Surgery for nonlocalizing hyperparathyroidism in high volume center.

BACKGROUND: Patients with nonlocalizing hyperparathyroidism pose a significant challenge to surgeons when undergoing neck exploration for parathyroidectomy. METHODS: We evaluated 536 patients that had parathyroidectomy for primary hyperparathyroidism (PHPT) from 2005 to 2018 at a single tertiary academic center, and 155 (29%) had standard nonlocalizing preoperative imaging (negative ultrasound and sestamibi scans). RESULTS: There were a total of 102 (66%) non-ectopic single adenomas in the nonlocalizing group and 325 (85%) single adenomas in the localizing group. There was no significant difference (p = 0.09) in adenoma quadrant between localizing and nonlocalizing single adenomas, but the most common location in both groups was right inferior. Patients with nonlocalizing scans were more likely to have double adenomas (21% vs. 9%, p < 0.001), ectopic glands (10% vs. 5%, p = 0.052), and multi-gland disease (13% vs. 8%, p = 0.002). CONCLUSION: Nonlocalizing PHPT patients experienced similar cure and complication rates as localizing PHPT, but required more bilateral explorations and increased operative time.

Regulatory and Interacting Partners of PDLIM7 in Thyroid Cancer.

Enigma protein, encoded by the PDLIM7 gene, is overexpressed in thyroid cancer in a stage-dependent manner, suggesting a potential involvement in the initiation and progression of thyroid cancer. The Enigma interacts with several cellular pathways, including PI3K/AKT, MDM2, and BMP-1. The Enigma is regulated by microRNAs. Specifically, we showed that the Enigma protein upregulation corresponds to the downregulation of Let-7 family genes. There is limited research on the interactions and regulation of the Enigma with other proteins/genes in thyroid cancer tissues, indicating a gap in current knowledge. Our aim is to establish the Enigma as a biomarker. We also aim to study the interacting partners of the Enigma signaling pathways and their probable miRNA regulation in thyroid cancer progression. Using Western blotting, densitometric analysis, immunoprecipitation (IP), and reverse IP, we detected the protein expression and protein-protein interactions in the corresponding papillary thyroid carcinomas (PTCs). Utilizing real-time qPCR assay and Pearson's correlation test, we highlighted the correlation between PDLIM7 and Let-7g gene expression in the same tissues. The results showed the differential upregulations of the Enigma protein in different stages of PTCs compared to benign tissues along with AKT, VDR, BMP-1, and MDM2 proteins. Loss of DBP was observed in a subset of PTCs. Strong interactions of the Enigma with PI3K/AKT and MDM2 were noted, along with a weaker BMP-1 interaction. Pearson's correlation coefficient analysis between PDLIM7 and let-7g gene expression was significant (p < 0.05); however, there was a weak inverse correlation (r = -0.27). The study suggests the potential utility of the PDLIM7-qPCR assay as a biomarker for thyroid cancer. The Enigma's interactions with key signaling pathways may provide valuable insights into the development of thyroid cancer. The study contributes to understanding the molecular mechanisms involving the Enigma protein in thyroid cancer and highlights its potential as a biomarker.

Prevalence of Occult Central Lymph Node Metastasis by Tumor Size in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: While papillary thyroid carcinoma (PTC) is associated with high occult central neck metastasis (CNM) rates, prophylactic central neck dissection (pCND) is controversial. This meta-analysis aims to look at the occult CNM rate according to tumor size. METHODS: A literature search was conducted in PubMed from inception to April 2023. Inclusion criteria were primary studies that determined occult CNM rates in cN0 PTC by tumor size. Heterogeneity, influential case diagnostics, and proportion data were evaluated with Cochran's Q-test, Baujat plots and Forest plots, respectively. RESULTS: Fifty-two studies were included in this meta-analysis. The findings demonstrated an occult CNM rate of 30.3% for tumors ≤ 5 mm, 32.7% for tumors ≤ 1 cm, 46.0% for tumors between 1 and 2 cm, 43.1% for tumors between 2 and 4 cm, and 61.2% for tumors > 4 cm. The heterogeneity of each study group was high, though no publication bias was noted. While there was a trend towards increased occult CNM rates with larger tumors, comparisons between different size cutoffs varied in significance. CONCLUSION: This comprehensive review affirms that occult CNM is high and that an ipsilateral pCND can be justified in all PTC patients for accurate differentiation between Stage I and Stage II disease and its clinical implications.

