Importance Thyroid nodules are common, being detected in up to 65% of the general population. This is likely due to the increased use of diagnostic imaging for purposes unrelated to the thyroid. Most thyroid nodules are benign, clinically insignificant, and safely managed with a surveillance program. The main goal of initial and long-term follow-up is identification of the small subgroup of nodules that harbor a clinically significant cancer (≈10%), cause compressive symptoms (≈5%), or progress to functional disease (≈5%). Observations Thyroid function testing and ultrasonographic characteristics guide the initial management of thyroid nodules. Certain ultrasound features, such as a cystic or spongiform appearance, suggest a benign process that does not require additional testing. Suspicious sonographic patterns including solid composition, hypoechogenicity, irregular margins, and microcalcifications should prompt cytological evaluation. Additional diagnostic procedures, such as molecular testing, are indicated only in selected cases, such as indeterminate cytology (≈20%-30% of all biopsies). The initial risk estimate, derived from ultrasound and, if performed, cytology report, should determine the need for treatment and the type, frequency, and length of subsequent follow-up. Management includes simple observation, local treatments, and surgery and should be based on the estimated risk of malignancy and the presence and severity of compressive symptoms. Conclusions and Relevance Most thyroid nodules are benign. A diagnostic approach that uses ultrasound and, when indicated, fine-needle aspiration biopsy and molecular testing, facilitates a personalized, risk-based protocol that promotes high-quality care and minimizes cost and unnecessary testing.

https://jamanetwork.com/journals/jama/articlepdf/2673975/jama_Durante_2018_rv_180001.pdf

The Diagnosis and Management of Thyroid Nodules: A Review

Objective:To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy.Background:Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in th

The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults

Context Papillary thyroid microcarcinoma (PTMC) usually has an excellent prognosis. Objective To evaluate the three-dimensional structures of PTMCs, using serial neck ultrasonography (US) in patients under active surveillance. Design and setting A retrospective cohort study. Participants In total, 192 patients diagnosed with PTMC under active surveillance for >1 year were included in a median 30-month follow-up. Changes in tumor size were evaluated not only using the maximal tumor diameter but also the tumor volume. Results The median age of patients was 51.3 years and 145 patients (76%) were female. The median initial maximal tumor diameter and tumor volume were 5.5 mm and 48.8 mm3, respectively. The tumor size increased in 27 patients (14%); 23 patients showed a tumor volume increase >50% without a maximal diameter increase of ≥3 mm. The other four patients had both an increasing tumor volume and increasing maximal tumor diameter ≥3 mm. One patient (0.5%) had newly appeared cervical lymph node (LN) metastasis at 3 years after the initial diagnosis. There were no significant risk factors associated with increased tumor size, such as age, sex, or Hashimoto thyroiditis. Twenty-four patients (13%) underwent delayed thyroid surgery at a median of 31.2 months and seven (29%) had cervical LN metastasis on pathologic examination. Conclusion Some PTMCs could grow significantly after a relatively short period of active surveillance. We also found that the change in tumor volume was more sensitive to detect tumor progression than the change in the maximal tumor diameter.

Active Surveillance for Patients With Papillary Thyroid Microcarcinoma: A Single Center's Experience in Korea.

Role of molecular markers in thyroid nodule management: then and now.

Cancers are the group of diseases, which arise because of the uncontrolled behavior of some of the genes in our cells. There are possibilities of gene amplifications, overexpressions, deletions and other anomalies which might lead to the development and spread of cancer. One of the most dangerous ways to the cancers is the mutations of the genes. The mutated genes can start unstoppable proliferation of cells, their uncontrolled motility, protection from apoptosis, the DNA mutation enhancement as well as other anomalies, leading to the cancer. This review focuses on the genes, which are frequently mutated in various cancers and are known to be important in the advance and progression of colorectal cancer and melanoma, namely KRAS, NRAS and BRAF.

