Adrienne Melck

Meta-Analysis and Meta-Review of Thyroid Cancer Gene Expression Profiling Studies Identifies Important Diagnostic Biomarkers

PURPOSE An estimated 4% to 7% of the population will develop a clinically significant thyroid nodule during their lifetime. In many cases, preoperative diagnoses by needle biopsy are inconclusive. Thus, there is a clear need for improved diagnostic tests to distinguish malignant from benign thyroid tumors. The recent development of high-throughput molecular analytic techniques should allow the rapid evaluation of new diagnostic markers. However, researchers are faced with an overwhelming number of potential markers from numerous thyroid cancer expression profiling studies. MATERIALS AND METHODS To address this challenge, we have carried out a comprehensive meta-review of thyroid cancer biomarkers from 21 published studies. A gene ranking system that considers the number of comparisons in agreement, total number of samples, average fold-change and direction of change was devised. RESULTS We have observed that genes are consistently reported by multiple studies at a highly significant rate (P < .05). Comparison with a meta-analysis of studies reprocessed from raw data showed strong concordance with our method. CONCLUSION Our approach represents a useful method for identifying consistent gene expression markers when raw data are unavailable. A review of the top 12 candidates revealed well known thyroid cancer markers such as MET, TFF3, SERPINA1, TIMP1, FN1, and TPO as well as relatively novel or uncharacterized genes such as TGFA, QPCT, CRABP1, FCGBP, EPS8 and PROS1. These candidates should help to develop a panel of markers with sufficient sensitivity and specificity for the diagnosis of thyroid tumors in a clinical setting.

The Utility of BRAF Testing in the Management of Papillary Thyroid Cancer

This review summarizes the current literature surrounding BRAF and its significance in thyroid cancer.

Molecular Phenotyping of Thyroid Tumors Identifies a Marker Panel for Differentiated Thyroid Cancer Diagnosis

BackgroundCurrently, a large proportion of individuals undergo thyroidectomy as a diagnostic procedure for cancer. The objective of this work was to evaluate the molecular phenotype of differentiated thyroid cancer (DTC) and benign thyroid lesions to identify molecular markers that allow for accurate thyroid cancer diagnosis.MethodsTissue microarrays consisting of 100 benign and 105 malignant thyroid lesions, plus 24 lymph node samples, were stained for a panel of 57 molecular markers. Significant associations between marker staining and tumor pathology (DTC versus benign) were determined using contingency table and Mann-Whitney U (MU) tests. A Random Forests classifier algorithm was also used to identify useful/important molecular classifiers.ResultsOf the 57 diagnostic markers evaluated 35 (61%) were significantly associated with a DTC diagnosis after multiple testing correction. Of these, in DTC compared with benign thyroid tumors, 8 markers were downregulated and 27 upregulated. The most significant markers for DTC diagnosis were: Galectin-3, Cytokeratin 19, Vascular Endothelial Growth Factor, Androgen Receptor, p16, Aurora-A, and HBME-1. Using the entire molecular marker panel, a Random Forests algorithm was able to classify tumors as DTC or benign with an estimated sensitivity of 87.9%, specificity of 94.0%, and an accuracy of 91.0%.ConclusionEvaluation of the DTC and benign thyroid tumor molecular phenotype has allowed for identification of a marker panel, composed of both established and novel markers, useful for thyroid cancer diagnosis. These results suggest that further study of the molecular profile of thyroid tumors is warranted, and a diagnostic molecular marker panel may potentially improve patient selection for thyroid surgery.

Cell cycle regulators show diagnostic and prognostic utility for differentiated thyroid cancer.

