Toni Beninato

Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical treatment of patients with indeterminate thyroid nodules

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.

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.

Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer

BACKGROUND Altered miRNA expression and down-regulation of Dicer has been shown in various cancers. We investigated Dicer expression and global miRNA environment in correlation with malignant features of thyroid tumors. METHODS Dicer gene expression was assessed for 22 normal thyroids, 16 follicular adenomas, 28 papillary thyroid cancers (PTCs), 10 tall-cell variants of PTC, 11 follicular variants of PTC, as well as the four thyroid cell lines BCPAP, TPC1, KTC1, and TAD2 via quantitative polymerase chain reaction. BRAF((V600E)) mutation screening was completed for 31 neoplasms. Next-generation sequencing was performed on a subset of PTC and normal thyroid. Protein levels were assessed via Western blotting and immunohistochemistry. RESULTS Dicer mRNA was down-regulated in malignant thyroid samples and cell lines compared with normal tissues, benign neoplasms, and the fetal cell line TAD2. Decreased Dicer gene expression in malignant tissues was correlated greatly with aggressive features: extrathyroidal extension, angiolymphatic invasion, multifocality, lymph node and distant metastasis, recurrence, and BRAF((V600E)) mutation. Conversely, increased levels of Dicer protein were observed in malignant tissues and cell lines. Sequencing yielded 19 differentially expressed miRNAs. Eight samples had a nonsignificant a global down-regulation in malignant tissues. CONCLUSION Dysregulation of Dicer and possibly altered expression of miRNAs are associated with aggressive features in thyroid cancers. These findings suggest that disruption in normal miRNA processing involving Dicer may play a role in thyroid cancer progression.

Ten percent tall cells confer the aggressive features of the tall cell variant of papillary thyroid carcinoma

BACKGROUND The tall cell (TC) variant of papillary thyroid carcinoma (PTC) is more aggressive than classic PTC, but the percentage of TC necessary to diagnose this variant has been debated. We aimed to better determine what percentage of TC correlates with a more aggressive phenotype. METHODS Cases from 2005 to 2010 that were the TC variant of PTC or PTC with TC features were identified and compared with classic PTCs. All cases were reviewed to determine what percent, if any, of the tumors consisted of TC. RESULTS One hundred forty-one cases of PTC were reviewed. Eighty-three cases had some TC component, and 58 cases had none. There were no differences in patient demographics. Tumors with ≥10% TC had more extrathyroidal extension, angiolymphatic invasion, positive surgical margin, and lymph node involvement than classic PTC. There were more recurrences in patients with ≥10% TC, but this was not significant. Similar findings were also observed with increasing percentages of TC. CONCLUSION The aggressive features conferred by the presence of TC in PTCs occur with as little as 10% TC and are maintained with increasing percentages. Therefore, TC in a PTC should be reported if they comprise at least 10% of the tumor.

Diagnostic performance of computed tomography for parathyroid adenoma localization; a systematic review and meta-analysis

PURPOSE To perform a systematic review and meta-analysis of the sensitivity and positive predictive value (PPV) of CT for preoperative parathyroid localization in patients with primary hyperparathyroidism (pHPT), and subsequently compare the different protocols and their performance in different patient groups. MATERIALS AND METHODS We performed a search of the Embase, Pubmed and Cochrane Library databases to identify studies published between January 1, 2000 and March 31, 2016 investigating the diagnostic value of CT for parathyroid localization in patients with biochemical diagnosis of pHPT. Performance of CT was expressed in sensitivity and PPV with pooled proportion using a random-effects model. Factors that could have affected the diagnostic performance were investigated by subgroup analysis. RESULTS Thirty-four studies evaluating a total of 2563 patients with non-familial pHPT who underwent CT localization and surgical resection were included. Overall pooled sensitivity of CT for localization of the pathological parathyroid(s) to the correct quadrant was 73% (95% CI: 69-78%), which increased to 81% (95% CI: 75-87%) for lateralization to the correct side. Subgroup analysis based on the number of contrast phases showed that adding a second contrast phase raises sensitivity from 71% (95% CI: 61-80%) to 76% (95% CI: 71-87%), and that adding a third phase resulted in a more modest additional increase in performance with a sensitivity of 80% (95% CI: 74-86%). CONCLUSION CT performs well in localizing pathological glands in patients with pHPT. A protocol with two contrast phases seems to offer a good balance of acceptable performance with limitation of radiation exposure.

