The Role of Facial Gender Confirmation Surgery in the Treatment of Gender Dysphoria.

The population of transgender patients seeking gender confirmation surgery for gender dysphoria is increasing in the United States. Facial gender confirmation surgery (FGCS) is one of the treatment modalities patients require and is often a combination of soft tissue and cranio-maxilla-facial procedures. Despite evidence of the efficacy of FGCS, there remains some extant controversies to address, such as reimbursement for these procedures, categorization of aesthetic versus functional surgery, and evaluation of outcomes. This review provides a discussion of these topics, as well as the historical and psychosocial issues specific to transgender patients that surgeons should know when providing FGCS. We provide practice pearls for providing affirming transgender healthcare, illustrative patient clinical vignettes, and a discussion of the Standards of Care of the World Professional Association for Transgender Health to help guide surgeons who are interested in providing FGCS to transgender patients.

One-Hour Postoperative Parathyroid Hormone Levels Do Not Reliably Predict Hypocalcemia After Thyroidectomy.

INTRODUCTION: Hypocalcemia is a well-known complication after total thyroidectomy. Studies have indicated that the presence of low postoperative parathyroid hormone (PTH) levels can predict hypocalcemia. However, definitive study designs are lacking. The aim of this study was to determine whether postoperative PTH alone can accurately predict postoperative biochemical hypocalcemia. METHODS: Under IRB approval, a prospective study of 218 consecutive patients who underwent total or completion thyroidectomy by two surgeons between June 2014 and June 2016 was performed. Biochemical hypocalcemia was defined as ionized calcium <1.13 mmol/L or serum calcium <8.4 mg/dL at any time postoperatively. Three PTH thresholds, <10, <20 pg/mL, and >50% drop in PTH 1 h postoperatively from baseline were examined. RESULTS: Postoperative PTH < 10 pg/mL had a sensitivity of 36.5% (95% CI 27.4-46.3%) and a specificity of 89.2% (95% CI 81.9-94.3%). Postoperative PTH < 20 pg/mL had a sensitivity of 66.4% (95% CI 56.6-75.2%) and a specificity of 67.6% (95% CI 58.0-76.2%). Postoperative PTH decrease >50% had a sensitivity of 63.4% (95% CI 53.2-72.7%) and a specificity of 72.5% (95% CI 62.5-81.0%). Across all PTH thresholds, the false-negative rate was 33.6-63.5% indicating that up to 64% of patients with a normal PTH level could have been discharged without appropriate calcium supplementation. The false-positive rate was 10.8-32.4% indicating that up to 32.4% of patients with low PTH could have been treated with calcium supplementation unnecessarily. CONCLUSION: Following total thyroidectomy, PTH levels are unreliable in predicting hypocalcemia. Additional prospective studies are needed to understand the true utility of PTH levels post-thyroidectomy.

Gastric and small intestine gastrointestinal stromal tumors: Do outcomes differ?

BACKGROUND AND OBJECTIVES: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Previous literature has suggested that small intestine GISTs are more aggressive than gastric GISTs. Our primary objective was to compare the outcomes of gastric and small intestine GISTs in the decade after approval of imatinib for treatment. METHODS: The SEER database was queried for cases of gastric and small intestine GIST between the years 2002 and 2012, using the ICD-O-3 histology code 8936. Survival analysis was performed using generalized gamma models for time to cause-specific mortality (CSM). RESULTS: CSM was 14.0% for the 3,759 gastric GIST patients and 14.3% for the 1,848 small intestine GIST patients. Five-year survival was 82.2% and 83.3% for gastric and small intestine patients, respectively. The number of diagnosed cases of GIST increased over the course of this study, especially for tumors <5 cm in size and in patients over age 50 years. CONCLUSIONS: In this large nation-wide study, we found that patients with gastric and small intestine GISTs had similar outcomes, in contrast to previous reports. The diagnosis of GIST has significantly increased in the last decade, which may reflect the increased recognition of this entity and frequent use of imaging. J. Surg. Oncol. 2017;115:351-357. © 2016 Wiley Periodicals, Inc.

Below-knee endovascular interventions have better outcomes compared to open bypass for patients with critical limb ischemia.

