Thyroid cancer is more likely to be detected incidentally on imaging in private hospital patients.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is increasing. Patients with higher socioeconomic status have higher rates of WDTC, possibly due to increased imaging and overdiagnosis. We compared methods of WDTC diagnosis in patients treated at a public and an adjacent private university hospital. MATERIALS AND METHODS: Patients with WDTC at the two hospitals between 2004 and 2010 were included. Patients were categorized into having their WDTC discovered on physical examination or on unrelated imaging. Demographic and pathologic data were collected. T-test was used for quantitative variables, and chi-squared test was used for categorical values. Binomial logistic regression was used to asses for confounding. RESULTS: Among 473 patients, 402 (85%) were from the university hospital, and 71 (15%) were from the public hospital. Patients from the university hospital were older (mean age: 49 versus 44, P = 0.02) and had a different racial composition compared to those from the public hospital. The patients at the public hospital had larger tumors (23 versus 18 mm, P = 0.04). Patients from the university hospital were more likely to have WDTC detected by imaging than patients in the public hospital (46% versus 28%, P < 0.01) on univariate analysis. CONCLUSIONS: This study demonstrates that patients with WDTC treated at a university hospital are more likely to have their tumor detected on unrelated imaging than those treated at a public hospital. These data may support the hypothesis that patients with improved insurance are more likely to have WDTC detected by imaging.

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

OBJECTIVE: Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. METHODS: This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. RESULTS: From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. CONCLUSION: The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. ABBREVIATIONS: AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radio-active iodine US = ultrasound.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: THE INCREASING INCIDENCE OF THYROID CANCER.

OBJECTIVE: (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action. METHODS: Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013. RESULTS: The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease. CONCLUSION: Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers.

Thyroid carcinoma-associated genetic mutations also occur in thyroid lymphomas.

Molecular testing for mutations activating the mitogen-associated protein kinase signaling pathway is being used to help diagnose thyroid carcinomas. However, the prevalence of these mutations in thyroid lymphomas has not been reported. Therefore, we studied the prevalence of BRAF, NRAS, HRAS, and KRAS mutations in 33 thyroid lymphomas and correlated the mutational status with the clinical, pathological, cytogenetic, and immunophenotypic findings. Eleven cases were also tested for PAX8/PPARγ translocations. The lymphomas included 25 diffuse large B-cell lymphomas, 6 extranodal marginal-zone lymphomas of mucosa-associated lymphoid tissue type, and 2 follicular lymphomas. Seventeen diffuse large B-cell lymphomas were germinal center type, six non-germinal center type, and two unclassifiable (Hans algorithm). None of the cases had an associated thyroid carcinoma. Mutations of the BRAF gene were identified in six (24%) diffuse large B-cell lymphomas (D594G in three germinal center diffuse large B-cell lymphomas, K601N in two germinal center diffuse large B-cell lymphomas, and V600E in one non-germinal center diffuse large B-cell lymphoma) and of the NRAS gene in two (8%) non-germinal center diffuse large B-cell lymphomas (Q61K and Q61H). BRAF and NRAS mutations were not found in any extranodal marginal-zone lymphomas of mucosa-associated lymphoid tissue type or follicular lymphomas. HRAS and KRAS mutations were not identified in any of the cases, nor were PAX8/PPARγ translocations found. Thus, interpretation of finding a BRAF or NRAS mutation in the thyroid, particularly in preoperative thyroid aspirates, must take into account the differential diagnosis of a lymphoma. In addition to the diagnostic importance, our data also demonstrate that alteration in the mitogen-associated protein kinase pathway may have a role in the pathogenesis of some large B-cell lymphomas of the thyroid with potential therapeutic implications.

