Chemotherapeutic potential of betanin/capecitabine combination targeting colon cancer: experimental and bioinformatic studies exploring NFκB and cyclin D1 interplay.

Introduction: Betanin (C24H26N2O13) is safe to use as food additives approved by the FDA with anti-inflammatory and anticancer effects in many types of cancer cell lines. The current experiment was designed to test the chemotherapeutic effect of the combination of betanin with the standard chemotherapeutic agent, capecitabine, against chemically induced colon cancer in mice. Methods: Bioinformatic approach was designed to get information about the possible mechanisms through which the drugs may control cancer development. Five groups of mice were assigned as, (i) saline, (ii) colon cancer, (iii) betanin, (iv) capecitabine and (v) betanin/capecitabine. Drugs were given orally for a period of six weeks. Colon tissues were separated and used for biological assays and histopathology. Results: In addition, the mRNA expression of TNF-α (4.58-fold), NFκB (5.33-fold), IL-1ß (4.99-fold), cyclin D1 (4.07-fold), and IL-6 (3.55-fold) and protein levels showed several folds increases versus the saline group. Tumor histopathology scores in the colon cancer group (including cryptic distortion and hyperplasia) and immunostaining for NFκB (2.94-fold) were high while periodic-acid Schiff staining demonstrated poor mucin content (33% of the saline group). These pathologic manifestations were reduced remarkably in betanin/capecitabine group. Conclusion: Collectively, our findings demonstrated the usefulness of betanin/capecitabine combination in targeting colon cancer and highlighted that betanin is a promising adjuvant therapy to capecitabine in treating colon cancer patients.

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.

Survival Outcomes of Medullary Thyroid Cancer With and Without Amyloid Deposition.

OBJECTIVE: Amyloid deposition within tumor stroma is a distinctive histologic feature of medullary thyroid cancer (MTC). However, its prognostic significance remains uncertain. We aimed to elucidate the impact of amyloid status on survival outcomes in a large cohort. METHODS: The Surveillance, Epidemiology, and End Results registry was queried to identify patients diagnosed with MTC from 2000 to 2019. Patients with amyloid-positive (International Classification of Diseases for Oncology, third edition code 8345/3) and amyloid negative (International Classification of Diseases for Oncology, third edition code 8510/3) tumors were analyzed. Overall and disease-specific survival were compared between matched cohorts using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Of the 2526 MTC patients, 511 of which were amyloid-positive and 2015 that were amyloid negative. Amyloid-positive patients displayed lower T stage (T3/4: 28% vs 85%, P < .001) and less extrathyroidal extension (11.3% vs 81.6%, P < .001). No difference in distant metastasis rate was observed between groups (14.5% vs 14.4%, P = .98). However, amyloid-positive patients showed a tendency for distal lymph node metastasis (1.2% vs 0.3%, P = .020). On univariate analysis, amyloid-positive status showed comparable overall survival times (mean 172.2 vs 177.8 months, P = .17), but a trend toward worse cancer-specific survival (hazard ratios [HR] = 1.31, 95% CI = 0.99-1.71, P = .051). After adjusting for covariates, amyloid deposition did not independently predict overall (HR = 1.15, 95% CI = 0.91-1.47, P = .25) or cancer-specific survival (HR = 1.30, 95% CI = 0.96-1.77, P = .09). Initiating therapy later than 1 month following diagnosis was associated with worse overall survival (HR = 1.25, 95% CI = 1.02-1.54, P = .029). CONCLUSIONS: The presence of amyloid in MTC paradoxically associates with lower T stage yet exhibits a trend toward worse cancer-specific mortality. Amyloid deposition alone does not independently influence prognosis. Delayed treatment adversely impacted overall survival.

Elucidating the link between thyroid cancer and mercury exposure: a review and meta-analysis.

Mercury (Hg) is a widely distributed and bioavailable metal of public health concern, with many known human toxicities, but data regarding mercury's influence on thyroid cancer (TC) is scarce. Mercury is known to impact several molecular pathways implicated in carcinogenesis, and its proclivity for bioaccumulation in the thyroid suggests a potential modulatory effect. We conducted a literature/systematic review of studies between 1995-2022 intending to define better and establish relationships between these two entities, congregate the evidence for mercury's potential role in thyroid carcinogenesis, and identify populations of interest for further study. Insufficient evidence precludes definitive conclusions on dietary mercury as a TC risk factor; however, several common mechanisms affected by mercury are crucial for TC development, including biochemical, endocrine, and reactive oxygen species effects. Quantitative analysis revealed associations between TC risk and mercury exposure. In three mercury studies, average urine levels were higher in TC patients, with a mean difference of 1.86 µg/g creatinine (95% CI = 0.32-3.41). In two studies investigating exposure to elevated mercury levels, the exposed group exhibited a higher risk of developing TC, with a relative risk of 1.90 (95% CI = 1.76-2.06). In three thyroid tissue studies, mercury levels (ppm) were higher in TC patients, averaging 0.14 (0.06-0.22) in cancerous cases (N = 178) and 0.08 (0.04-0.11) in normal thyroids (N = 257). Our findings suggest an association between mercury exposure and TC risk, implying a possible predisposing factor. Further research is necessary to reveal the clinical relevance of dietary and environmental mercury exposures in TC pathogenesis.

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.

Survival benefits of extensive surgery in patients with papillary thyroid microcarcinoma.