Tract Recurrence of a Follicular Thyroid Neoplasm Following Transaxillary Endoscopic Thyroidectomy

BACKGROUND Endoscopic thyroidectomy is gaining popularity, particularly in Asian countries, as an alternative to conventional cervical thyroidectomy. Multiple large case series have been published that confirm the feasibility and safety of this procedure compared to conventional methods. However, no data are available that demonstrate long-term oncologic outcomes or complications. PATIENT FINDINGS A patient who underwent transaxillary gas insufflation thyroidectomy for a follicular neoplasm presented to the authors with a mass along the operative tract 31 months after her first surgery. The mass was found to be a recurrence of the thyroid neoplasm. SUMMARY Since this is a relatively new procedure, the potential complications differ from those of conventional cervical thyroidectomy. Further studies are needed to determine size limitations on nodules considered for endoscopic resection. CONCLUSION When performing these procedures, care should be taken to ensure that the specimen is removed entirely and in one piece. Long-term outcomes data for endoscopic thyroidectomy are warranted prior to this becoming an acceptable standard of care for thyroid surgery.

Application of the new American Thyroid Association guidelines leads to a substantial rate of completion total thyroidectomy to enable adjuvant radioactive iodine

Background. The recently published 2015 American Thyroid Association guidelines recognize lobectomy as a viable alternative for low‐risk cancers and advise more conservative use of radioactive iodine. Some factors indicating adjuvant treatment with radioactive iodine (and therefore completion total thyroidectomy), however, only can be found upon pathologic investigation. Methods. We performed a retrospective analysis including patients with American Thyroid Association low‐ and low‐to‐intermediate risk well‐differentiated thyroid cancer 1–4 cm. We evaluated how often radioactive iodine would be indicated and compared this with our historic rate. A subanalysis was performed to determine the rate of completion total thyroidectomy necessary, based on the indications for adjuvant radioactive iodine therapy. Results. A total of 394/1,000 (39.4%) patients were included for final analysis. Adjuvant radioactive iodine would have been favored in 101/394 (25.6%) of patients, which is 2.5 times less than was given in our historic cohort. Completion total thyroidectomy to enable adjuvant radioactive iodine would have been recommended in 29/149 (19.5%) patients preoperatively eligible for lobectomy. Conclusion. Despite the tightened regulations for radioactive iodine, about 20% of patients with apparently “low‐risk” well‐differentiated thyroid cancer who are eligible for lobectomy may need completion total thyroidectomy because of pathologic findings for which radioactive iodine use is listed as considered or favored by the current guidelines.

Features Associated With Metastases Among Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the Appendix: The Significance of Small Vessel Invasion in Addition to Size.