Stones left unturned: Missed opportunities to diagnose primary hyperparathyroidism in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a sequela of primary hyperparathyroidism and an indication for parathyroidectomy. The prevalence of primary hyperparathyroidism in patients with nephrolithiasis is 3% to 5%; however, recent studies suggest that many hypercalcemic patients with nephrolithiasis never undergo workup for primary hyperparathyroidism. Our goal is to evaluate primary hyperparathyroidism screening rates at a tertiary academic health institution and identify opportunities to increase referral rates in patients presenting with nephrolithiasis. METHODS: We retrospectively reviewed 15,725 patients across an academic health system who presented with nephrolithiasis between 2012 and 2020. Calcium levels measured within 6 months of presentation were identified, and those with hypercalcemia (≥10.3 mg/dL) were reviewed if parathyroid hormone levels were measured. Patients with primary hyperparathyroidism were evaluated to see if they were referred to a specialist for treatment. RESULTS: Of 15,725 patients presenting with nephrolithiasis, 12,420 (79%) had calcium levels measured; 630 patients (4.0%) were hypercalcemic, and 207 (33%) had parathyroid hormone levels measured. Patients were more likely to have parathyroid hormone levels sent if they were older, had higher calcium levels, or presented to an outpatient clinic (P = .028, P = .002, P < .001). We identified 89 patients (0.6%) with primary hyperparathyroidism, of which only 35 (39%) were referred for treatment. CONCLUSION: The proportion of patients presenting with nephrolithiasis ultimately diagnosed with primary hyperparathyroidism was significantly lower than others have reported. Additionally, a substantial number of patients with nephrolithiasis did not have calcium and/or parathyroid hormone levels measured. These missed opportunities for diagnosis are critical as early definitive management of primary hyperparathyroidism can prevent recurrent nephrolithiasis and other primary hyperparathyroidism-related end organ effects.

The adrenal mass: correlation of histopathology with imaging.

BACKGROUND: Computed tomography (CT) and magnetic resonance (MR) imaging can help diagnose benign adrenal adenomas, but prior studies rely on nonoperative follow-up as proof of a lesion's benign nature. We examined adrenalectomy tissues to determine if imaging characteristics correlate with histopathologic findings. METHODS: We retrieved data for 196 consecutive adrenalectomies in 192 patients from 2000 to 2008. Imaging results were considered to signify benign adrenal adenoma if one or more of the following was present: Hounsfield units <10 on unenhanced CT, contrast-enhanced CT quantifying absolute contrast washout of >60% or relative contrast washout of >40%, or MR with chemical-shift imaging demonstrating loss of signal intensity on out-of-phase images. RESULTS: The sensitivity and specificity of preoperative imaging in predicting benign adrenal adenoma were 57 and 94%, respectively. Histopathology confirmed that all 66 adrenal masses with imaging characteristics suggesting benign adenoma were indeed benign lesions and included 61 benign adrenal adenomas and 5 benign nonadenomatous lesions (3 myelolipomas, 1 composite myelolipoma/adenoma, and 1 ganglioliponeuroma). The specificity of imaging in predicting benignity was 100%. Malignant adrenal lesions were diagnosed in 17/130 (13%) masses: 8 metastases, 7 adrenal cortical carcinomas, 1 epithelioid angiosarcoma, and 1 ganglioneuroblastoma. The sensitivity of imaging in identifying malignancy was 100%. No malignancies were diagnosed during postoperative follow-up (mean 6 months, range 0.2-67 months). CONCLUSION: CT or MR characteristics predicted the presence of benign lesions with 100% specificity. Every adrenal malignancy had CT or MR results that were inconsistent with benign adenoma (100% sensitivity). To exclude malignancy, adrenal masses with non-benign imaging characteristics should be resected.

Appearance of absorbable gelatin compressed sponge on early post-thyroidectomy neck sonography: a mimic of locally recurrent or residual thyroid carcinoma.