Both open surgery and endovascular peripheral interventions have been shown to effectively improve outcomes in patients with peripheral artery disease, but minimal data exist comparing outcomes performed at and below the knee. The purpose of this study was to compare outcomes following infrageniculate lower extremity open bypass (LEB) versus peripheral vascular intervention (PVI) in patients with critical limb ischemia. Using data from the 2008-2014 Vascular Quality Initiative, 1-year primary patency, major amputation, and mortality were compared among all patients undergoing LEB versus PVI at or below the knee for rest pain or tissue loss. Overall, 2566 patients were included (LEB=500, PVI=2066). One-year primary patency was significantly worse following LEB (73% vs 81%; p<0.001). One-year major amputation (14% vs 12%; p=0.18) and mortality (4% vs 6%; p=0.15) were similar regardless of revascularization approach. Multivariable analysis adjusting for baseline differences between groups confirmed inferior primary patency following LEB versus PVI (HR 0.74; 95% CI, 0.60-0.90; p=0.004), but no significant differences in 1-year major amputation (HR 1.06; 95% CI, 0.80-1.40; p=0.67) or mortality (HR 0.71; 95% CI, 0.44-1.14; p=0.16). Based on these data, we conclude that endovascular revascularization is a viable treatment approach for critical limb ischemia resulting from infrageniculate arterial occlusive disease.

Intraoperative PTH May Not Be Necessary in the Management of Primary Hyperparathyroidism Even with Only One Positive or Only Indeterminate Preoperative Localization Studies.

BACKGROUND: Intraoperative PTH (IOPTH) monitoring has been widely used to confirm the removal of the culprit lesion during operation. However, the true benefit of IOPTH in patients with preoperatively well-localized single adenoma has been questioned. The aim of this study was to examine how or if IOPTH changes the surgical management and outcomes in patients with only one positive or only indeterminate localization studies. METHODS: This is a retrospective review of data from a parathyroid surgery database and patient records from July 2004 to June 2014, including patients with primary hyperparathyroidism with a planned MIP by two experienced endocrine surgeons after ≥1 positive/indeterminate preoperative localization study by ultrasound and/or sestamibi. RESULTS: A total of 482 patients with positive (342: 259 only 1, 83 with ≥2) or indeterminate (140: 105 only 1, 35 with ≥2) preoperative imaging studies were included. IOPTH changed the management in only 16 (3%) patients, with an additional lesion found in 12 of them. Surgical cure was achieved in 471 (98%) of patients (98% in the positive vs. 97% in the indeterminate group, p 0.58). With or without IOPTH, the cure rate would not have been significantly different in patients with only 1 positive preoperative imaging (96 vs. 98%, p 0.12). Similar results were seen in those with ≥2 indeterminate (100% cure rate with or without IOPTH). CONCLUSION: Our study suggests that MIP may be safely and successfully performed without IOPTH for patients with ≥1 positive or ≥2 indeterminate preoperative imaging studies. This study is retrospective within inherent biases, and future prospective study is warranted.

Validation of a modified Frailty Index to predict mortality in vascular surgery patients.

BACKGROUND: Patient frailty has been implicated as a predictor of poor patient outcomes; however, there is no consensus on how to define or quantify frailty to assess perioperative risk. A previously described modified Frailty Index (mFI) has been shown to predict adverse outcomes after selected vascular surgical procedures, but no studies to date have compared its utility against other recognized risk indices in specific populations of vascular surgery patients. METHODS: National Surgical Quality Improvement Program data were reviewed for all patients undergoing carotid revascularization, abdominal aortic aneurysm (AAA) repair, and lower extremity revascularization for peripheral arterial disease (PAD) from 2006 to 2012. Patients were then further stratified into "open" and "endovascular" cohorts. The mFI was compared with the Lee Cardiac Risk Index (LCRI) and the American Society of Anesthesiologists (ASA) Physical Status Classification using a receiver operating characteristic area under curve (AUC). The primary end point was 30-day mortality, with a secondary end point of Clavien-Dindo class IV complications. RESULTS: A total of 72,106 patients were identified in the study period, with 40,931 (56.8%), 20,975 (29.1%), and 10,200 (14.1%) in the carotid, AAA, and PAD populations, respectively. For carotid endarterectomy, mFI demonstrated better discrimination regarding mortality than LCRI and ASA, with an AUC of 0.66 (95% confidence interval [CI], 0.63-0.70; P < .01 vs P = .65 and P = .60, respectively). The open AAA cohort had similar findings, with an AUC of 0.63 (95% CI, 0.59-0.67; P = .02 vs P = .58, and P = .58, respectively). In open PAD patients, mFI was comparable to ASA (AUC, 0.64 [95% CI 0.60-0.69] vs 0.65), with a trend toward better discrimination compared with the 0.60 AUC of LCRI (P = .08). The mFI was a better discriminator of class IV complications than LCRI and ASA after open AAA (AUC for mFI, 0.59 vs 0.56 and 0.55; 95% CI, 0.57-0.61; P < .01) and endovascular AAA repair (AUC for mFI, 0.60 vs 0.59 and 0.57; 95% CI, 0.58-0.62; P = .01). There were no significant differences in discrimination of class IV complications after open or endovascular PAD or carotid endarterectomy. CONCLUSIONS: The mFI was a better discriminator of mortality than other risk indices; however this was only significant for the open cohort. The mFI was also a better discriminator of class IV complications for the open and endovascular AAA repair groups. These data suggest that mFI should be used in place of previously recognized risk indices to define perioperative mortality after open vascular surgery and risk of major complications after aneurysm repair.