Targeting Tumor Microenvironment Akt Signaling Represents a Potential Therapeutic Strategy for Aggressive Thyroid Cancer.

Effects of the tumor microenvironment (TME) stromal cells on progression in thyroid cancer are largely unexplored. Elucidating the effects and underlying mechanisms may facilitate the development of targeting therapy for aggressive cases of this disease. In this study, we investigated the impact of TME stromal cells on cancer stem-like cells (CSCs) in patient-relevant contexts where applying in vitro assays and xenograft models uncovered contributions of TME stromal cells to thyroid cancer progression. We found that TME stromal cells can enhance CSC self-renewal and invasiveness mainly via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. The disruption of Akt signaling could diminish the impact of TME stromal cells on CSC aggressiveness in vitro and reduce CSC tumorigenesis and metastasis in xenografts. Notably, disrupting Akt signaling did not cause detectable alterations in tumor histology and gene expression of major stromal components while it produced therapeutic benefits. In addition, using a clinical cohort, we discovered that papillary thyroid carcinomas with lymph node metastasis are more likely to have elevated Akt signaling compared with the ones without metastasis, suggesting the relevance of Akt-targeting. Overall, our results identify PI3K/Akt pathway-engaged contributions of TME stromal cells to thyroid tumor disease progression, illuminating TME Akt signaling as a therapeutic target in aggressive thyroid cancer.

Outcomes of Early Versus Delayed Completion Thyroidectomy for Malignancy.

PURPOSE: To determine whether time interval between hemi-thyroidectomy and subsequent completion thyroidectomy impacts outcomes. METHODS: Retrospective review of 68 patients having completion thyroidectomy from August 2012 to December 2019. Patients were separated into two groups based on the time interval between surgeries: early (≤10 days) or delayed (≥90 days). RESULTS: Patients who underwent delayed completion thyroidectomy (n = 17) had significantly higher rates of hypocalcemia and/or hypoparathyroidism (P = .03) and higher rates of requiring postoperative hospitalization (P=.07) compared to those who underwent early completion thyroidectomy (n = 51). Delayed completion had significantly lower risk of developing one or more of dysphonia, dysphagia, or vocal cord paresis postoperatively (P=.02). No patients developed hematoma or wound infection. CONCLUSIONS: Delayed completion thyroidectomy is associated with increased rates of hypocalcemia, but lower rates of dysphonia and dysphagia. Given the low risk of long-term complications in both groups, it may be beneficial to perform completion thyroidectomy early in order to expedite cancer treatment.

Incidence of Dysphonia and Dysphagia Exceeds Recurrent Laryngeal Nerve Injury During Thyroid Surgery.

OBJECTIVES: To determine the prevalence of separate and combined voice and swallowing impairments before and after total thyroidectomy and to delineate risk factors for these symptoms. METHODS: Retrospective review of 592 consecutive patients who underwent total thyroidectomy from July 2003 to August 2015. RESULTS: Combined voice and swallowing problems occurred preoperatively in 4.7% (11/234), 3.3% (3/92), and 6.0% (16/266) of patients with malignancy, hyperthyroidism, and benign euthyroid disease, respectively. Postoperatively, prevalence was 5.1%, 2.2%, and 1.9%, respectively. Benign euthyroid disease (20.7%) had the greatest risk of preoperative dysphagia (P = 0.003) and the largest glands (P < 0.001). Comparing before and after surgery, the cancer and benign euthyroid groups had decreased dysphagia (cancer: 11.5% vs. 6.0%, P = 0.034; benign: 20.7% vs. 3.8%, P < 0.001) but increased dysphonia (cancer: 19.2% vs. 28.6%, P = 0.017; benign: 15.8% vs. 27.1%, P = 0.002). Overall, 23/592 (3.9%) developed new dysphagia and 122/592 (20.6%) developed new dysphonia after surgery. Intraoperative recurrent laryngeal nerve transection occurred in 12 cases (2.0%). CONCLUSIONS: Total thyroidectomy resolved dysphagia but increased dysphonia in benign and malignant euthyroid patients. Voice and swallowing problems following thyroidectomy occurred more frequently than intraoperative recurrent laryngeal nerve transection, confirming symptoms often occur in the absence of suspected nerve injury.