OBJECTIVE: Absorbable gelatin compressed sponge (Gelfoam; Pfizer Inc, New York, NY), a biodegradable agent prepared from purified porcine skin gelatin, is frequently used for intraoperative hemostasis. Its appearance on sonography may mimic tumor or residual thyroid when placed in the resection bed after thyroidectomy. The purpose of this study was to describe the appearance of Gelfoam on early post-thyroidectomy sonography so that an erroneous diagnosis of locally recurrent or residual tumor can be avoided. METHODS: We reviewed the early postoperative sonographic examinations of 6 patients after thyroidectomy in which Gelfoam was used for hemostasis. Screening cervical sonography was performed to identify possible lateral compartment adenopathy before completion of thyroidectomy or ablation. Sonographic examinations were performed up to 50 days after resection. Surgical reports confirmed the use of Gelfoam in each patient. RESULTS: In all cases, uniform elongated echogenicity was shown within the lobectomy bed. In 1 patient, sonographically guided fine-needle aspiration of lobectomy bed echogenicity yielded scant red blood cells, multinucleated giant cells, and macrophages. Follow-up sonography performed in 1 patient 14 months after thyroidectomy confirmed complete Gelfoam absorption. CONCLUSIONS: Gelfoam may mimic residual or recurrent thyroid carcinoma on early surveillance sonography performed after thyroidectomy. Recognition of its characteristic appearance should prompt a search for an appropriate surgical history and, when placed in the appropriate clinical context, should prevent an errant diagnosis of tumor.

Localization of parathyroid adenomas by sonography and technetium tc 99m sestamibi single-photon emission computed tomography before minimally invasive parathyroidectomy: are both studies really needed?

OBJECTIVE: The purpose of this study was to determine the utility of radiologist-performed sonography as the principal modality for parathyroid localization before minimally invasive parathyroidectomy. METHODS: Both sonography and technetium Tc 99m sestamibi single-photon emission computed tomography (SPECT) are commonly performed during imaging evaluation of patients with primary hyperparathyroidism (HPTH). Sonographic examinations ordered during the study period were performed by 1 author (M.E.T.), and results were immediately reported. Findings of a subsequent Tc 99m sestamibi study were recorded blinded to the sonographic results. The sensitivity and specificity of sonography and Tc 99m sestamibi SPECT were assessed with the use of surgery and pathology reports as a reference standard. The 2007 global Medicare reimbursement rates were used to assess the costs of preoperative localization. RESULTS: Parathyroidectomy was performed in 144 of 172 patients evaluated by both modalities. The sensitivity, specificity, and positive predictive value of sonography for identifying abnormal parathyroid glands were 74%, 96%, and 90%, respectively. Sonography correctly localized a single adenoma or suggested multiglandular disease in 112 of 144 patients (78%). The sensitivity, specificity, and positive predictive value of SPECT were 58%, 96%, and 89%. Technetium 99m sestamibi SPECT correctly predicted an adenoma or multiglandular disease in 88 of 144 patients (61%). Five patients with negative sonographic findings were shown to have uniglandular disease on Tc 99m sestamibi SPECT. Selective use of Tc 99m sestamibi SPECT (ie, when sonographic findings were negative or equivocal) would have decreased the cost of imaging by 53%. CONCLUSIONS: Radiologist-performed sonography may potentially be used as a principal imaging modality for patients with HPTH. Selective use of Tc 99m sestamibi in cases with negative or equivocal sonographic findings can decrease the cost of imaging before parathyroid resection considerably.

Does routine consultation of thyroid fine-needle aspiration cytology change surgical management?

BACKGROUND: Routine secondary cytologic review of thyroid gland fine-needle aspiration (FNA) specimens in patients referred from other institutions has been the recommended practice at some medical centers. We sought to determine the concordance rates between FNA interpretations at referring institutions and our center to determine if they alter surgical management. STUDY DESIGN: All thyroid gland FNAs referred to our center for cytopathologic opinion from June 2000 to August 2004 were reviewed. Patients in whom FNA biopsies were performed for thyroid cancer recurrences or core biopsies and patients in whom only a cytopathologic opinion was requested without a clinical consultation were excluded from the study. FNA results were divided into benign, indeterminate, suspicious, malignant, and nondiagnostic categories. FNA interpretations at our medical center and the referring institutions were compared with final histology results in patients who underwent operations. RESULTS: One hundred forty-seven patients had secondary review of their thyroid gland FNA specimens. The overall concordance was 82%, with the highest concordance rate in the malignant category (95%) and the lowest in the suspicious category (62%, p<0.001). The sensitivity (94% versus 92%), specificity (76% versus 56%), and positive (93% versus 87%) and negative (79% versus 69%) predictive values were all higher on secondary review. Twenty-seven patients were found to have discordant FNA interpretations. As a result of the discordant FNA result, four patients had their surgical management decisions changed. Another four patients had appropriate oncologic thyroid resection as a result of the secondary review. CONCLUSIONS: Our results suggest that routine secondary cytopathologic review of FNA specimens from referring institutions changes surgical management in some patients with thyroid neoplasms. We recommend this practice be widely used at other centers, especially for suspicious results.

