Utility of Contrast-Enhanced Ultrasound and 4-Dimensional Computed Tomography for Preoperative Detection and Localization of Parathyroid Adenomas Compared With Surgical Results.

OBJECTIVES: To investigate the accuracy, sensitivity, and specificity of contrast-enhanced ultrasound (CEUS) for detection of parathyroid adenomas and compare it to those of 4-dimensional computed tomography (4DCT), which has been established as a reliable, effective tool for preoperative localization of parathyroid adenomas. METHODS: About 27 patients with suspected parathyroid pathology underwent imaging evaluations with 4DCT and CEUS and 22 patients subsequently underwent surgical resection of parathyroid lesions. 4DCT and CEUS were performed and interpreted by consensus of two expert radiologists with extensive experience in each modality. Assessment for the side, z-axis (craniocaudal axis), and quadrant of the pathologically proven lesion was performed based on the surgical report. RESULTS: For single-gland disease, the accuracy for CEUS localization to the correct quadrant and side were 81.0 and 90.1% respectively. For single-gland disease, the accuracy for 4DCT localization to the correct quadrant and side were 81.0 and 90.5% respectively. 4DCT localization sensitivity and specificity were comparable to those for CEUS. 4DCT allowed for accurate diagnosis in multigland disease in contradistinction to CEUS. CONCLUSIONS: CEUS is a noninvasive, real-time imaging technique that has relatively high diagnostic confidence and accuracy of localization which are comparable to the accuracy of 4DCT for preoperative parathyroid adenoma detection, characterization, and localization. This technique should be considered for primary preoperative diagnosis, especially in younger patients.

A germline mutation of HRPT2/CDC73 (70 G>T) in an adolescent female with parathyroid carcinoma: first case report and a review of the literature.

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism amongst children, with only nine previously reported cases. The objective of the study was to present the first pediatric case with a germline CDC73 (formerly known as HRPT2) mutation, and to review the literature. A 14-year-old girl presented with pathologic slipped capital femoral epiphysis (SCFE). The patient was noted to have an elevated calcium level of 3.4 mmol/L (13.4 mg/dL), a parathyroid hormone (PTH) level of 1013 ng/L (1013 pg/mL), and a 3-cm palpable neck mass. Ultrasound and 99mTc-Sestamibi confirmed the suspicion of a parathyroid mass. Intraoperative findings and pathology confirmed the diagnosis of parathyroid carcinoma. Post-operative PTH decreased to 14 ng/L (14 pg/mL). Genetic testing showed a germline 70 G>T HRPT2/CDC73 mutation. This is the first case documenting a germline 70 G>T HRPT2/CDC73 gene mutation in a pediatric parathyroid carcinoma. Patients with sporadic parathyroid carcinoma may benefit from HRPT2/CDC73 gene mutation screening.

Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent.