Dysphagia Severity and Outcomes Following Iatrogenic High Vagal Nerve Injury.

OBJECTIVE: To examine severity of dysphagia and outcomes following iatrogenic high vagal nerve injury. METHODS: Retrospective chart review of all patients with iatrogenic high vagal nerve injury that were seen at a tertiary referral center from 2012 to 2020. RESULTS: Of 1304 patients who met criteria for initial screening, 18 met all inclusion criteria. All 18 required intervention to address postoperative dysphagia. Eleven required enteral feeding tubes with 7 eventually able to advance to exclusively per oral diets. Fourteen underwent vocal fold injection and 6 underwent laryngeal framework surgery. Sixteen pursued swallowing therapy with speech language pathology. Patients lost a mean of 8.6 kg of weight in the 6 months following the injury. Swallowing function on the Functional Outcome Swallowing Scale (FOSS) and Functional Oral Intake Scale (FOIS) was 4.4 and 2.4 respectively immediately following the injury and improved to 1.9 and 5.3 at the last follow-up. No patients had complete return of normal swallowing function at last follow up. CONCLUSION: Iatrogenic high vagal injury causes significant lasting dysphagia which improves with intervention but does not completely resolve. Interventions such as vocal fold injection, medialization laryngoplasty, cricopharyngeal myotomy, or swallowing therapy may be required to reestablish safe swallowing in these patients.

Differential Expression of Non-Coding RNA Signatures in Thyroid Cancer between Two Ethnic Groups.

Filipino Americans show higher thyroid cancer recurrence rates compared to European Americans. Although they are likely to die of this malignancy, the molecular mechanism has not yet been determined. Recent studies demonstrated that small non-coding RNAs could be utilized to assess thyroid cancer prognosis in tumor models. The goal of this study is to determine whether microRNA (miRNA) signatures are differentially expressed in thyroid cancer in two different ethnic groups. We also determined whether these miRNA signatures are related to cancer staging. This is a retrospective study of archival samples from patients with thyroid cancer (both sexes) in the pathology division from the last ten years at Loma Linda University School of Medicine, California. Deidentified patient demographics were extracted from the patient chart. Discarded formalin-fixed paraffin-embedded tissues were collected post-surgeries. We determined the differential expressions of microRNA in archival samples from Filipino Americans compared to European Americans using the state-of-the-art technique, HiSeq4000. By ingenuity pathway analysis, we determined miRNA targets and the pathways that those targets are involved in. We validated their expressions by real-time quantitative PCR and correlated them with the clinicopathological status in a larger cohort of miRNA samples from both ethnicities. We identified the differentially upregulated/downregulated miRNA clusters in Filipino Americans compared to European Americans. Some of these miRNA clusters are known to target genes that are linked to cancer invasion and metastasis. In univariate analysis, ethnicity and tumor staging were significant factors predicting miR-4633-5p upregulation. When including these factors in a multivariate logistic regression model, ethnicity and tumor staging remained significant independent predictors of miRNA upregulation, whereas the interaction of ethnicity and tumor staging was not significant. In contrast, ethnicity remained an independent predictor of significantly downregulated miR-491-5p and let-7 family. We provide evidence that Filipino Americans showed differentially expressed tumor-tissue-derived microRNA clusters. The functional implications of these miRNAs are under investigation.