Parathyroid imaging: technique and role in the preoperative evaluation of primary hyperparathyroidism.

OBJECTIVE: This article discusses the commonly used techniques for imaging the parathyroid glands and their role in the preoperative evaluation of patients with primary hyperparathyroidism. CONCLUSION: The importance of sonography and sestamibi scintigraphy in the preoperative evaluation of patients with primary hyperthyroidism has increased with the adoption of minimally invasive parathyroidectomy techniques at most medical centers. When the results of these studies are concordant, the cure rates of minimally invasive surgery equal those of traditional bilateral neck exploration.

Robot-assisted complete thymectomy for mediastinal ectopic parathyroid adenomas in primary hyperparathyroidism.

One to two percent of ectopic parathyroid adenomas are found in the lower mediastinum and often these are best accessed via a sternotomy or thoracotomy. Video-assisted thoracoscopic surgery (VATS) is an alternative approach with less surgical trauma, decreased morbidity, shorter hospital stays, and superior cosmetic results. Ten years after the first VATS resection of an ectopic mediastinal parathyroid, a robot-assisted thoracoscopic approach was described. Here we describe a series of five robot assisted complete thymectomies in patients with primary hyperparathyroidism due to mediastinal ectopic parathyroid adenomas. A single surgeon, single institution case series of five consecutive robotic-assisted mediastinal parathyroidectomies was performed between March 2013 and September 2015. The patients' ages ranged from 31 to 65, 80 % were female, and all had primary hyperparathyroidism due to an ectopic parathyroid located in the lower mediastinum. Pre-operative imaging workup included Technetium 99-sestimibi parathyroid scan and CT scan of the chest. An ectopic parathyroid adenoma was successfully removed in all five cases, with intraoperative iOPTH decreasing ~50 % from baseline after 10 minutes. A hypercellular parathyroid was confirmed on pathologic exam in all specimens. Post-operative discharge and follow up calcium levels all returned to normal. There were no intraoperative complications, including no recurrent laryngeal nerve injuries, no postoperative morbidity, and no mortalities. This case series demonstrates that a robot-assisted complete thymectomy for mediastinal parathyroid adenomas causing primary hyperparathyroidism provides excellent visualization of the mediastinum, is effective at reducing PTH and calcium levels, and is safe with no morbidity or mortality.

Current status of fine needle aspiration for thyroid nodules.

When not to perform fine needle aspiration of a thyroid nodule In summary, FNA of thyroid nodules has become one of the most useful, safe, and accurate tools in the diagnosis of thyroid pathology. Thyroid nodules that should be considered for FNA include any firm, palpable, solitary nodule or nodule associated with worrisome clinical features (rapid growth, attachment to adjacent tissues, new hoarseness, or palpable lymphadenopathy). FNA should also be performed on nodules with suspicious ultrasonographic features (microcalcifications, rounded shape, predominantly solid composition); dominant or atypical nodules in multinodular goiter; complex or recurrent cystic nodules; or any nodule associated with palpable or ultrasonographically abnormal cervical lymph nodes. Finally, FNA should be performed on any abnormal-appearing or palpable cervical lymph nodes. The management of thyroid nodules based on FNA findings is summarized in Table 2. It can be argued that in certain circumstances the results of thyroid FNA do not change the surgical management of a thyroid nodule, and thus preoperative FNA may be unnecessary. These cases include solitary nodules in patients who have a strong family history of thyroid cancer, multiple endocrine neoplasia type II, or radiation to the head and neck. These patients when they have thyroid nodules have at least a 40% risk for thyroid cancer and frequent multifocal or bilateral disease and should undergo total thyroidectomy with or without central neck lymph node dissection. Patients who have multinodular goiter and compressive symptoms, patients who have Graves disease and a thyroid nodule, or patients who have large (greater than 4 cm) or symptomatic unilateral thyroid nodules could also be considered for total thyroidectomy or lobectomy as indicated without preoperative FNA. Finally, patients who have a solitary hyperfunctioning nodule on radioiodine scan and a suppressed TSH have an extremely low incidence of malignancy and may be considered for therapeutic thyroid lobectomy or radioiodine ablation as indicated without undergoing FNA biopsy.