KRAS, NRAS and BRAF mutations in colorectal cancer and melanoma

This review is intended to provide an updated role of molecular genetics and various targeted therapies that have been developed to treat advanced stages of melanoma Because of the declining success in melanoma therapy, the curative treatment for advanced stage melanoma has been a challenge for clinicians Several mutations such as N-RAS, p53, BRAF including mutant-BRAF that lead to activation of kinase pathway, are implicated in the development of malignant melanoma However, the current literature depicts that the prognostic role of BRAF mutation in disease progression is still controversial While its higher level in advanced stage disease is associated with decreased overall survival (OS), some studies show that it failed to confer as an independent prognostic predictor of the disease This has also led researchers to accomplish newer therapeutic strategies that lead to improved disease-response and grant survival benefits Vemurafenib, a BRAF inhibitor agent, is one of the few available targeted therapies that is FDA approved and provides promising results in metastatic disease However, its resistance at an early stage is of great concern Recent implementation of combinational therapies including "targeted therapy", immunotherapy, and biological agents has appealed many researchers to define the adjunctive role of available therapies and their limitations in advanced stage and metastatic melanoma This commends the need for future multi-institutional studies to confirm the clinical validity of different therapeutic strategies on a large scale population

Impact of BRAF mutation status in the prognosis of cutaneous melanoma: an area of ongoing research

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.

/pdf/association-of-malignancy-prevalence-with-test-properties-3g8kpm0loq.pdf

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

Importance Reoperation for recurrent papillary thyroid cancer (PTC) can be associated with a high rate of complications and failure to provide lasting remission. Percutaneous ethanol injection (PEI) may be an effective nonsurgical management option for locally recurrent PTC. Objective This systematic analysis of the current literature compares the efficacy and complications related to PEI vs reoperative surgical intervention for treatment of locally recurrent PTC. Data Sources Original studies were identified using the keywords “thyroid/ethanol” and “recurrent thyroid cancer/repeat surgery.” Study Selection Studies evaluating reoperation or PEI for lymph node metastases in patients with primary surgery of total thyroidectomy with appropriate lymph node dissection where indicated were included in the analysis for both reoperation and PEI. Animal studies, single case reports, and studies with fewer than 10 lesions were excluded. Data Extraction and Synthesis Outcomes included interval to detection of recurrence, success and failure rates, recurrence rates, complication rates, and follow-up duration. Between-group outcome differences were calculated using random-effects models, and pooled data cross-tabulation and logistic regression analysis were used. Results In all, 945 publications were identified, and 27 studies met the inclusion criteria. There were no studies that directly compared the 2 treatment techniques. A total of 1617 patients were included in this analysis; 168 (11.4%) were treated with PEI, and 1449 (88.6%) were treated with reoperation. Reoperation was successful in 94.8% of cases compared with an 87.5% success rate for PEI (odds ratio [OR], 2.58; 95% CI, 1.55-4.31;P  Conclusions and Relevance High-quality, well-designed studies are needed to evaluate the feasibility of incorporating PEI into the treatment protocol of PTC. Although presently inferior to reoperation, PEI has the potential to be a widely accepted and effective nonsurgical treatment option for limited recurrent PTC in poor surgical candidates or patients seeking to avoid multiple reoperations.

/pdf/percutaneous-ethanol-injection-vs-reoperation-for-locally-487n0z7sgk.pdf

Percutaneous ethanol injection vs reoperation for locally recurrent papillary thyroid cancer: a systematic review and pooled analysis.

Recurrent laryngeal nerve (RLN) injury is one of the most common complications of thyroid surgery. Injury to the external branch of the superior laryngeal nerve is less obvious and affects the voice variably; however, it can be of great significance to professional voice users. Recent literature has led to an increase in the use of neuromonitoring as an adjunct to visual nerve identification during thyroid surgery. In our review of the literature, we discuss the application, efficacy and safety of neuromonitoring in thyroid surgery. Although intraoperative neuromonitoring (IONM) contributes to the prevention of laryngeal nerves injury, there was no significant difference in the incidence of RLN injury in thyroid surgery when IONM was used compared with visual identification alone. IONM use is recommended in high risk patients; however, there are no clear identification criteria for what constitutes “high risk”. There is no clear evidence that IONM decreases the risk of laryngeal nerve injury in thyroid surgery. However, continuous IONM provides a promising tool that can prevent imminent nerve traction injury by detecting decreased amplitude combined with increased latency.

Electrophysiological neuromonitoring of the laryngeal nerves in thyroid and parathyroid surgery: A review.

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.

Parisha Bhatia

Papers

Impact of BRAF mutation status in the prognosis of cutaneous melanoma: an area of ongoing research

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

Percutaneous ethanol injection vs reoperation for locally recurrent papillary thyroid cancer: a systematic review and pooled analysis.

Electrophysiological neuromonitoring of the laryngeal nerves in thyroid and parathyroid surgery: A review.

Remote access thyroid surgery.