Does BRAF V600E mutation predict aggressive features in papillary thyroid cancer? Results from four endocrine surgery centers.

BACKGROUND: Existing evidence is controversial regarding the association between BRAF mutation status and aggressive features of papillary thyroid cancer (PTC). Specifically, no study has incorporated multiple surgical practices performing routine central lymph node dissection (CLND) and thus has patients who are truly evaluable for the presence or absence of central lymph node metastases (CLNMs). METHODS: Consecutive patients who underwent total thyroidectomy and routine CLND at 4 tertiary endocrine surgery centers were retrospectively reviewed. Descriptive and bivariable analyses examined demographic, patient, and tumor-related factors. Multivariable analyses examined the odds of CLNM associated with positive BRAF status. RESULTS: In patients with classical variant PTC, bivariate analysis found no significant associations between BRAF mutation and aggressive clinicopathologic features; multivariate analysis demonstrated that BRAF status was not an independent predictor of CLNM. When all patients with PTC were analyzed, including those with aggressive or follicular subtypes, bivariate analysis showed BRAF mutation to be associated with LNM, advanced American Joint Committee on Cancer (AJCC) stage, and histologic subtype. Multivariable analyses showed BRAF, age, size, and extrathyroidal extension to be associated with CLNM. CONCLUSION: Although BRAF mutation was found to be an independent predictor of central LNM in the overall cohort of patients with PTC, this relationship lost significance when only classical variant PTC was included in the analysis. The usefulness of BRAF in predicting the presence of LNM remains questionable. Prospective studies are needed before BRAF mutation can be considered a reliable factor to guide the treatment of patients with PTC, specifically whether to perform prophylactic CLND.

Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management.

BACKGROUND: Controversy exists regarding the optimal management of incidentally discovered, small pancreatic neuroendocrine tumors (PNETs). Our aim was to review the outcomes of patients who underwent nonoperative and operative management. METHODS: We retrospectively reviewed patients with nonfunctioning PNETs at our institution from January 1, 2000 to June 30, 2011. Patients were included if the tumor was sporadic and <4 cm without radiographic evidence of local invasion or metastases. RESULTS: Nonoperative patients (n = 77, median age, 67 years; range, 31-94) had a median tumor size of 1.0 cm (range, 0.3-3.2). Mean follow-up (F/U) was 45 months (max. 153 months). Median tumor size did not change throughout F/U; there was no disease progression or disease specific mortality. In the operative group (n = 56, median age, 60 years; range, 27-82), median neoplasm size was 1.8 cm (range, 0.5-3.6). Mean F/U was 52 months (max. 138 months). A total of 46% of the operative patients had some type of complication, more than half due to a clinically significant pancreatic leak. No recurrence or disease specific mortality was seen in the operative group, including 5 patients with positive lymph nodes. CONCLUSION: Small nonfunctioning PNETs usually exhibit minimal or no growth over many years. Nonoperative management may be advocated when serial imaging demonstrates minimal or no growth without suspicious features.

General surgery and otolaryngology resident perspectives on obtaining competency in thyroid surgery.

OBJECTIVE: General surgery (GS) and otolaryngology (OTO) do not require a minimum number of thyroidectomies to qualify for board certification. No standardized criteria exist for declaring competence in this procedure. A survey was created to assess GS and OTO resident perspectives on becoming competent in thyroid surgery. DESIGN: A survey was electronically mailed to all GS and OTO residents assessing their competence in thyroid surgery. SETTING: National survey of general surgery and otolaryngology residents. PARTICIPANTS: National general surgery and otolaryngology residents. RESULTS: A convenience sample of 526 residents responded (246/280 = GS/OTO). The mean clinical year of training was 3.3 (3.1/3.5). Most residents (50%/41%) performed between 1 and 10 thyroid operations. Residents believed 13 and 25 (GS/OTO) thyroidectomies were required by their respective Boards. Both groups felt that 30 (27/33) thyroid operations were necessary to obtain competence (p < 0.01). The most important feature was operative volume with graduated responsibility, followed by guidance under an expert mentor. Analysis of residents PGY4 and greater showed no significant differences. CONCLUSIONS: While residents of both specialties generally agree on learning methods, the perception of readiness to perform thyroid surgery after training is variable. A disconnect is present between the number of cases required for Board certification, the number of cases residents believe are required, and the number of cases residents believe it takes to achieve competency.

Apples and oranges: comparison of ACS-NSQIP observed outcomes with premier's quality manager-predicted outcomes.

The National Surgical Quality Improvement Program (NSQIP) is used by the American College of Surgeons to measure and report surgical quality and outcomes. Premier's Quality Manager (QM) generates expected outcomes from patient charts. The authors compared observed NSQIP morbidity and mortality outcomes with those predicted by QM. NSQIP data for 1919 patients were entered into QM. The discriminatory accuracy of the QM model was assessed using the C statistic (1.0 implies perfect discrimination, and 0.5 implies no discrimination). NSQIP and QM both identified 51 deaths (C statistic, 0.91). NSQIP identified 478 postoperative occurrences, whereas QM predicted 714 patients with at least 1 complication; 223 of these were subclassified as patients with at least 1 morbid complication (C statistic, 0.83). QM did not perform as well in predicting the observed NSQIP morbidities. Surgical leaders and hospital administrators must critically evaluate products before adopting programs designed to improve patient outcomes or making decisions regarding physician practice.

Arrhythmogenic right ventricular dysplasia in pregnancy: a case report.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by progressive fibrous or fibrofatty tissue replacement of the right ventricular myocardium. Interspersed adipocytes and fibrous tissue may provide foci for arrhythmias. The clinical spectrum of ARVD may include asymptomatic premature ventricular complexes to ventricular tachycardia and sudden death. There is currently little information about ARVD in pregnancy. CASE: A 29-year-old primigravida, diagnosed with ARVD 1 year prior to pregnancy, underwent a full-term, uncomplicated pregnancy and delivery while maintained on acebutolol and an implanted cardioverter defibrillator. Her infant was born without an apparent cardiac anomaly or heart rate abnormality. CONCLUSION: Successful management of pregnancy complicated by ARVD can be accomplished with an implanted cardioverter defibrillator and an antiarrhythmic agent. Such patients should be managed with close monitoring during pregnancy for signs and symptoms of arrhythmia and preventive obstetric care appropriate to their clinical profile to optimize normal deliveries.

Complete sequence of the mitochondrial genome of Tetrahymena thermophila and comparative methods for identifying highly divergent genes.

The complete sequence of the mitochondrial genome of Tetrahymena thermophila has been determined and compared with the mitochondrial genome of Tetrahymena pyriformis. The sequence similarity clearly indicates homology of the entire T.thermophila and T.pyriformis mitochondrial genomes. The T.thermophila genome is very compact, most of the intergenic regions are short (only three are longer than 63 bp) and comprise only 3.8% of the genome. The nad9 gene is tandemly duplicated in T.thermophila. Long terminal inverted repeats and the nad9 genes are undergoing concerted evolution. There are 55 putative genes: three ribosomal RNA genes, eight transfer RNA genes, 22 proteins with putatively assigned functions and 22 additional open reading frames of unknown function. In order to extend indications of homology beyond amino acid sequence similarity we have examined a number of physico-chemical properties of the mitochondrial proteins, including theoretical pI, molecular weight and particularly the predicted transmembrane spanning regions. This approach has allowed us to identify homologs to ymf58 (nad4L), ymf62 (nad6) and ymf60 (rpl6).