Prospective Evaluation of the Rate and Impact of Hemolysis on Intraoperative Parathyroid Hormone (IOPTH) Assay Results

Background  

Intraoperative parathyroid hormone (IOPTH) is commonly used during minimally invasive parathyroidectomy. Retrospective evidence suggested that hemolysis may artificially lower IOPTH results. Falsely decreased IOPTH measurements could result in either failed parathyroidectomy or unnecessary bilateral neck exploration.     

Phenylacetate inhibits growth and vascular endothelial growth factor secretion in human thyroid carcinoma cells and modulates their differentiated function.

There is increasing evidence that phenylacetate inhibits growth and modulates differentiation in a variety of tumors with effects on gene expression, and protein prenylation and glycosylation at concentrations that have been safely used in humans. We evaluated the antineoplastic effects of phenylacetate in five thyroid cancer cell lines of follicular cell origin in vitro. We found early growth inhibition occurred with phenylacetate treatment at a dose of 2.5-10 mmol/L. The growth inhibition was cytostatic with the thyroid carcinoma cells arrested in the G0-1 cell phase. When evaluating the effect of phenylacetate on the differentiated functions of thyroid carcinoma cells, phenylacetate exposure: 1) decreased the TSH (10 mU/mL) growth response; 2) increased radioactive iodine (125I) uptake in two out of five cell lines; and 3) inhibited thyroglobulin secretion. Phenylacetate also inhibited the secretion of vascular endothelial growth factor (a glycoprotein dependent on glycosylation for efficient cellular excretion) from the thyroid cancer cell lines. Our results support that phenylacetate has an antiproliferative effect in many cell types, but the differentiating effects were not uniform. Importantly, we have identified that phenylacetate inhibits the secretion of vascular endothelial growth factor, which possibly mediates the antiangiogenic effects observed in vivo. Because of the minimal toxicity associated with phenylacetate treatment in humans, at concentrations we show to have a significant antineoplastic effect in thyroid carcinoma cells, phenylacetate could be useful in patients with differentiated thyroid cancer who fail conventional therapy or as an adjuvant to radioactive iodine therapy in patients with aggressive tumors.     

The microRNA expression changes associated with malignancy and SDHB mutation in pheochromocytoma

Currently, the diagnosis of malignant pheochromocytoma can only be made when there is clinical evidence of metastasis or extensive local invasion. Thus, there is a need for new diagnostic marker(s) to identify tumors with malignant potential. The purpose of this study was to identify microRNAs (miRNAs) that are differentially expressed between benign and malignant pheochromocytomas and assess their diagnostic accuracy. Toward this aim, we analyzed miRNA expression in benign and malignant pheochromocytoma tumor samples using whole genome microarray profiling. Microarray analysis identified eight miRNAs that were significantly differentially expressed between benign and malignant pheochromocytomas. We measured a subset of these miRNAs directly by RT-PCR and found that miR-483-5p, miR-183, and miR-101 had significantly higher expression in malignant tumors as compared to their benign counterparts. Area under the receiver operating curve (AUC) analysis indicated that miR-483-5p, miR-101, and miR-183 could be useful diagnostic markers for distinguishing malignant from benign pheochromocytomas. In addition, these miRNAs could be detected in pheochromocytoma patient serum. Overall our data suggest that misexpression of miR-483-5p, miR-101, and miR-183 is associated with malignant pheochromocytoma.     

Association of Type O Blood with Pancreatic Neuroendocrine Tumors in Von Hippel–Lindau Syndrome

Background

ABO blood type antigens are expressed not only on human red blood cells, but also throughout the gastrointestinal tract and in normal pancreatic tissue. Previous studies have identified an association between ABO blood type and various malignancies. We analyzed the association of ABO blood type with pancreatic neuroendocrine tumors (PNETs) in a high-risk cohort of patients with Von Hippel?CLindau (VHL) syndrome.

Methods

A retrospective review was performed of 798 patients with VHL syndrome. Blood type was confirmed for 181 patients. Fisher??s exact test and Mehta??s modification to Fisher??s exact test were used to test for an association between ABO blood type and manifestations of VHL syndrome.

Results

We found a strong trend for association between O blood type and pancreatic disease manifestation in patients with VHL syndrome (P?=?0.047). More importantly, there was a significant association of O blood type with solid pancreatic lesions consistent with PNETs (P?=?0.0084). Patients with solid pancreatic lesions who met criteria for surgical resection at the National Institutes of Health also had a higher rate of O blood type than those who did not require surgery (P?=?0.051).

Conclusions

Our findings suggest an association between O blood type and pancreatic manifestation of disease in patients with VHL syndrome, especially for PNETs. Screening and surveillance approaches for pancreatic lesions in patients with VHL syndrome should also consider patient blood type. The possibility of A, B, H misexpression in PNETs should also be explored to determine whether the serologic association with disease translates into a relationship with tissue pathology.     

Should total thyroidectomy become the preferred procedure for surgical management of Graves' disease?

This study aims to evaluate our institution's experience with thyroidectomy for Graves' disease, with an emphasis on indications and long-term outcomes. The study cohort consisted of 103 patients (mean age 34.3 [+/-13.9] years), who underwent thyroidectomy for Graves' disease between 1991 and 2002. Clinical and follow-up data were obtained by retrospective review of medical records and by contacting treating physicians or patients. The most common surgical indications were patient preference (26%), cold nodule (24%), eye symptoms (20%), large goiter size (18%), allergy to antithyroidal medications (15%), and age younger than 16 years (14%). Thyroidectomies performed included 45 (total or near-total), 57 subtotal, and 1 lobectomy. Transient complications included hypocalcemia in 42 patients, and recurrent laryngeal nerve palsy in 5 patients. There was no difference in the frequency of hypocalcemia in patients undergoing total or subtotal resections. One patient developed permanent hypocalcemia and 2 permanent recurrent laryngeal nerve (RLN) injury. Only 3 patients who underwent subtotal resections remain off thyroxine and 2 developed recurrent hyperthyroidism approximately 17 and 54 months after surgery. Subtotal thyroidectomy is associated with a high rate of hypothyroidism and large remnants have potential for recurrence. Total or near-total thyroidectomy obviates these disadvantages and can be performed without increased complication rates, thus appearing to be the preferred extent of thyroidectomy for Graves' disease.