BACKGROUND: The risk of metastatic disease among carcinoid tumors of the appendix increases with tumor size. However, it is unclear if any features other than size are also associated with an increased risk of metastatic disease. OBJECTIVE: The aim of this study was to review the characteristics of appendiceal carcinoid tumors and determine if other histologic features besides size should guide surgical decision making. DESIGN: This study involved a retrospective case series. SETTINGS: This study was conducted at a single tertiary acute care hospital. PATIENTS: Patients diagnosed with an appendiceal carcinoid tumor between 2000 and 2014 were identified. Goblet cell carcinoids, adenocarcinomas with neuroendocrine features, and tumors from other primary locations were excluded. INTERVENTIONS: Simple appendectomy or segmental/total colectomy with lymphadenectomy was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were metastases, recurrence, and overall survival. RESULTS: Seventy-nine patients were included. The overall incidence of metastatic disease was 10%. Patients with metastatic disease were more likely to be male (75% vs 28%, p = 0.008), have small-vessel invasion (43% vs 5%, p = 0.001), and have larger tumors (median 2.0 cm vs 0.5 cm, p < 0.001). Among tumors <2 cm, the incidence of metastases among tumors with small-vessel invasion was 60% compared with 0% among those without small-vessel invasion (p < 0.001). Among tumors ≥2 cm, the incidence of metastases was 50% irrespective of small-vessel invasion. If small-vessel invasion was used as a second indication for performing a right hemicolectomy along with size ≥2 cm, both the sensitivity and negative predictive value would have been 100% compared with 63% and 96% if size was used alone. Patients with metastatic disease had a higher incidence of recurrence (13% vs 0%, p = 0.003), but overall survival was 100% in both groups. LIMITATIONS: Small sample size, retrospective design, and limited long-term follow-up were the limitations of this study. CONCLUSIONS: Carcinoid tumors of the appendix <2 cm with small-vessel invasion have similar metastatic potential as tumors ≥2 cm. Therefore, a recommendation for a right hemicolectomy should be considered for tumors <2 cm with small-vessel invasion. Additional prospective multicenter studies are warranted.

Prostate-Specific Membrane Antigen Is a Potential Antiangiogenic Target in Adrenocortical Carcinoma.

CONTEXT Adrenocortical carcinoma (ACC) is a rare tumor type with a poor prognosis and few therapeutic options. OBJECTIVE Assess prostate-specific membrane antigen (PSMA) expression as a potential novel therapeutic target for ACC. DESIGN Expression of PSMA was evaluated in benign and malignant adrenal tumors and 1 patient with metastatic ACC. SETTING This study took place at a tertiary referral center. PATIENTS Fifty adrenal samples were evaluated, including 16 normal adrenal glands, 16 adrenocortical adenomas, 15 primary ACC, and 3 ACC metastases. MAIN OUTCOME MEASURES Demographics, PSMA expression levels via real-time quantitative polymerase chain reaction and immunohistochemistry and whole-body positron emission tomography-computed tomography standardized uptake values for 1 patient. RESULTS qPCR demonstrated an elevated level of PSMA in ACC relative to all benign tissues (P < .05). Immunohistochemistry localized PSMA expression to the neovasculature of ACC and confirmed overexpression of PSMA in ACC relative to benign tissues both in intensity and percentage of vessels stained (78% of ACC, 0% of normal adrenal, and 3.27% of adenoma-associated neovasculature; P < .001). Those with more than 25% PSMA-positive vessels were 33 times more likely to be malignant than benign (odds ratio, P < .001). Whole-body positron emission tomography-computed tomography imaging showed targeting of anti-PSMA Zr89-J591 to 5/5 of the patients multiple lung masses with an average measurement of 3.49 ± 1.86 cm and a standardized uptake value of 1.4 ± 0.65 relative to blood pool at 0.8 standardized uptake value. CONCLUSIONS PSMA is significantly overexpressed in ACC neovasculature when compared with normal and benign adrenal tumors. PSMA expression can be used to image ACC metastases in vivo and may be considered as a potential diagnostic and therapeutic target in ACC.

Expanding the Indications for Single-incision Laparoscopic Cholecystectomy to All Patients With Biliary Disease: Is it Safe?

Purpose: The safety of single-incision laparoscopic cholecystectomy (SILC) has been proven in well-selected patients. The objective of this study was to determine whether SILC can be offered to all patients with any indication for cholecystectomy. Methods: A total of 173 consecutive SILCs were performed between January 2010 and November 2012 with no exclusion criteria. Demographic data, operative, and postoperative outcomes were prospectively collected and analyzed. Results: Patients with acute cholecystitis and gallstone pancreatitis had longer operative times and a higher conversion to 4-port cholecystectomy than patients with biliary colic. Similar relationships were seen when comparing patients with obesity to nonobese patients. There were no differences in complication rates between the groups. Conclusions: SILC can be safely offered to patients with a wide spectrum of biliary disease with the understanding that this may result in increased operative times and a higher likelihood of conversion to multiport laparoscopy.