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.

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.

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.

Drug-induced olfactory and gustatory dysfunction: Analysis of FDA adverse events reporting system.

OBJECTIVES: With the COVID-19 pandemic, there is growing interest and research in olfactory and gustatory dysfunction (OGD). Drug-induced dysfunction is an often overlooked etiology. While several medications include smell or taste disturbance as a side effect, there are no publications describing which medications are most frequently implicated. We aim to describe the patterns of these adverse drug reactions (ADRs) using the FDA Adverse Events Reporting System (FAERS). METHODS: The FAERS database was queried from 2011 to 2021 for terms describing ADRs related to OGD. Terms included anosmia, hyposmia, olfactory test abnormal, olfactory nerve disorder, hallucination olfactory, parosmia, ageusia, hypogeusia, dysgeusia, and taste disorder. We identified the top reported medications associated with general smell dysfunction, general taste dysfunction, reduced smell, and altered smell. RESULTS: From 2011 to 2021, 16,091 ADRs were reported with OGD, of which13,641 (84.8%) and 2,450 (15.2%) were associated with gustatory and olfactory reactions, respectively. Zinc products (370 reports) and fluticasone propionate (214) were most commonly associated with olfactory dysfunction, specifically reduced olfaction. Varenicline (24) and fluticasone propionate (23) were most commonly associated with altered smell. Lenalidomide (490) and sunitinib (468) were most commonly associated with gustatory dysfunction. Antineoplastic and immunomodulating medications accounted for 21.6% and 36.3% of olfactory and gustatory ADRs, respectively. Among this category, immunoglobulin drugs were the most commonly associated with OGD ADRs. CONCLUSION: Gustatory dysfunction is more commonly reported ADR compared with olfactory dysfunction. Immunologic/rheumatologic medications are the leading culprit of reported OGD. With increasing numbers of patients presenting to otolaryngologists for OGD, it is important to consider drug-induced etiology. LEVEL OF EVIDENCE: III.

A miRNA-Based Prognostic Model to Trace Thyroid Cancer Recurrence.

Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs may be associated with PTC recurrence and metastasis. Public databases such as TCGA and GEO were utilized for data sourcing and external validation, respectively, and miR-seq results were validated using quantitative real-time PCR (qRT-PCR). We found miR-145 to be significantly downregulated in tumor tissues and blood. Deregulation was significantly related to clinicopathological features of PTC patients including tumor size, lymph node metastasis, TNM stage, and recurrence. In silico data analysis showed that miR-145 can negatively regulate multiple genes in the TC signaling pathway and was associated with cell apoptosis, proliferation, stem cell differentiation, angiogenesis, and metastasis. Taken together, the current study suggests that miR-145 may be a biomarker for PTC recurrence. Further mechanistic studies are required to uncover its cellular roles in this regard.

Latency Trend Analysis as a Guide to Screening Malignancy Survivors for Second Primary Thyroid Cancer.

Primary cancer survivors have a higher risk of developing second primary thyroid cancer (SPTC). Patients with SPTC who survived primary malignancies, diagnosed from 1975 to 2016, were identified from the Surveillance, Epidemiology, and End Results (SEER) database (SEER 18 Registry). A total of 33,551 cancer cases were enrolled in the final analysis. Individuals with a primary malignancy were at a significant 90% increased risk of developing SPTC (SIR = 1.90, 95%CI = 1.86−1.93, p < 0.05) compared to the general population. More than half (54.7%) of SPTC diagnoses were made in the first three years after primary cancer diagnosis, and the most aggressive presentations of SPTC occurred within the first year following malignancy. A latency trend analysis identified persistent high risk for development of SPTC after diagnosis of lymphoma, leukemia, soft tissue tumors, kidney, breast, and uterine cancer; elevated 10-year risk for most cancers such as salivary gland, melanoma, stomach, lung, colon, ovarian, pancreas, prostate, and bladder; and high 5-year risk after cancers such as larynx, oral, orbit, bone, small intestine, and liver. Our latency period model identifying risk according to each type of primary cancer may aid clinicians in identifying at-risk patients to be screened for thyroid cancer and guide them in developing a surveillance plan according to the latency period attributed to a patient's primary cancer.

Advanced Computed Tomographic Localization Techniques for Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

Importance: Emerging computed tomographic (CT) imaging techniques for the localization of primary hyperparathyroidism (PHPT) may be superior to the current imaging standard, thus necessitating a critical review and pooling of available evidence. Objective: Primary hyperparathyroidism requires accurate imaging to guide definitive surgical management. Advanced techniques including 4-dimensional computed tomographic (4D-CT) scan have been investigated over the past decade. We sought to evaluate the efficacy of these emerging imaging techniques through pooled analysis of the existing evidence. Data Sources: PubMed, Embase, and Web of Science databases were queried for original English articles without any restrictions on date. Study Selection: We included comparative observational studies but excluded animal studies, case reports, and case series. Overall, 353 abstracts were screened independently by 2 investigators along with a third reviewer to resolve conflicts. A total of 26 full-text articles were included in this review. Data Extraction and Synthesis: This review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data was independently extracted by 2 investigators and subsequently pooled into a meta-analysis using a random-effects model. Main Outcomes and Measures: Measures of imaging diagnostic performance such as sensitivity, specificity, positive predictive value, and negative predictive value were the primary outcomes of interest. Results: Overall, of 34 articles screened, 26 met criteria for qualitative synthesis, and 23 of these were appropriate for meta-analysis. Of the 26 studies included, there were 5845 patients, of which 4176 were women (79.2%). The average of mean ages reported in 23 studies was 60.9 years. Meta-analysis in all patients with PHPT revealed pooled sensitivity that was greater with 4D-CT (81%; 95% CI, 77%-84%; I2 = 88%) compared with the current first-line modality of sestamibi-single-photon emission CT (SPECT/CT) (65%; 95% CI, 59%-70%; I2 = 93%). For patients with recurrent PHPT requiring reoperation, 4D-CT pooled sensitivity was 81% (95% CI, 64%-98%; I2 = 93%) in contrast to 53% (95% CI, 35%-71%; I2 = 81%) for sestamibi-SPECT/CT. The overall quality of the 26 studies was moderate with a median (range) Methodological Index for Nonrandomized Studies score for all included studies of 15.5 (13-19). Conclusions and Relevance: The findings of this systematic review and with meta-analyses of numerous studies from the past decade suggest that the 4D-CT can be more sensitive and specific than sestamibi-SPECT/CT in localizing PHPT. More research is needed to determine the clinical significance of this improvement in localization.