BACKGROUND: Despite the guidelines recommending thyroid lobectomy, many papillary thyroid microcarcinoma (PTMC) patients still undergo total thyroidectomy. PTMC's optimal treatment remains unclear. We aimed to determine whether total thyroidectomy improves outcomes compared to less extensive surgery. METHODS: We analyzed 6064 PTMC adult patients from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019) who underwent either total thyroidectomy (n â€‹= â€‹3652) or less extensive surgery (n â€‹= â€‹2412). Endpoints were overall survival, cancer-specific survival, and recurrence. RESULTS: Total thyroidectomy patients had a 5.2 â€‹% mortality rate versus 8.1 â€‹% with less extensive surgery. Recurrence occurred in 1 (0.03 â€‹%) total thyroidectomy patient compared to 24 (1.0 â€‹%) less extensive surgery patients (HR 0.07, p â€‹= â€‹0.01). Median survival was 8.1 years for total thyroidectomy versus 8.8 years for less extensive surgery. Overall survival favored total thyroidectomy (p â€‹= â€‹0.001) but cancer-specific survival did not differ. CONCLUSION: Although total thyroidectomy may not improve cancer-specific survival, it lowers recurrence risk and confers an overall survival advantage for PTMC patients. These findings may help guide surgical decisions.

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.

Radiofrequency ablation of benign thyroid nodules: A prospective, multi-institutional North American experience.

BACKGROUND: Radiofrequency ablation for benign thyroid nodules aims to achieve a volume reduction rate of ≥50%. However, factors that predict treatment success have not been defined in a large-scale study. METHODS: A prospective cohort study of biopsy-proven benign thyroid nodules treated with radiofrequency ablation at 3 institutions was performed. Patient demographics, nodule sonographic features, procedural data, and nodule volume reduction were evaluated. Binary logistic regression analysis was performed to identify features associated with treatment response. RESULTS: A total of 620 nodules were analyzed. The pooled median volume reduction rate at 12 months was 70.9% (interquartile range 52.9-86.6). At 1 year follow-up, 78.4% of nodules reached treatment success with a volume reduction rate ≥50%. The overall complication rate was 3.2% and included temporary voice changes (n = 14), vasovagal episodes (n = 5), nodule rupture (n = 3), and lightheadedness (n = 2). No permanent voice changes occurred. Four patients developed postprocedural hypothyroidism. Large baseline nodule volume (>20 mL) was associated with a lower rate of successful volume reduction (odds ratio 0.60 [0.37-0.976]). Large nodules achieved treatment success by 12-month follow-up at a rate of 64.5%, compared with 81.4% for small nodules and 87.2% for medium nodules. CONCLUSION: To our knowledge, this is the largest North American cohort of patients with benign thyroid nodules treated with radiofrequency ablation. Overall, radiofrequency ablation was an effective treatment option with a low risk of procedural complications. Large volume nodules (>20 mL) may be associated with a lower rate of successful reduction with radiofrequency ablation treatment.

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.

Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer.

Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers in thyroid cancer progression and metastasis. However, their combined evaluation and clinical utility as a unified prognostic marker across diverse thyroid cancer subgroups remain unexplored. We investigated the diagnostic and prognostic value of the MMP9/miR-145 ratio in thyroid cancer, hypothesizing it may overcome inter-patient heterogeneity and serve as a versatile biomarker regardless of genetic mutations or autoimmune status. MMP9 and miR-145 expressions were analyzed in 175 paired papillary thyroid cancer (PTC) and normal tissues. Plasma levels were assessed perioperatively and longitudinally over 12-18 months in 86 matched PTC patients. The associations with clinicopathological parameters and patient outcomes were evaluated. MMP9 was upregulated, and miR-145 downregulated in cancer tissues, with a median MMP9/miR-145 ratio 17.6-fold higher versus controls. The tissue ratio accurately diagnosed thyroid malignancy regardless of BRAF mutation or Hashimoto's thyroiditis status, overcoming genetic and autoimmune heterogeneity. A high preoperative circulating ratio predicted aggressive disease features, including lymph node metastasis, extrathyroidal extension, progression/relapse, and recurrence. Although the preoperative plasma ratio was elevated in patients with unfavorable outcomes, it had limited utility for post-surgical monitoring. In conclusion, the MMP9/miR-145 ratio is a promising biomarker in PTC that bridges genetic and immunological variabilities, enhancing preoperative diagnosis and prognostication across diverse patient subgroups. It accurately stratifies heterogenous cases by aggressiveness. The longitudinal trends indicate decreasing applicability for post-thyroidectomy surveillance. Further large-scale validation and protocol standardization can facilitate clinical translation of the MMP9/miR-145 ratio to guide personalized thyroid cancer management.

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.

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.

Navigating Choices: Determinants and Outcomes of Surgery Refusal in Thyroid Cancer Patients Using SEER Data.

With thyroid cancer being a prevalent endocrine cancer, timely management is essential to prevent malignancy and detrimental outcomes. Surgical intervention is a popular component of the treatment plan, yet patients often refuse to undergo such procedures even if clinicians explicitly recommend them. This study gathers data from the Surveillance, Epidemiology, and End Results database (2000-2019) to learn more about the sociodemographic factors that predict the likelihood of surgical intervention. A total of 176,472 patients diagnosed with either papillary or follicular thyroid cancer were recommended surgery, of which 470 were refused. Cancer-specific mortality and overall mortality were determined with the Kaplan-Meier method and univariate and multivariate Cox proportional hazards regression model. Mortality rates for patients who delayed surgery (≥4 months vs. <4 months) were determined using similar methods. The findings reveal that surgical delay or refusal increased overall mortality. The surgical refusal was associated with increased thyroid cancer-specific mortality. However, the impact on thyroid cancer-specific mortality for those who delay surgery was not as pronounced. Significant sociodemographic determinants of surgical refusal included age greater than or equal to 55 years, male sex, being unmarried, race of Asian and Pacific Islander, and advanced tumor staging. The results underscore the importance of patient education, shared decision-making, and access to surgical interventions to optimize outcomes in thyroid cancer management.