BACKGROUND: Preoperative B-type Raf kinase Val600Glu mutation, or BRAF(V600E), analysis has been proposed as a tool to guide initial surgery for indeterminate thyroid nodules. This study sought to determine if cytologic markers of malignancy are associated with the BRAF(V600E) mutation and if preoperative BRAF(V600E) testing would alter the initial management of patients with indeterminate nodules. METHODS: Patients who underwent surgery for a thyroid nodule between 2003 and 2012 at a tertiary care center were prospectively enrolled. Stored nodule samples were retrospectively genotyped for the BRAF(V600E) mutation. BRAF(V600E) status, demographics, cytologic and histopathologic findings, and choice of initial surgery were examined. RESULTS: A total of 960 patients were enrolled, of which 310 (32%) had an indeterminate nodule. The BRAF(V600E) mutation was identified in 13 patients (4%), 12 of whom had either cytologic atypia or were Bethesda category V. Three percent of Bethesda category III or IV nodules that were malignant harbored the mutation compared with 42% of Bethesda category V malignancies. Nuclear grooves (P ¼ .030), pseudoinclusions (P < .001), and oval nuclei (P ¼ .022) were all more common among BRAF(V600E) mutants. The sensitivities of using BRAF testing alone, cytologic atypia/Bethesda category V classification, or both, were 15%, 73%, and 76%, respectively. Twelve of the 13 BRAF(V600E) mutants had total thyroidectomies initially due to worrisome cytologic features, and therefore the initial management of only one patient would have been altered if BRAF(V600E) testing had been performed preoperatively. CONCLUSIONS: Preoperative mutation screening for BRAF(V600E) does not meaningfully improve risk stratification and is unlikely to alter the initial management of patients with indeterminate nodules.
BACKGROUND Gastroesophageal reflux disease (GERD) affects nearly 25% of adults, however an objective diagnosis is rarely established. We hypothesized that patients’ symptoms and response to acid-reducing therapy are poor predictors of the outcome of 24-hour esophageal pH monitoring. METHODS A review of 24-hour esophageal pH monitoring studies performed at an ambulatory tertiary care center between 2004 and 2011 was performed. Demographics, type of GERD symptoms, and duration and response to acid-reducing medications prior to referral for pH monitoring were collected. DeMeester score, symptom sensitivity index (SSI), and symptom index (SI) were tabulated and compared to the patients’ symptoms and response to medical therapy. RESULTS One hundred patients were included. Of all reported symptoms, only heartburn was more common in patients with positive DeMeester scores, but there were no correlations between any symptoms and SSI or SI scores. Sixty-nine percent of patients with esophageal symptoms had a positive DeMeester score compared to only 29% of patients with extraesophageal symptoms (p<0.01). Esophageal symptoms and endoscopic evidence of GERD significantly increased the likelihood of having a positive DeMeester score, but they had no influence on SSI or SI scores. There was no correlation between response to acid-reducing medications and DeMeester, SSI or SI scores. A total of 536 person-years of acid-reducing medications were prescribed to the study population, of which 151 (28%) were prescribed to patients who had a negative pH study. CONCLUSION Extraesophageal symptoms and response to empiric trials of acid-reducing medications are poor predictors of the presence of GERD and the DeMeester score is more likely to identify GERD in patients who met other empiric diagnostic criteria than either SSI or SI. Early referral for 24-hour esophageal pH monitoring may avoid lengthy periods of unnecessary medical therapy.
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