Differential expression of Vitamin D binding protein in thyroid cancer health disparities.

Thyroid cancer incidence, recurrence, and death rates are higher among Filipino Americans than European Americans. We propose that vitamin D binding protein (DBP) with multifunctionality with ethnic variability plays a key role within different ethnicities. In this study, we determined the correlation between differential DBP expression in tumor tissues and cancer staging in Filipino Americans versus European Americans. We assayed DBP expression by immunohistochemistry and analyzed the data with confocal microscopy on 200 thyroid cancer archival tissue samples obtained from both ethnicities. DBP-stable knockdown/gain-in-function assays were done by using DBP-shRNA/DBP-cDNA-expression in vitro. The majority of Filipino Americans presented with advanced tumor staging. In contrast, European Americans showed early staging and very few advanced tumors. A significantly low to no DBP staining was detected and correlated to the advanced staging in Filipino Americans. On the contrary, in the tumor tissues derived from European Americans, moderate to strong DBP staining was detected and correlated to early staging. When downregulation of the DBP gene in papillary thyroid cancer (PTC) cell lines was observed, tumor proliferation and migration were enhanced. On the other hand, the upregulation of the DBP gene decreased cell proliferation and migration in PTC cells. In conclusion, we determined a differential expression of an essential biological molecule (DBP) is linked to cancer staging in thyroid cancer health disparities in two ethnicities. Loss-of-DBP/gain-in-DBP-function influenced tumor progression. A future study is underway to determine the DBP regulation and its downstream pathways to elucidate strategies to eliminate the observed thyroid cancer health disparities.

Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy.

Thyroid carcinoma consists a group of phenotypically heterogeneous cancers. Recent advances in biological technologies have been advancing the delineation of genetic, epigenetic, and non-genetic factors that contribute to the heterogeneities of these cancers. In this review article, we discuss new findings that are greatly improving the understanding of thyroid cancer biology and facilitating the identification of novel targets for therapeutic intervention. We review the phenotypic features of different subtypes of thyroid cancers and their underlying biology. We discuss recent discoveries in thyroid cancer heterogeneities and the critical mechanisms contributing to the heterogeneity with emphases on genetic and epigenetic factors, cancer stemness traits, and tumor microenvironments. We also discuss the potential relevance of the intratumor heterogeneity in understanding therapeutic resistance and how new findings in tumor biology can facilitate designing novel targeting therapies for thyroid cancer.

Cost effectiveness of intraoperative pathology in the management of indeterminate thyroid nodules

ABSTRACT Objective This study aims to determine the cost effectiveness of rapid frozen section (RFS) for indeterminate thyroid nodules. Materials and methods A retrospective chart review was conducted between January 2009 and June 2013 at a tertiary care institution. Main outcomes were number needed to treat, RFS efficacy, and cost-savings of avoiding second completion thyroidectomy. Cost-effectiveness was estimated using 2015 Medicare reimbursement rate. Results Out of 1,114 patients undergoing thyroid surgery, 314 had preoperative AUS/FLUS cytopathology and subsequent thyroid lobectomy with RFS. RFS identified 13 of the 32 patients with malignancy resulting in a total thyroidectomy. 19 of the 29 malignancies not detected by RFS were papillary microcarcinomas. Conclusions Completion thyroidectomy was avoided in 1 out of every 24 patients resulting in cost-savings of $ 80.04 per patient. In the era of outpatient thyroid surgery, intraoperative RFS for indeterminate thyroid nodules is cost-effective.

Cost effectiveness of intraoperative pathology in the management of indeterminate thyroid nodules.

