Marlon A. Guerrero

MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer

Approximately 30% of fine‐needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy.

Trends of Incidence and Survival of Gastrointestinal Neuroendocrine Tumors in the United States: A Seer Analysis

OBJECTIVES: To examine trends in detection and survival of hollow viscus gastrointestinal neuroendocrine tumors (NETs) across time and geographic regions of the U.S. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) database to investigate 19,669 individuals with newly diagnosed gastrointestinal NETs. Trends in incidence were tested using Poisson regression. Cox proportional hazards regression was used to examine survival. RESULTS: Incidence increased over time for NETs of all gastrointestinal sites (all P < 0.001), except appendix. Rates have risen faster for NETs of the small intestine and rectum than stomach and colon. Rectal NETs were detected at a faster pace among blacks than whites (P < 0.001) and slower in the East than other regions (P < 0.001). We observed that appendiceal and rectal NETs carry the best prognosis and survival of small intestinal and colon NETs has improved for both men and women. Colon NETs showed different temporal trends in survival according to geographic region (Pinteraction = 0.028). Improved prognosis was more consistent across the country for small intestinal NETs. CONCLUSIONS: Incidence of gastrointestinal NETs has increased, accompanied by inconsistently improved survival for different anatomic sites among certain groups defined by race and geographic region.

Clinical Spectrum of Pheochromocytoma

BACKGROUND Pheochromocytomas vary in presentation, tumor size, and in catecholamine production. Whether pheochromocytoma size correlates with hormone levels, clinical presentation, and perioperative complications is not known. The goal of this study was to determine if tumor size and hormone level correlate according to the clinical presentation at diagnosis. STUDY DESIGN We retrospectively analyzed all patients who underwent an adrenalectomy with a diagnosis of a pheochromocytoma from February 1996 to October 2008. We grouped patients according to their clinical presentation at diagnosis (routine biochemical screening, incidentaloma, classic symptoms, pheochromocytoma crisis) and obtained preoperative radiographic tumor size and catecholamine hormone levels. ANOVA was used for the group effects and the Kruskal-Wallis rank test was used for pairwise comparison between groups with the Sidak/Bonferroni method for multiplicity adjustment according to age, tumor size, and hormone level. The Pearson correlation coefficient was then calculated to determine if hormone level correlated with tumor size. RESULTS Eighty-one of 107 patients had data available for complete analysis. The average age at diagnosis for all patients was 47.1 years, and the average tumor size was 4.9 cm. The average highest hormone ratio among all patients was 27.4. Tumor size and hormone ratio levels differed among all groups (p < or = 0.03). A direct correlation (p = 0.014) was apparent between tumor size and hormone level. Complication rates also differed among the four groups of patients (p < or = 0.02). CONCLUSIONS Our study showed that tumor size directly correlates with hormone level. Smaller tumors tend to secrete lower levels of catecholamines, but larger tumors have a wider variation in secretory potential. Larger tumors, however, produced the highest hormone ratios.

Distinct loci on chromosome 1q21 and 6q22 predispose to familial nonmedullary thyroid cancer: A SNP array-based linkage analysis of 38 families

BACKGROUND Familial nonmedullary thyroid cancer (FNMTC) is associated with earlier onset and more aggressive behavior than its sporadic counterpart. Although candidate chromosomal loci have been proposed for isolated families with variants of FNMTC, the etiology of most cases is unknown. We aimed to identify loci linked to FNMTC susceptibility using single-nucleotide polymorphism (SNP) array-based linkage analysis in a broad sampling of affected families. METHODS We enrolled and pedigreed 38 FNMTC families. Genomic DNA was extracted from the peripheral blood of 110 relatives, and hybridized to Affymetrix SNP arrays. We performed genotyping and linkage analysis, calculating exponential logarithm-of-the-odds (LOD) scores to identify chromosomal loci with a significant likelihood of linkage. RESULTS Forty-nine affected and 61 unaffected members of FNMTC families were genotyped. In pooled linkage analysis of all families, 2 distinct loci with significant linkage were detected at 6q22 and 1q21 (LOD=3.3 and 3.04, respectively). CONCLUSION We have identified 2 loci on chromosomes 1 and 6 that demonstrate linkage in a broad sampling of FNMTC families. Our findings suggest the presence of germline mutations in heretofore-undiscovered genes at these loci, which may potentially lead to accurate genetic tests. Future studies will consist of technical validation and subset analyses of higher-risk pedigrees.

Risk Factors for Decreased Quality of Life in Thyroid Cancer Survivors: Initial Findings from the North American Thyroid Cancer Survivorship Study

BACKGROUND The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. METHODS Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. RESULTS A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. CONCLUSION Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing.

Diagnostic markers and prognostic factors in thyroid cancer

There has been considerable progress identifying biomarkers in thyroid tumors that improve the accuracy of fine-needle aspiration biopsy and also help predict tumor aggressiveness or behavior. In this review we address both the clinical potential of molecular biomarkers and their usefulness, based on the most recent literature. We describe the current best clinical staging systems and the common somatic mutations in thyroid cancer. The BRAF mutation is the most common mutation in papillary thyroid cancer and has recently been reported to be associated with disease aggressiveness; it is also an independent predictor of tumor behavior. Combined testing of RET/PTC, NTRK, RAS and PAX8-PPARgamma, which are mutually exclusive mutations, helps improve the accuracy of fine-needle aspiration biopsy. Gene-expression profiling studies have identified a variety of potential molecular markers to help distinguish benign from malignant thyroid neoplasms. Expression analysis of differentially expressed microRNAs also appears to be a promising diagnostic approach for distinguishing benign from malignant thyroid neoplasm. It is especially useful for indeterminate nodules by fine-needle aspiration biopsy.