Method of Detection of Well-Differentiated Thyroid Cancers in Obese and Non-Obese Patients.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is increasing rapidly. Many authors feel that this increase is due to over-diagnosis and that one of the contributing factors is the increasing use of various imaging studies. The rate of obesity has also been increasing in the United States. It has been suggested that patients with an increased body mass index (BMI kg/m2) have a higher incidence of WDTC than patients with normal BMI. One might hypothesize that thyroid nodules are more difficult to palpate in obese patients and that as more cancers are detected by imaging the apparent rate of increase in WDTC in obese patients would appear to be greater than in non-obese patients. This study was undertaken to evaluate this hypothesis by determining if there is any difference in the way thyroid cancers are initially detected in obese and non-obese patients. METHODS: The medical records of all 519 patients with a postoperative diagnosis of WDTC who underwent thyroidectomy at NYU Langone Medical Center from January 1, 2007 through August 31, 2010 by the three members of NYU Endocrine Surgery Associates were reviewed. Patients were divided into Non-obese (BMI<30 kg/m2) and Obese (BMI≥30 kg/m2) groups. Patients were also divided by the initial method of detection of their tumor into Palpation, Imaging, and Incidental groups. RESULTS: The final study group contained 270 patients, 181(67%) of whom were in the Non-obese Group and 89(33%) were in the Obese Group. In the Non-obese group, 81(45%) of tumors were found by palpation, 72(40%) were found by imaging, and 28(16%) were found incidentally. In the Obese group, 40(45%) were found by palpation, 38(43%) were found by imaging, and 11(12%) were found incidentally. These differences were not statistically significant (p-value 0.769). CONCLUSION: We show that BMI does not play a role in the method of initial detection in patients with WDTC. This suggests that the prevalence of WDTC detected by imaging is not an artifact caused by an increasingly obese population and that any association of WDTC and obesity is not related to the way in which these tumors are detected.

Tissue-engineered colon exhibits function in vivo.

BACKGROUND: Postcolectomy morbidities include important changes in enterohepatic circulation, stool microbiology, and absorption. The surgical substitution of an ileal pouch for the absent colon also has a number of serious complications. We report in vivo colon replacement by tissue-engineered colon (TEC) in lieu of an ileal pouch. METHODS: End-ileostomies were created in 22 male Lewis rats. In 11 animals, side-to-side ileum-TEC anastomosis was performed 1 cm from the stoma. This group was compared with end-ileostomy alone. Serial weights were measured, and animals were harvested sequentially for assessment of histologic signs of pouchitis. Transit times, stool dry and wet weights, and serum and stool colon function markers were collected. RESULTS: Animals survived 41 days. Weight loss was more than 1.5 times greater in the end-ileostomy alone group compared with the ileum-TEC group. Transit times were significantly longer in the ileum-TEC group than the end-ileostomy alone group, with lower stool moisture content and higher total serum bile acids. Animals without TEC had statistically significant hyponatremia, elevated serum urea nitrogen, and lower stool short chain fatty acids (13.5 micromol/kg vs 84.2) with an abnormal distribution. CONCLUSIONS: TEC successfully recapitulates some major physiologic functions of native large intestine in vivo.

Cutting too deep? Assessing the impact of a shorter surgery clerkship on students' clinical skills and knowledge.