BACKGROUND: Establishing the preoperative diagnosis and long-term prognosis of differentiated thyroid cancer (DTC) remain challenging in some patients. Myeloid-derived suppressor cells (MDSC) are tumor-induced cells mediating immune tolerance that are detectable in the peripheral blood of cancer patients. The authors previously developed a novel clinical assay to detect the phenotypes of two human MDSC subsets in peripheral blood, and hypothesize that higher MDSC levels measured by this assay correlate positively with both malignancy and worse patient outcomes. METHODS: A prospective observational pilot study was performed of patients undergoing thyroidectomy for a solitary thyroid nodule. The presence of a thyroid nodule >1 cm was confirmed sonographically, and fine-needle aspiration biopsy performed prior to surgery in all cases. Peripheral blood collected preoperatively was analyzed using a novel flow cytometry-based immunoassay to detect and quantify two subsets of human MDSC. Circulating MDSC levels were compared by histopathologic diagnosis, stage, and presence of persistent disease after treatment. RESULTS: Of 50 patients included in this study, MDSC measurement was successful in 47 (94%). One patient was found to have a concurrent cancer, leaving 46 patients for primary analysis. The cytologic diagnoses were benign in five (10.8%), atypia or follicular lesion of undetermined significance in five (10.8%), suspicious for follicular neoplasm in five (10.8%), suspicious for malignant in three (6.5%), and malignant in 28 (60.1%) of the 46 nodules. Final histopathology was benign in 11 (24%) and DTC in 35 (76%), encompassing 34 PTC cases and one follicular thyroid carcinoma. Mean percentages of CD11b(+)HLA-DR(low)HIF1a(+) MDSC (CD11b(+)MDSC) were 14.0 ± 6.2% and 7.9 ± 3.6% in DTC versus benign nodules, respectively (p < 0.005). A cutoff of 12% yielded a specificity of 0.91, a sensitivity of 0.72, and a likelihood ratio of 7.9. Mean CD11b(+)MDSC levels increased linearly with higher TNM stage (p < 0.01), and were 19.4 ± 5.4 in patients with persistent cancer after surgery compared with 13.2 ± 6.8 in those without evidence of disease (p < 0.05). CONCLUSION: MDSC measurement using this flow cytometry-based assay represents a novel approach for preoperatively assessing malignancy risk and cancer extent in patients with thyroid nodules. While further validation is needed, these data suggest that MDSC assessment may serve as a useful adjunct when cytology is indeterminate, and predict tumor stage and recurrence risk in cases of thyroid cancer.

Use of Octreotide for the Management of Chyle Fistula Following Neck Dissection.

IMPORTANCE: Chyle fistula is an uncommon complication of neck surgery. A variety of management strategies have been described, including diet restriction, parenteral nutrition, use of pressure dressings, and revision surgery. Octreotide has been used with success in patients with neck and thoracic chyle fistulas, but data regarding efficacy in neck chyle fistulas are lacking. OBJECTIVE: To evaluate the efficacy of octreotide for use in patients with postoperative chyle fistulas. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 12 patients who received octreotide for neck chylous fistula after neck dissection was performed during the period 2004 through 2014 at 2 tertiary care academic hospitals. EXPOSURES: Patients with postoperative neck chyle fistulas were given a restricted diet and subcutaneous octreotide. MAIN OUTCOMES AND MEASURES: The main outcome was fistula closure rate, defined as fistula resolution without surgical intervention. Secondary outcomes of fistula duration (days from detection until resolution), length of hospital stay (surgery to discharge), and treatment complications were also examined. RESULTS: All 12 patients had resolution of their neck chyle fistula with octreotide therapy without need for revision surgery. Mean (SD) hospital stay was 8.7 (4.76) days, with a range of 3 to 18 days. The chyle fistula resolved after a mean (range) 5.5 (2-11) days. Self-resolving nausea was encountered in 1 patient from octreotide use, and 1 patient developed a salivary fistula as a result of the chylous fistula. CONCLUSIONS AND RELEVANCE: In these patients, octreotide was safe and effective in resolving neck chylous fistulas. Octreotide therapy appears superior to traditional conservative measures of diet restriction and pressure dressings when compared with literature rates. A prospective study is needed to confirm results, but octreotide therapy should be considered as first-line conservative management for neck chyle fistulas that occur after neck surgery.

Overexpression of EphB4, EphrinB2, and epidermal growth factor receptor in papillary thyroid carcinoma: A pilot study.

BACKGROUND: The purpose of this study was to examine the differential expression of EphB4, EphrinB2, and epidermal growth factor receptor (EGFR) genes in papillary thyroid carcinoma (PTC) and evaluate their association with lymph node metastasis. METHODS: EphB4, EphrinB2, and EGFR expression in 21 matched tumors and surrounding normal thyroid tissues were evaluated by complementary DNA (cDNA) microarray, Western blot, and immunohistochemistry (IHC). RESULTS: We noted a statistically significant overexpression of EphB4, EphrinB2, and EGFR in tumor versus normal tissue based on cDNA microarray, Western blot, and IHC analysis. EphB4 and EphrinB2 overexpression were significantly associated with the presence of lymph node disease. CONCLUSION: Overexpression of EphB4, EphrinB2, and EGFR are associated with PTC, whereas EphB4 and EphrinB2 overexpression are associated with lymph node metastases. These genes may be potential biomarkers for identification of subclinical lymph node involvement in PTC and potential small-molecule targets for pharmacotherapy research.