Objective This study aims to determine the cost effectiveness of rapid frozen section (RFS) for indeterminate thyroid nodules. Materials and methods A retrospective chart review was conducted between January 2009 and June 2013 at a tertiary care institution. Main outcomes were number needed to treat, RFS efficacy, and cost-savings of avoiding second completion thyroidectomy. Cost-effectiveness was estimated using 2015 Medicare reimbursement rate. Results Out of 1,114 patients undergoing thyroid surgery, 314 had preoperative AUS/FLUS cytopathology and subsequent thyroid lobectomy with RFS. RFS identified 13 of the 32 patients with malignancy resulting in a total thyroidectomy. 19 of the 29 malignancies not detected by RFS were papillary microcarcinomas. Conclusions Completion thyroidectomy was avoided in 1 out of every 24 patients resulting in cost-savings of $ 80.04 per patient. In the era of outpatient thyroid surgery, intraoperative RFS for indeterminate thyroid nodules is cost-effective.

Total thyroidectomy: Safe and curative treatment option for hyperthyroidism.

BACKGROUND: While use of total thyroidectomy has increased in management of hyperthyroidism, concerns exist about increased surgical complication rates; most notably, hematoma, recurrent laryngeal nerve (RLN) injury, and hypocalcemia. METHODS: Retrospective cohort study of 454 patients undergoing total thyroidectomy between 2003 and 2015. All patients had surgery for hyperthyroidism, benign euthyroid disease, or thyroid malignancy. RESULTS: Total thyroidectomy for hyperthyroidism was not associated with an increased risk for any postoperative complication. Transient hypocalcemia, temporary dysphonia, and postoperative hematoma rates were not significantly different for patients with hyperthyroid (n = 91), euthyroid benign (n = 237), and malignant (n = 126) disease. Permanent hypocalcemia and recurrent laryngeal nerve injury were not noted in any hyperthyroid patients. Complication rates were similar for hyperthyroid patients with Graves' disease vs toxic multinodular goiter. CONCLUSION: This study affirms safety and efficacy of total thyroidectomy as standard treatment for hyperthyroidism.

Surgery versus Imaging in Non-Localizing Primary Hyperparathyroidism: A Cost-Effectiveness Model.

OBJECTIVE: To determine whether advanced imaging is cost-effective compared to primary bilateral neck exploration in the management of non-localizing primary hyperparathyroidism. STUDY DESIGN: Cost-effectiveness analysis. METHODS: Cost-effectiveness analysis based on decision tree model and available Medicare financial data using data from 347 consecutive patients having parathyroidectomy for primary hyperparathyroidism with either 1) positive, concordant ultrasound and sestamibi or 2) negative sestamibi and negative ultrasound. RESULTS: Bilateral neck exploration (BNE) costs $9578 and has a success rate of 97.3%. Single photon emission computed tomography (SPECT) + minimally invasive parathyroidectomy (MIP) was modeled to have a total cost of $8197 with a success rate of 98.6%. SPECT/computed tomography (CT) + MIP was modeled to have a total cost of $8271 and a 98.9% success rate. Four-dimensional (4D)-CT + MIP was modeled to cost $8146 with a success rate of 99%. Incremental cost-effectiveness ratios (IECR) (as compared to BNE) were -536.1, -605.5, and -701.6 ($/percent cure rate) for SPECT, SPECT/CT, and 4D-CT respectively. One-way sensitivity analyses demonstrate the change in IECR and cut-off points (IECR = 0) for four major variables. CONCLUSIONS: In patients with non-localizing primary hyperparathyroidism, advanced imaging is associated with cost-savings compared to routine bilateral neck exploration. Increased cost-savings were predicted with increased imaging accuracy and decreased imaging costs. Increasing time for BNE or decreasing time for MIP were associated with increased cost savings. LEVEL OF EVIDENCE: III Laryngoscope, 2020.

A Qualitative Appraisal of Neurotology Fellowship Websites.

