Parisha Bhatia

Association of Malignancy Prevalence With Test Properties and Performance of the Gene Expression Classifier in Indeterminate Thyroid Nodules

Importance It is crucial for clinicians to know the malignancy prevalence within each indeterminate cytologic category to estimate the performance of the gene expression classifier (GEC). Objective To examine the variability in the performance of the GEC. Design, Setting, and Participants This retrospective cohort study of patients with Bethesda category III and IV thyroid nodules used single-institution data from January 1, 2013, through February 29, 2016. Expected negative predictive value (NPV) was calculated by adopting published sensitivity and specificity. Observed NPV was calculated based on the true-negative rate. Outcomes were compared with pooled data from 11 studies published January 1, 2010, to January 31, 2016. Results A total of 145 patients with 154 thyroid nodules were included in the study (mean [SD] age, 56.0 [16.2] years; 106 females [73.1%]). Malignancy prevalence was 45%. On the basis of this prevalence, the expected NPV is 85% and the observed NPV is 69%. If the prevalence is assumed to be 25%, the expected NPV would be 94%, whereas the observed NPV would be 85%. Pooled data analysis of 11 studies comprising 1303 participants revealed a malignancy prevalence of 31% (95% CI, 29%-34%) and a pooled NPV of 92% (95% CI, 87%-96%). Conclusions and Relevance In this study, variability in the performance of the GEC was not solely a function of malignancy prevalence and may have been attributable to intrinsic variability of the test sensitivity and specificity. The utility of the GEC in practice is elusive because of this variability. A better definition of the GEC’s intrinsic properties is needed.

Stem cell biology in thyroid cancer: Insights for novel therapies

Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.

Remote access thyroid surgery

Robot assisted thyroid surgery has been the latest advance in the evolution of thyroid surgery after endoscopy assisted procedures. The advantage of a superior field vision and technical advancements of robotic technology have permitted novel remote access (trans-axillary and retro-auricular) surgical approaches. Interestingly, several remote access surgical ports using robot surgical system and endoscopic technique have been customized to avoid the social stigma of a visible scar. Current literature has displayed their various advantages in terms of post-operative outcomes; however, the associated financial burden and also additional training and expertise necessary hinder its widespread adoption into endocrine surgery practices. These approaches offer excellent cosmesis, with a shorter learning curve and reduce discomfort to surgeons operating ergonomically through a robotic console. This review aims to provide details of various remote access techniques that are being offered for thyroid resection. Though these have been reported to be safe and feasible approaches for thyroid surgery, further evaluation for their efficacy still remains.

The utility of molecular markers in pre-operative assessment of thyroid nodules

The pre-operative diagnosis of thyroid tumors is determined by gold standard fine needle aspiration (FNA) biopsy. This has been widely accepted and offers the most cost-effective approach for evaluation of thyroid nodules. However, its diagnostic accuracy can pose a challenging scenario to surgeons. These diagnostic difficulties may subject patients to unnecessary thyroidectomies for benign thyroid nodules. Thus, additional molecular tests are needed to improve the sensitivity and specificity of FNA. The role of molecular markers is being proposed to predict the type and risk of malignancy to abate the need for diagnostic thyroidectomies. This review discusses their utility and validity in pre-operative diagnosis of thyroid nodules and how these markers can enhance the accuracy of FNA cytology.

BRAF Testing in Multifocal Papillary Thyroid Carcinoma

Background. BRAF V600E mutation is associated with poor prognosis in patients with papillary thyroid carcinoma (PTC). PTC is often multifocal, and there are no guidelines on how many tumors to test for BRAF mutation in multifocal PTC. Methods. Fifty-seven separate formalin-fixed and paraffin-embedded PTCs from twenty-seven patients were manually macrodissected and tested for BRAF mutation using a commercial allele-specific real-time polymerase chain reaction-based assay (Entrogen, Woodland Hills, CA). Data related to histologic characteristics, patient demographics, and clinical outcomes were collected. Results. All mutations detected were BRAF V600E. Seventeen patients (63%) had concordant mutation status in the largest and second-largest tumors (i.e., both were positive or both were negative). The remaining ten patients (37%) had discordant mutation status. Six of the patients with discordant tumors (22% overall) had a BRAF-negative largest tumor and a BRAF-positive second-largest tumor. No histologic feature was found to help predict which cases would be discordant. Conclusions. Patients with multifocal PTC whose largest tumor is BRAF-negative can have smaller tumors that are BRAF-positive. Therefore, molecular testing of more than just the dominant tumor should be considered. Future studies are warranted to establish whether finding a BRAF mutation in a smaller tumor has clinical significance.

Percutaneous Ethanol Injection Treatment, Novel Solution for the Challenge of Recurrent Thyroid Pathology: A Review

Introduction: Thyroid nodules are among the most common endocrine complaints in the United States. With increasing incidence of differentiated thyroid carcinoma there has been a widespread interest in development of minimally invasive treatments such as percutaneous ethanol injection (PEI) to manage thyroid pathology. In our review of published literatures, we discuss the application of ethanol injection for treatment of benign thyroid nodules and its efficacy in treating locally recurrent papillary thyroid carcinoma. Evolving treatment roles of PEI: PEI has been most successful at treating recurrent cystic nodules. In hyperfunctioning nodules, PEI is indicated for patients who are poor surgical and radioiodine therapy candidates. Initial trials of PEI in metastatic lymph nodes in papillary thyroid carcinoma have yielded promising therapeutic results with only minor side effects. PEI does not remove the option of future radio-frequency ablation or surgery which may become necessary in some cases. Conclusion: In our opinion, percutaneous ethanol injection proves to be a superior treatment modality for benign thyroid nodules showing markedly higher success in cystic nodules. Its safety and efficacy in treating recurrent papillary thyroid carcinoma is significant.