Comparison of Secondary and Primary Thyroid Cancers: Patient Characteristics and Postoperative Outcomes: A Cross-Sectional Analysis of Patients with Primary and Secondary Thyroid Cancers.

BACKGROUND: Secondary thyroid cancer is believed to lead to a more aggressive clinical course than primary thyroid cancer. We aim to examine the difference between primary and secondary thyroid cancer in terms of patient characteristics and perioperative outcomes at the national level. METHODS: A cross-sectional study utilizing the Nationwide Inpatient Sample database for 2003-2010 was merged with County Health Rankings Data. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to identify adult patients with thyroid cancer. RESULTS: A total of 21,581 discharge records were included. Overall, 16,625 (77.0 %) patients had primary cancer, while the rest (23.0 %) had secondary cancer. Younger (<45 years) and older (>65 years) patients, males, and those of White or Hispanic background were more likely to have secondary cancers (p < 0.05 each). The prevalence of secondary cancer was higher in communities of low health risk (24.0 % vs. 21.1 %; p < 0.024). Secondary cancer was more likely to be managed by total thyroidectomy (odds ratio [OR] 2.40, 95 % CI 2.12-2.73) and to require additional radical neck dissection (OR 12.51, 95 % CI 10.98-14.25). Patients with secondary thyroid cancers were at higher risk of postoperative complications (p < 0.01 each). The cost of secondary cancer management was significantly higher than primary cancer (US$12,449.00 ± 302.07 vs. US$7848.12 ± 149.05; p < 0.001). However, compared with intermediate-volume surgeons, the complication risk was lower for high-volume (OR 0.47, 95 % CI 0.24-0.92; p = 0.026). CONCLUSIONS: Secondary thyroid cancer is associated with a higher risk of perioperative complications and higher cost and distinct demographic profile. Patients managed by higher-volume surgeons were less likely to experience disadvantageous outcomes.

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.

Status Epilepticus in Creutzfeldt-Jakob Disease: A Case Report of an Unusual Presentation.

Although non-prion neurodegenerative illnesses are the main causes of rapidly progressive dementia (RPD), a case of RPD should be evaluated for Creutzfeldt-Jakob disease (CJD), a kind of prion disease. We describe a 71-year-old man who first displayed a lack of coordination before developing focal seizures accompanied by myoclonic jerks as well as left hemibody weakness and incoordination. As part of the additional diagnostic workup, cerebrospinal fluid (CSF) analyses, 72 hours of prolonged electroencephalogram (EEG) monitoring, and additional brain imaging were obtained. Cortical ribboning was seen in the magnetic resonance imaging (MRI) of the brain, protein 14-3-3 test in the CSF was normal, lateralized and generalized periodic discharges were seen on the EEG. After the patient was examined for additional causes, such as autoimmune encephalitis and seizures, the diagnosis of likely CJD was made. Ultimately, an autopsy was performed and confirmed the diagnosis of definitive CJD.

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.

Vanishing tumors of thyroid: histological variations after fine needle aspiration.

BACKGROUND: Fine needle aspiration (FNA) can lead to changes that extensively replace cytological confirmed thyroid lesions. These lesions, so called "vanishing tumors" can be diagnostically challenging to pathologists and therapeutically challenging for endocrinologists and surgeons. We performed a retrospective analysis to identify these tumors. METHODS: Data of 656 patients referred for thyroid surgery was reviewed. Patients with suspicious lesions on neck ultrasound (US) underwent FNA. We compared FNA cytological and surgical pathological findings to identify vanishing tumors. FNA-induced changes such as cystic degeneration, hemorrhage, calcification, cholesterol crystals, fibrosis and granulation tissue were identified. RESULTS: Seventeen patients (2.5%) were identified with vanishing tumors. FNA cytology was indeterminate in seven (41.1%) and benign in ten (58.8%) patients. Surgical pathology in all nodules showed regressive changes partially or entirely replacing the tumor. The mean size of vanishing tumors was 2.4±1.5 cm in greatest dimension. Seven nodules (41.1%) were entirely replaced while remaining ten nodules showed partial replacement of tumors. Three (17.6%) nodules had focal areas of optically clear nuclei suspicious of papillary thyroid carcinoma (PTC); one showed an additional focus of follicular neoplasm (FN) of uncertain malignant potential. CONCLUSIONS: FNA-induced changes can lead to obliteration of nodules rendering pathological diagnosis with no evidence of confirmed lesions. Pathologists and surgeons should be aware of this challenging scenario.

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

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.

Robotic transaxillary and retroauricular parathyroid surgery.

Current advancement in robotic surgery has provided a safe, precise, 3-dimensional (3D) magnified dissection for parathyroid surgery without the need for CO2 insufflation, and with a better cosmetic outcome due to an invisible scar in the axillary or retroauricular region. Preoperative imaging studies that assist in the localization of lesions have been key elements in patients' selection for targeted parathyroid surgery.

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

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.

Diagnostic potential of ancillary molecular testing in differentiation of benign and malignant thyroid nodules.

Fine needle aspiration (FNA) cytology, being the mainstay to diagnose thyroid nodules, does not provide definitive results in a subset of patients. The use of molecular markers testing has been described as a useful aid in differentiation of thyroid nodules that present with an indeterminate cytodiagnosis. Molecular tests, such as the Afirma gene classifier, mutational assay and immunohistochemical markers have been increasingly used to further increase the accuracy and defer unnecessary surgeries for benign thyroid nodules. However, in light of the current literature, their emerging roles in clinical practice are limited due to financial and technical limitations. Nevertheless, their synergistic implementation can predict the risk of malignancy and yield an accurate diagnosis. This review discusses the clinical utility of various molecular tests done on FNA indeterminate nodules to avoid diagnostic thyroidectomies and warrant the need of future multi-Institutional studies.

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.

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

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 < .001). The recurrence rates for PEI and reoperation at the site of the treated lesion or elsewhere in the neck were also similar (OR, 1.07; 95% CI, 0.65-1.77; P = .78). Reoperation was associated with a 3.5% pooled risk of complications, while PEI incurred a pooled risk of 1.2% (OR, 2.9; 95% CI, 0.72-12.3; P = .08). However, most studies did not report routine preoperative and postoperative laryngoscopies, an evaluation needed for accurate neural complication analysis associated with each procedure. 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.

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.

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.

Cutaneous Metastases from Primary Hepatobiliary Tumors as the First Sign of Tumor Recurrence following Liver Transplantation.

Cutaneous metastasis from hepatobiliary tumors is a rare event, especially following liver transplantation. We report our experience with two cases of cutaneous metastases from both hepatocellular carcinoma and mixed hepatocellular/cholangiocarcinoma following liver transplantation, along with a review of the literature.