OBJECTIVE: To assess the accessibility and breadth of online information regarding neurotology fellowship programs by appraising individual fellowship websites as well as two popular online databases. METHODS: The American Neurotology Society Program Information Page (ANSPIP), the American Medical Association's Fellowship and Residency Electronic Interactive Database (FREIDA), and three online search engines (Google, Yahoo, Bing) were assessed for accessibility to individual fellowship websites. Each program's ANSPIP data sheet and fellowship-specific website were then evaluated for the presence of 18 characteristics of interest to the neurotology fellowship applicant. RESULTS: All three search engines yielded 23 (96%) Accreditation Council for Graduate Medical Education (ACGME)-accredited neurotology fellowship websites. Searching "Neurotology fellowships" in Google, Yahoo, and Bing required exploring up to nine pages of search results to identify all of the ACGME-accredited program-specific websites. Direct links to program websites were found on 12 (55%) and 3 (13%) of the ANSPIP and FREIDA fellowship pages, respectively. Of the 18 characteristics of interest, the ANSPIP data sheet and individual program websites on average delineated 8.0 and 7.8 characteristics, respectively. Ninety-one percent of fellowship websites included program coordinator information, general program description, and breadth of surgical exposure. In contrast, work/life balance, postfellowship placement, and current fellow(s) were least commonly displayed (4%, 9%, 13% respectively). One-hundred percent of ANSPIP data sheets included program coordinator information, number of fellows, and affiliated hospital(s), whereas none of the pages included selection criteria, application requirements, description of location, or work/life balance. CONCLUSION: Although most neurotology fellowship programs have websites or ANSPIP data sheets, many of them lack information that has been previously demonstrated to be valued by applicants. Furthermore, incongruence of information between these sources may lead to confusion, applicant stress, and reflect poorly on fellowship programs. Perhaps a standardized list of ACGME-required data points to be posted on websites would facilitate the application process.

Cancer stem cell self-renewal as a therapeutic target in human oral cancer.

Tumor recurrence following treatment remains a major clinical challenge in oral cavity cancer. Cancer stem cells (CSCs) have been isolated from human oral cancers and been considered as the driving force of tumor recurrence and metastasis. However, it still remains unclear whether targeting CSCs in oral cancer is a clinically relevant strategy to combat cancer recurrence and metastasis. Here, using clinical cancer specimens and patient-derived xenografts, we show that the self-renewal regulator BMI1 is highly expressed in CSCs of oral cavity squamous cell carcinoma. Inhibition of BMI1 decreases oral CSCs' self-renewal and tumor-initiating potential. Treatment of pre-established human oral cancer xenografts with a BMI1 inhibitor resulted in abrogation of tumor progression and reduced the frequency of CSCs in the xenografts. Remarkably, the BMI1 inhibitor has therapeutic effects in cisplatin-resistant tumors and can reduce metastases initiated by circulating CSCs. Mechanistically, BMI1-inhibition leads to oral CSC necroptotic cell death, which underlies the self-renewal impairment after inhibiting BMI1. Our data provide a pre-clinical proof-of-concept that targeting BMI1-related CSC self-renewal is a clinically relevant anti-cancer therapy in human oral cavity squamous cell carcinoma.

A Randomized Single-Blinded Trial of Ibuprofen- versus Opioid-Based Primary Analgesic Therapy in Outpatient Otolaryngology Surgery.

OBJECTIVE: To compare the efficacy of pain control and opioid consumption between patients who receive opioid as primary analgesic therapy and those who receive ibuprofen. STUDY DESIGN: Prospective randomized trial. SETTING: Tertiary care academic hospital. SUBJECT AND METHODS: Adult patients undergoing outpatient otolaryngology surgery were assigned to take hydrocodone/acetaminophen or ibuprofen for postoperative analgesia. Patient-recorded pain scores and analgesic consumption were analyzed. RESULTS: Out of 185 recruits, 108 (58%) completed responses. Fifty-six patients (52%) received opioid medication for primary analgesic treatment versus 52 (48%) who received ibuprofen. There was no difference in reported pain scores between the treatment groups. Those who received ibuprofen as primary therapy reported a significantly lower consumption of opioid medication at 2.04 tablets/pills (95% CI, 0.9-3.1) versus 4.86 (3.6-6.1; P = .001). Based on multivariate analysis, male sex and older age exhibited lower reported pain scores, while older age and use of ibuprofen as primary therapy exhibited lower opioid requirements. CONCLUSION: For postoperative pain management in outpatient otolaryngology procedures, ibuprofen as primary therapy can provide equally effective pain control as compared with hydrocodone/acetaminophen while decreasing overall opioid requirement. Prescription pill counts are further described to help guide physician practices in the era of an opioid epidemic.