BackgroundDifferentiated thyroid cancer (DTC) generally has a favorable outcome, but some patients develop local recurrence and/or distant metastases and ultimately die of their disease. Molecular markers that accurately predict tumor behavior are lacking. This study’s aim was to ascertain the role of cell cycle regulators in predicting malignant histology and tumor behavior in DTC.MethodsTissue microarrays consisting of 100 benign and 105 malignant thyroid lesions, plus 24 lymph node samples, were stained for p16, p21, p27, p53, p57, p63, cyclin D1, cyclin E, and mdm2. Statistical analysis was used to compare the expression of the markers in benign versus DTC lesions and correlate their expression with clinicopathologic characteristics.Resultsp16, p21, cyclin D1, and cyclin E showed significantly (P < .001) increased expression in DTCs compared with benign thyroid lesions (54.7% vs. 5%, 71.7% vs. 38%, 87.1% vs. 45.7%, and 72.3% vs. 37.4%, respectively). There was no significant difference in expression between benign lesions and DTC for the remaining markers. p16 expression correlated significantly with extrathyroidal tumor extension (P = .02) and the presence of cancer in lymph nodes (P = .03). A total of 73% vs. 45% of the cancers of patients with and without lymph node involvement, respectively, stained positive for p16 (P = .01).ConclusionsThere is a statistically significant difference in the expression of p16, p21, cyclin D1, and cyclin E between DTCs and benign thyroid lesions, and p16 expression correlates with clinicopathologic variables predicting poor outcomes for DTC. These results suggest that evaluation of cell cycle derangement in thyroid tumors may serve as a useful tool for both DTC diagnosis and prognosis.

Harmonic Scalpel Compared to Conventional Hemostasis in Thyroid Surgery: A Meta-Analysis of Randomized Clinical Trials

Background. The studys aim was to determine whether conventional hemostasis (CH) or the Harmonic Scalpel (HS) results in shorter operative times for thyroidectomy and to evaluate the incidence of postoperative complications with each approach. Methods. A literature search was conducted from study inception to September 30, 2008. Included studies randomized thyroidectomy patients to either CH or HS and reported the incidence of postoperative transient recurrent laryngeal nerve dysfunction (RLND) and hypocalcemia. Results. Nine RCTs were included. Use of the HS reduced operative time by 23.1 minutes (95% CI = 13.8, 32.33). There was no difference in the incidence of transient RLND (RR = 1.25, 95% CI = .56, 2.76), but a lower rate of transient hypocalcemia with the use of the HS (RR = .69, 95% CI = .51, .92). Conclusions. The use of HS in thyroidectomy significantly reduces operative time and is associated with a reduction in postoperative hypocalcemia compared to CH.

Pregnancy among residents enrolled in general surgery: a nationwide survey of attitudes and experiences.

BACKGROUND Medical student interest in general surgery has declined, and the lack of adequate accommodation for pregnancy and parenting during residency training may be a deterrent. We explored resident and program director experiences with these issues in general surgery programs across Canada. METHODS Using a web-based tool, residents and program directors from 16 Canadian general surgery programs were surveyed regarding their attitudes toward and experiences with pregnancy during residency. RESULTS One hundred seventy-six of 600 residents and 8 of 16 program directors completed the survey (30% and 50% response rate, respectively). Multiple issues pertaining to pregnancy during surgical residency were reported including the lack of adequate policies for maternity/parenting, the major obstacles to breast-feeding, and the increased workload for fellow resident colleagues. All program directors reported the lack of a program-specific maternity/parenting policy. CONCLUSIONS General surgery programs lack program-specific maternity/parenting policies. Several issues have been highlighted in this study emphasizing the importance of creating and implementing such a policy.

Evaluation of type 1 growth factor receptor family expression in benign and malignant thyroid lesions.