Serum thyroglobulin is a poor diagnostic biomarker of malignancy in follicular and Ḧurthle-cell neoplasms of the thyroid

BACKGROUND Serum thyroglobulin (Tg) is the most accurate biomarker for thyroid cancer recurrence. However, some clinicians measure preoperative Tg as a diagnostic cancer marker despite lack of supporting evidence. We examined whether Tg accurately predicts malignancy in follicular or Hürthle-cell neoplasms. METHODS We reviewed 366 patients who underwent thyroidectomies for follicular/Hürthle-cell neoplasms. We compared Tg in malignant versus benign tumors by univariate and receiver-operator characteristic analyses. We also examined several Tg-derived indices that normalized Tg to known confounding factors including nodule size, thyroid function, and type of Tg assay. RESULTS Thirty-nine patients met inclusion criteria for analysis. There were no differences between malignant (n = 16) and benign (n = 23) lesions in Tg or any of the normalized indexes. Receiver-operator characteristic analysis revealed an area under the curve of .59. Lesions with Tg levels greater than 500 mug/L had a positive predictive value of .75. CONCLUSIONS Tg has poor accuracy for predicting malignancy in follicular or Hürthle-cell thyroid neoplasms.

Comprehensive Literature Review: Recent Advances in Diagnosing and Managing Patients with Poorly Differentiated Thyroid Carcinoma

Poorly differentiated thyroid carcinomas are a rare form of thyroid carcinomas; they display an intermediate behavior between well-differentiated and anaplastic thyroid carcinomas. PDTCs are more aggressive than the well-differentiated, but less aggressive than the undifferentiated or anaplastic, forms. No clinical features can accurately diagnose poorly differentiated thyroid carcinomas. Thus, the results of histocytology, immunohistochemistry, and molecular genetics tests aid in diagnosis. Given the aggressiveness of poorly differentiated thyroid carcinomas and the poor survival rates in patients who undergo surgery alone, a multimodality treatment approach is required. We conducted a comprehensive review of the current diagnostic and therapeutic tools in the management of patients with poorly differentiated thyroid carcinomas.

Bilateral neck exploration in primary hyperparathyroidism--when is it selected and how is it performed?

BackgroundAlthough most patients with primary hyperparathyroidism (PHPT) are ideal candidates for minimally invasive parathyroidectomy, some will have more than one enlarged gland and require bilateral neck exploration to achieve biochemical cure. We evaluated the clinical evidence for when to choose bilateral neck exploration for patients with PHPT.MethodsWe searched PubMed for English-language studies published from 1996 to 2008. The level of clinical evidence was determined according to the criteria proposed by Sackett (Chest 95[2 Suppl]:2S, 1989), and the grade of recommendation was established according to the criteria proposed by Heinrich et al. (Ann Surg 243:154, 2006).ResultsLevel III–IV evidence shows that patients with multiple endocrine neoplasia (MEN) 1 and PHPT should have a bilateral neck exploration (grade C recommendation). Only level IV evidence indicates that patients with familial PHPT should do so (no recommendation). Although most patients with MEN 2A have single-gland disease, bilateral neck exploration is still indicated, because they will have either a therapeutic or prophylactic total thyroidectomy for medullary thyroid cancer. A history of head and neck irradiation is associated with PHPT, but the risk of multi-gland parathyroid disease is apparently no higher than in sporadic cases (level IV evidence, no recommendation). Previous or current lithium therapy confers a higher risk of multi-gland disease (25%–45%; level IV–V evidence), which may require bilateral neck exploration. Preoperative localizing studies reliably identify most patients with single-gland but not multi-gland disease (level II–IV evidence). Negative localizing studies confer an approximately 50% risk of multi-gland disease and indicate that bilateral neck exploration is necessary. If two localizing studies are concordant, few patients will require bilateral neck exploration (level IV, no recommendation).ConclusionsNo level I or II evidence reliably identifies preoperative clinical risk factors for determining which patients should have routine bilateral neck exploration for multi-gland disease or for intraoperative decision making to convert to bilateral neck exploration. Imaging studies are positive in most patients (level II). No randomized studies exist to determine when a bilateral neck exploration is indicated based on clinical risk factors or imaging studies that may suggest multi-gland disease.

Cryopreservation of parathyroid glands.

The risk of permanent hypoparathyroidism following thyroid and parathyroid surgery is around 1% in the hands of experienced endocrine surgeons. Although this complication is rare, rendering a patient permanently aparathyroid has significant consequences on the health and quality of life of the patient. Immediate autotransplantation of parathyroid glands that are injured or unintentionally removed offers the best possibility of graft viability and functionality. However, since the majority of cases of hypoparathyroidism are transient, immediate autotransplantation can complicate postoperative surveillance in certain patients, especially those with primary hyperparathyroidism. Cryopreservation of parathyroid tissue is an alternate technique that was developed to treat patients with permanent hypoparathyroidism. This method allows for parathyroid tissue to be stored and then autotransplanted in a delayed fashion once permanent hypoparathyroidism is confirmed. This article provides a contemporary review on cryopreservation of parathyroid tissue and its current role in thyroid and parathyroid surgery.