Outcomes of parathyroidectomy for primary hyperparathyroidism with nonlocalizing preoperative imaging.

BACKGROUND: The purpose of this study was to evaluate our surgical experience in patients with primary hyperparathyroidism (PHPT) with nonlocalizing sestimibi and ultrasound scans. METHODS: A retrospective review of 521 patients treated from April 2005 to July 2017 at Loma Linda University Medical Center who received parathyroidectomy for PHPT. One hundred forty-seven patients (28%) had double negative localization (nonlocalizing sestamibi and ultrasound). RESULTS: Surgical cure for PHPT was 97.3% and 99.2% with nonlocalized and localized disease, respectively, and complication rates were similar between groups. Preoperative parathyroid hormone and gland weight were significantly lower with nonlocalization. The incidence of multigland disease (MGD) was greater in patients with nonlocalization on sestamibi and ultrasound. CONCLUSION: Nonlocalization of parathyroid glands was not associated with decreased cure rate or increased morbidity. The presence of MGD and requirement for more extensive surgery were greater in patients with nonlocalizing disease.

Preoperative imaging for parathyroid localization in patients with concurrent thyroid disease: A systematic review.

BACKGROUND: Thyroid disease occurs more frequently in patients with hyperparathyroidism than the general population and hinders parathyroid localization. Identifying thyroid pathology before operating improves management and avoids the risks of reoperation in the neck. This review assesses imaging studies in patients with hyperparathyroidism and thyroid pathology to identify the ideal imaging methodology for patients with multigland disease. METHODS: Systematic review of original articles reporting sensitivity or positive predictive value (PPV) for one or more imaging modalities in patients with hyperparathyroidism and thyroid disease. RESULTS: Twenty-eight studies, 13 prospective and 15 retrospective, met inclusion criteria. Nine modalities were evaluated, including: cervical ultrasound (n = 18), dual-phase 99m Tc-sestamibi (n = 14), subtraction scintigraphy (n = 11), combined ultrasound and scintigraphy (n = 8), single photon emission CT (SPECT; n = 5), SPECT-CT (n = 4), contrast-enhanced ultrasound (n = 1), CT (n = 1), and MRI (n = 1). CONCLUSION: Combined ultrasound and scintigraphy is the most sensitive study to localize parathyroid adenomas in patients with hyperparathyroidism and thyroid disease, followed by hybrid SPECT-CT and SPECT.

Subpopulations of cancer stem cells found in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer and while it has a generally good prognosis, tumor recurrence remains a major clinical challenge. Studying laboratory cell lines as well as clinical specimens indicate that PTC may follow the cancer stem cell (CSC) model. However, CSC characteristics relevant in PTC initiation and progression remain largely unknown. Here we studied a population of sphere-growing tumor cells isolated from primary cultures of clinical PTC. These sphere-growing cells consisted of aldehyde dehydrogenase positive (ALDH+) and ALDH negative (ALDH-) cell subpopulations and demonstrated a hierarchical pattern of cell division. Using combinations of selective depletion, specific inhibition and cell sorting, we found that both subpopulations of the sphere cells were able to self-renew and initiate xenograft tumors independently, and fulfilled the definition of CSC. Importantly, when the subpopulations functioned together, the cancer-initiation efficiency and the xenograft tumor progression were significantly enhanced compared to either subpopulation alone. These data revealed crucial roles of ALDH- CSC in PTC biology and suggested that CSC subpopulations function cooperatively to control PTC initiation and progression. Together, our study indicates that CSC subpopulations isolated from clinical specimens offer unprecedented opportunities for investigating PTC pathogenesis and developing effective therapies.