BACKGROUND: The aim of this study was to compare the performance of students completing an 8-week versus a 6-week surgery clerkship on an objective structured clinical examination (OSCE) and the National Board of Medical Examiners (NBME) clinical science surgery examination. METHODS: One hundred fifteen students from the 8-week clerkship and 99 from the 6-week clerkship were included. Performance on a summative OSCE was assessed using behaviorally anchored checklists. NBME exams were graded using the NBME's standard scaled scores. Results were compared using 2-tailed, independent-samples, unequal-variance t tests. RESULTS: Mean OSCE scores for the 8-week and 6-week curricula were not statistically different. Mean NBME scores also did not statistically differ. Six-week students performed significantly better in the specific OSCE subdomains of blood pressure, orthostatic blood pressure, rectal exam, and fecal occult blood test. CONCLUSIONS: Overall OSCE and NBME exam performance did not differ between 8-week and 6-week surgery clerkship students.

Thyroid cancers detected by imaging are not necessarily small or early stage.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) in the United States is increasing rapidly. Much of this increase is due to the detection by imaging of small, nonpalpable tumors. The incidence of advanced WDTC is also increasing, suggesting a true increase in the incidence of WDTC. This study was performed to determine how WDTCs of all sizes and stages are initially detected. METHODS: A retrospective chart review of 519 patients who underwent surgery for WDTC from January 1, 2007, through August 31, 2010, was performed. A total of 473 patients suitable for inclusion in this study were divided into three groups based upon the method by which the tumor was initially detected: tumors detected by an imaging study (184 patients-39%), those detected because a mass was felt in the neck (218 patients-46%), and those detected incidentally on pathological study of the surgical specimen (71 patients-15%). Method of detection was correlated with age and sex of the patient, and size, stage, and nodal status of the tumor. RESULTS: Patients in the Palpation group were more likely to be female (79% vs. 67% vs. 74%), younger (46 vs. 51 vs. 52), and to have larger tumors than those in the Imaging or Incidental groups. In the Imaging group, the tumor was detected on thyroid sonogram in 98 (53%), computed tomography in 38 (21%), magnetic resonance imaging in 19 (10%), carotid duplex scan in 14 (8%), and positron-emission tomography or other imaging studies in 15 (8%). Thirty-three percent of tumors <1 cm, 51% 1-2 cm, 29% 2-4 cm, and 38% >4 cm were first detected on an imaging study. Forty-seven percent of Stage III and IV cancers in patients aged ≥45 years and 39% of patients with positive central nodes were in the Imaging group. CONCLUSION: This study demonstrates that while most tumors discovered by imaging were small and early stage, almost half of advanced (Stage III and IV) WDTCs were initially discovered by imaging studies. These findings are consistent with the hypothesis that the frequent use of imaging studies may explain not only the increasing incidence of early WDTC, but more advanced thyroid cancers as well.

Clinical and therapeutic implications of Sprouty2 feedback dysregulation in BRAF V600E-mutation-positive papillary thyroid cancer.

BACKGROUND: The BRAF V600E (BRAF+) mutation activates the mitogen-activated protein kinase (MAPK/ERK) pathway and may confer an aggressive phenotype in papillary thyroid cancer (PTC). Clinically, the behavior of BRAF+ PTC, however, varies from an indolent to an aggressive course. SPRY2 is a negative feedback regulator of the MAPK/ERK pathway. We hypothesize that the level of SPRY2 expression contributes to MAPK/ERK pathway output and accounts for BRAF+ and clinical heterogeneity. METHODS: A tissue microarray with BRAF-positive PTCs (BRAF+ PTCs) was constructed and analyzed for SPRY2 expression and MAPK/ERK output. Data were studied in the context of clinicopathologic factors to develop a risk stratification system predictive of tumor biology. SPRY2 function was studied by silencing SPRY2 in BRAF+ PTC cells. These cells were treated with MAPK/ERK pathway inhibitors and assessed for growth effects. RESULTS: BRAF+ PTCs with an intact MAPK/ERK feedback pathway do not exhibit lymph node metastases. BRAF+ PTCs with dysregulated feedback pathways have nodal metastasis. When SPRY2 is silenced, the BRAF+ PTC cells are significantly more sensitive to MAPK/ERK inhibition. CONCLUSION: PTC behavior likely is dependent on both the driver of the MAPK/ERK pathway and its regulatory feedback. When the feedback pathway is intact, the tumor phenotype seems to be less aggressive. This observation has direct and important clinical implications and may alter our treatment strategies.

Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma.

BACKGROUND: BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). We used a mutation-specific antibody for immunohistochemical (IHC) detection of the BRAF V600E mutation and correlated expression with clinicopathologic features. The study was designed to validate the accuracy and determine the clinical importance of IHC detection of the BRAF V600E mutation in PTC. METHODS: Direct sequencing and IHC for BRAF V600E mutation was performed in 37 consecutive patients with PTCs. IHC was scored on an intensity proportion scale. IHC positive tumors were stratified into intensity categories. The categories were assessed for clinicopathologic variables, including age, extrathyroidal extension, lymphovascular invasion, and lymph node metastases. RESULTS: A total of 25 PTCs were BRAF V600E-positive and 12 were BRAF mutation-negative on IHC. The BRAF V600E mutation-specific antibody had a sensitivity of 89% and specificity of 100% for detecting the mutation. Tumors with high-intensity staining were more likely to have extrathyroidal extension. CONCLUSION: IHC is an accurate method for the detection of the BRAF V600E mutation in PTC, and its ability to quantify the mutation expression may serve as a better predictor of tumor behavior than molecular sequencing. It provides a potentially rapid, easily applicable, and economic alternative to current techniques.

Positional dyspnea and tracheal compression as indications for goiter resection.

HYPOTHESES: Goiter is a surgically reversible cause of positional dyspnea (PD). Substernal tracheal compression (TC) predicts PD relief after thyroidectomy (Tx). DESIGN: Retrospective analysis of a prospective structured management algorithm. SETTING: Endocrine surgery academic center. METHODS: Before Tx, 1081 patients were queried about PD. Those patients with substernal goiter underwent computed tomography, and their degree of TC was estimated as greatest percent reduction of transverse tracheal diameter. For 197 patients with PD, TC, or both, surgical outcomes were examined with a mean follow- up of 12.6 months. After Tx, patients who carried the diagnosis of obstructive sleep apnea were referred for repeat sleep study evaluation. RESULTS: Positional dyspnea was reported by 188 of 1081 patients, and after Tx the PD improved or resolved in 82.4%. In the 151 patients with substernal goiter, TC was present on imaging in 97.2%; the mean (range) TC was 34% (5%-90%). Patients with TC had a high likelihood of PD (93.5%). After substernal goiter resection, PD improved in stepwise association with total resected thyroid gland weight. Improvement in PD was strongly predicted by both gland weight of 100 g or more (P.001) and by TC of 35% or more (P.01). After Tx, 59 of 77 snorers (76.6%) reported improvement in snoring, 77.1% of patients with obstructive sleep apnea reported improved PD, and 2 of 3 retested patients with obstructive sleep apnea demonstrated objective improvement in sleep study apnea-hypopnea index. CONCLUSIONS: Resection of bulky goiter frequently improves PD, which in substernal goiter is highly associated with TC. Either PD or TC of 35% or more prompt Tx. Goiter should be considered when obstructive sleep apnea is diagnosed.

Assessment of medical student clinical reasoning by "lay" vs physician raters: inter-rater reliability using a scoring guide in a multidisciplinary objective structured clinical examination.

BACKGROUND: To determine whether a "lay" rater could assess clinical reasoning, interrater reliability was measured between physician and lay raters of patient notes written by medical students as part of an 8-station objective structured clinical examination. METHODS: Seventy-five notes were rated on core elements of clinical reasoning by physician and lay raters independently, using a scoring guide developed by physician consensus. Twenty-five notes were rerated by a 2nd physician rater as an expert control. Kappa statistics and simple percentage agreement were calculated in 3 areas: evidence for and against each diagnosis and diagnostic workup. RESULTS: Agreement between physician and lay raters for the top diagnosis was as follows: supporting evidence, 89% (κ = .72); evidence against, 89% (κ = .81); and diagnostic workup, 79% (κ = .58). Physician rater agreement was 83% (κ = .59), 92% (κ = .87), and 96% (κ = .87), respectively. CONCLUSIONS: Using a comprehensive scoring guide, interrater reliability for physician and lay raters was comparable with reliability between 2 expert physician raters.