US-guided fine-needle aspiration of major salivary gland masses and adjacent lymph nodes: accuracy and impact on clinical decision making.

PURPOSE: To determine whether ultrasonography (US)-guided fine-needle aspiration (FNA) is an effective technique for diagnosing masses in the salivary gland and adjacent lymph nodes. MATERIALS AND METHODS: The institutional review board waived the requirement to obtain informed consent and approved this HIPAA-compliant retrospective study. Radiology records of 50 patients (28 female patients aged 25-85 years [median age, 58 years], 22 male patients aged 11-82 years [median age, 62 years]) who underwent 52 consecutive US-guided FNA procedures from 2004 to 2009 were reviewed. In 46 cases, lesions were sampled for biopsy under real-time US guidance by means of three passes with a 25-gauge needle. In six cases, two subsequent passes were performed with a 22-gauge needle after the first pass showed minimal or no aspirate. Findings from cytopathologic analysis, clinical follow-up, and surgery were evaluated and compared. RESULTS: A diagnostically adequate biopsy specimen was obtained in 48 of the 52 cases (92%). Among the 20 patients who underwent surgical intervention after diagnostic US-guided FNA findings, results of surgical-pathologic analysis helped confirm the cytologic diagnosis in 19 (95%). Twenty of the 50 patients (40%) were spared surgical intervention on the basis of findings from US-guided FNA. US-guided FNA did not result in any intra- or postprocedural complications. CONCLUSION: The diagnostic accuracy of US-guided FNA is similar to that of core needle biopsy, and there were no complications in this study. Information yielded with FNA cytology plays an integral role in clinical decision making in the management of masses in the major salivary glands and adjacent structures.

Split central venous sampling of parathyroid hormone: an adjunct to surgical exploration.

BACKGROUND: Minimally invasive parathyroid surgery mandates preoperative localization of the adenoma for a targeted operative approach. This technique uses split internal jugular vein parathyroid hormone (PTH) samples to determine a gradient that then directs the surgical exploration. METHODS: Blood samples were drawn low in the neck from the jugular veins after the neck was opened. The p values for the difference in PTH between the right and left internal jugular veins were calculated with independent sample t tests. RESULTS: For left-sided adenomas, the left internal jugular vein mean was significantly higher than the right p = .001). For right-sided adenomas, the right internal jugular vein mean was significantly higher than the left (p = .004). In hyperplasia, there was no significant difference (p = .43). CONCLUSIONS: This study demonstrates the usefulness of split PTH internal jugular vein samples in patients in whom preoperative localization failed. Eighty percent of these patients with a gradient were treated with site-directed unilateral exploration.

Ossicular discontinuity and exostoses in Proteus syndrome: a case report.

Proteus syndrome (PS) is a rare hamartomatous disorder characterized by mosaic overgrowth of multiple tissues that manifests early in life and is progressive. The presence of unilateral external auditory canal exostoses in a patient who is not a swimmer or surfer is suggestive of PS. However, hearing loss is not a typical feature. Here, we describe exostoses and ossicular discontinuity with conductive hearing loss in a patient with PS. The treatment consisted of canalplasty and ossicular chain reconstruction. A postoperative reduction was demonstrated in the patient's air-bone gap, from 21 dB to 13 dB for the pure tone average (four frequencies) and from 41 dB to 15 dB in the high-frequency range (6,000 to 8,000 Hz). Causes of ossicular discontinuity are discussed. Routine annual audiometric and otolaryngological evaluation should be considered in all patients with temporal bone involvement of PS.