comparison of Medical Management versus Parathyroidectomy in Patients with Mild Primary Hyperparathyroidism: A Meta-Analysis.

BACKGROUND: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2-1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. STUDY DESIGN: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, and Web of Science by two teams of investigators. Analysis was run using R packages. RESULTS: A total of 12 publications including seven randomized control, two prospective, and three retrospective trials with a total of 1346 patients were included for analysis. The average follow-up for all patients was 41 ± 23.8 months. Demographics, pre-treatment calcium, PTH, and bone mineral density (BMD) were similar between the medical (N = 632) and surgical (N = 714) cohorts. Post-treatment calcium and PTH levels were significantly higher in the medical cohort (10.46 vs. 9.39, p < 0.01), (106.14 vs. 43.25, p = 0.001), respectively. Interestingly, the post-treatment PTH in the medical cohort increased when compared to pre-treatment (83.84 to 106.14). Patients in the medical cohort had lower BMD in lumbar (0.48 g/cm2; OR = 0.42, 95% CI = 0.21, 0.83), femoral (0.48; OR = 0.42, 95% CI = 0.29, 0.61), and hip (0.61; OR = 0.33, 95% CI = 0.13, 0.85). Incidences of fracture, nephrolithiasis, cardiovascular death, or overall mortality were not significantly different between the cohorts. CONCLUSIONS: The present study is the most comprehensive meta-analysis on mild pHPT to date. Our findings reflect that parathyroidectomy is the superior option in the treatment of mild pHPT patients as opposed to medical management.

Hashimoto's Thyroiditis: A Protective Factor against Recurrence in BRAF-Wild Type Differentiated Thyroid Carcinoma.

A recent work analyzing the concomitant factors BRAF mutation (risk factor) and Hashimoto's thyroiditis (HT) (protective factor) found that the presence of HT reduced lymph node metastasis in BRAF-mutated papillary thyroid carcinoma. Whether this notion is upheld with respect to disease recurrence and differentiated thyroid carcinoma (DTC), however, is unknown. We aimed to investigate the effect of underlying HT in DTC patients and its influence on recurrence with a specific emphasis in BRAF-mutated tumors. A total of 469 patients were included. Patients were stratified according to BRAF and HT status. Multivariate regression analysis was conducted to determine protective and risk factors of disease recurrence in patients with DTC. HT was associated with less-aggressive carcinomas including more frequent microcarcinomas (HT: 45.0% vs. no-HT: 34.0%, p = 0.02), less lymph node involvement (HT: 16.4% vs. no-HT: 26.1%, p = 0.02), and less disease recurrence (HT: 2.9% vs. no-HT: 11.9%, p = 0.002). BRAF mutation was also significantly associated with higher rates of lymph node involvement (BRAF-mutant: 41.9% vs. BRAF-wild type: 14.6%, p < 0.001) and almost two times the rate of recurrence (BRAF-mutant: 14.9% vs. BRAF-wild type: 6.5%, p = 0.004). Underlying HT was the only protective factor determined, reducing the odds of developing recurrence by 70% (HR: 0.30, 95%CI: 0.11-0.88). In the BRAF-wild type cohort, regression analysis continued to determine HT as a protective factor (p = 0.03). However, in the BRAF-mutant cohort, HT was no longer an independent protective factor (p = 0.20) against recurrence. Sub-group regression analysis, including PTC patients, similarly found HT as a protective factor only in BRAF-wild type patients (p = 0.039) and not BRAF-mutant (p = 0.627). The presence of underlying HT is associated with less aggressive tumors and is an independent protective factor against DTC recurrence, reducing the risk by 70%. HT remains a protective factor in BRAF-wild type carcinoma, but not in patients with BRAF-mutant carcinoma. HT may potentially be considered as a parameter which enhances American Thyroid Association patient risk stratification.

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.

Diagnostic Performance of Afirma and Interpace Diagnostics Genetic Testing in Indeterminate Thyroid Nodules: A Single Center Study.

Indeterminate thyroid nodules (ITN) represent 20-30% of biopsied nodules, with a 10-60% risk of malignancy. Molecular testing can stratify the risk of malignancy among ITNs, and subsequently reduce the need for unnecessary diagnostic surgery. We aimed to assess the performance of these molecular tests at a single institution. Patients with Bethesda III, IV, and V nodules with Afirma and Interpace Diagnostics genetic testing data from November 2013 to November 2021 were included. Three cohorts were formed, including GSC + XA, ThyGeNEXT + ThyraMIR, and GSC + GEC. Statistical analysis determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio (DOR), and accuracy of each type of testing. The PPV of nodules undergoing genetic testing by ThyGeNEXT + ThyraMIR (45.00%, 95%CI: 28.28-62.93%, p = 0.032) and GSC + XA (57.14%, 95%CI: 29.32-81.08%, p < 0.001) were superior to that of GEC + GSC (30.72%, 95%CI: 26.83-34.90%). The NPV was above 85% in all cohorts, suggesting overall suitable rule-out tests. The Afirma platform (GSC + XA) had the highest NPV at 96.97%. The overall accuracy for nodules undergoing ThyGeNEXT + ThyraMIR was 81.42% (95%CI: 73.01-88.11%, p < 0.001). A total of 230 patients underwent thyroidectomy, including less than 60% of each of the ThyGeNEXT + ThyraMIR and GSC + XA cohorts. Specifically, only 25% of patients in the GSC + XA cohort underwent surgery, considerably decreasing the rate of unnecessary surgical intervention. Sub-group analysis, including only patients with surgical pathology, found that PPV tended to be higher in the GSC + XA cohort, at 66.67% (95%CI: 37.28-87.06%), as compared to the ThyGeNEXT + ThyraMIR cohort, at 52.94% (95%CI: 35.25-69.92%). The Afirma genetic testing platform GSC + XA outperformed the other platforms with regards to both PPV and NPV and decreased the rate of surgery in patients with ITNs by 75%, significantly preventing unnecessary surgical intervention.