BACKGROUND The aim of this study was to evaluate the diagnostic and prognostic utility of the type 1 growth factor receptor family in the management of differentiated thyroid cancer (DTC). METHODS Tissue microarrays consisting of 100 benign thyroid lesions and 105 malignant thyroid lesions stained for HER1, HER2, HER3, and HER4 were evaluated. RESULTS HER1, HER2, HER3, and HER4 were expressed in 76%, 2%, 57%, and 73% of DTC cases, respectively. HER1 and HER3 showed significantly increased expression, and HER4 showed significantly decreased expression, in DTC compared with benign thyroid lesions. HER3 expression correlated with the presence of lymph node metastasis, tumor type, and higher N stage; the expression of HER4 correlated with lower T stage. A classifier targeting benign versus malignant status with all 4 markers as potential predictors displayed an accuracy, sensitivity, and specificity of 66.8%, 63.5%, and 70.0%, respectively. CONCLUSIONS For DTC, HER1, HER3, and HER4 have diagnostic and prognostic utility, and warrant further study as targets for cancer treatment.

Medication discontinuation after curative surgery for sporadic primary hyperparathyroidism

BACKGROUND Although parathyroidectomy (Ptx) for sporadic primary hyperparathyroidism (PH) improves comorbidities and symptoms, routine Ptx for minimally symptomatic PH remains controversial. Whether successful Ptx translates into discontinuation or dose-reduction of prescribed medications is unknown. METHODS Consecutive patients undergoing curative Ptx for sporadic PH from January 2007 to April 2009 were compared to patients undergoing thyroidectomy (Tx). We reviewed patient demographics, symptoms, comorbid conditions, and pre- and postoperative medications utilizing the Fisher exact test and t test for comparisons. RESULTS Compared to 176 Tx patients, 260 Ptx patients were older (P < .001), more commonly men (P = .006), and had higher preoperative prevalences of every examined PH symptom and comorbid condition. Postoperatively, even minimal PH symptoms improved after Ptx. The mean number of preoperative medications was higher in Ptx patients (4 vs 2.8, P < .001). Discontinuation or dose-reduction of medication occurred in 28 (11%) Ptx patients vs 7 (4%) Tx patients (P = .01). After Ptx, symptom improvement was the predominant reason for beneficial medication changes, and the most common beneficial effect was discontinuation or dose-reduction of chronic analgesics (33%). CONCLUSION PH symptoms are numerous and improve after curative Ptx. Medication use for related symptoms can be beneficially reduced by surgery. Drug profiles should be routinely reviewed and adjusted after parathyroidectomy.

Same-day discharge after unilateral parathyroidectomy is safe.

BACKGROUND Minimally invasive parathyroidectomy (MIP) with intraoperative parathyroid hormone monitoring is the most common surgical approach among endocrine surgeons for primary hyperparathyroidism (PHPT). Overnight hospitalization after MIP represents a drain on resources and may be unnecessary. The aim of this study was to determine the safety of same-day discharge after MIP. METHODS We performed a retrospective cohort study of patients treated for PHPT between August 2010 and July 2015. Patients were stratified by their length of stay in hospital and compared in terms of postoperative complications. RESULTS During the study period 154 MIPs were performed. Of these, 101 patients were discharged on the day of their surgery (group 1) and the remaining 53 stayed 1 or more days (group 2). Three patients in group 2 required readmission within 30 days of discharge (p = 0.039). Seven patients in group 1 and 1 patient in group 2 visited the emergency department within 30 days of discharge (p = 0.72). Two patients in group 1 experienced persistent or recurrent PHPT (p = 0.55). Patients in group 2 were older than those in group 1 (69 v. 61 yr, p < 0.001) and had a higher mean American Society of Anesthesiologists classification of physical status (2.66 v. 2.24, p < 0.001). CONCLUSION Same-day discharge after MIP is a safe practice and saves the cost of an overnight stay in hospital. Same-day discharge should be considered for all patients undergoing MIP if there are no clear indications for overnight hospitalization.

Secondary Hypertension Due To Concomitant Aldosterone-Producing Adenoma and Parathyroid Adenoma

There is a growing body of evidence supporting a bidirectional relationship between parathyroid hormone (PTH) and aldosterone (Aldo). We report a case of secondary hypertension due to concomitant Aldo-producing adenoma (APA) and parathyroid adenoma (PA) requiring both unilateral adrenalectomy and parathyroidectomy.