Diabetes does not worsen outcomes following infrageniculate bypass or endovascular intervention for patients with critical limb ischemia.

OBJECTIVE: Both open surgery and endovascular peripheral interventions have been shown to effectively improve outcomes in patients with peripheral arterial disease, but minimal data exist comparing outcomes performed at and below the knee among patients with diabetes (DM) specifically. The purpose of this study is to compare outcomes following open bypass (lower extremity bypass [LEB]) and peripheral vascular intervention (PVI) at and below the knee in patients with DM vs patients without DM (non-DM) with critical limb ischemia. METHODS: Data from the 2008-2014 Vascular Quality Initiative (VQI) were analyzed. All patients undergoing LEB or PVI at or below the knee for rest pain or tissue loss were included. One-year primary patency, major amputation, and mortality were compared for patients with DM vs patients without DM stratified by treatment approach. RESULTS: Overall, 2566 patients were included, including 500 patients (19%) undergoing LEB (DM = 355 vs non-DM = 145) and 2066 patients (81%) undergoing PVI (DM = 1463 vs non-DM = 603). Patients with DM were more frequently black (18% vs 14%), had more comorbidities, and more frequently underwent revascularization for tissue loss (85% vs 58%) compared with patients without DM (all, P < .001). Within the LEB group, there were no significant differences in 1-year primary patency (74% vs 71%; P =.52), major amputation (16% vs 12%; P = .39), or mortality (10% vs 6%; P =.16) between DM vs non-DM patients. There were also no significant differences in 1-year primary patency (81% vs 79%; P = .36), major amputation (14% vs 11%; P =.09) or mortality (6% vs 7%; P =.30) among patients with DM vs patients without DM undergoing PVI. Multivariable analysis adjusting for baseline differences between groups demonstrated a nonsignificant trend toward better primary patency in the DM group following both LEB (hazard ratio, 1.55; 95% confidence interval, 1.00-2.42; P = .05) and PVI (hazard ratio, 1.23; 95% confidence interval, 0.97-1.56; P = .09). There were no significant differences in 1-year major amputation or mortality comparing patients with DM vs patients without DM for either LEB or PVI after risk adjustment (all, P ≥ .16). CONCLUSIONS: Critical limb ischemia resulting from arterial occlusive disease at or below the knee can be treated successfully with either open surgical bypass or endovascular interventions in both DM and non-DM patients. Aggressive attempts at limb salvage among patients with critical limb ischemia should be pursued regardless of DM status.

Thirty-day readmission after lower extremity bypass in diabetic patients.

BACKGROUND: Lower extremity bypass (LEB) for peripheral vascular disease is a common procedure in diabetics and is associated with readmission. Thus, we hypothesized that diabetes might be a predictor of 30-d unplanned readmission after LEB. METHODS: Patients undergoing infrainguinal LEB in the 2011-12 American College of Surgeons National Surgery Quality Improvement Program database were divided into nondiabetics mellitus (NDM), non-insulin-dependent diabetics mellitus (NIDDM), and insulin-dependent diabetic mellitus (IDDM). Univariate and multivariate analyses were used to evaluate the influence of diabetes on 30-d readmission. RESULTS: A total of 9207 patients (5155 [56%] NDM, 1690 (18%) NIDDM, and 2362 (26%) IDDM) underwent LEB. Unplanned readmission was observed in 1448 patients (16%). IDDM had significantly higher crude postoperative complication (43% versus 30% NDM, 36% NIDDM; P < 0.001) and unplanned readmission rates (20% versus 14% NDM, 16% NIDDM; P < 0.001). Concomitant cardiac disease significantly modified the association between diabetes and unplanned readmission. On multivariable analysis, IDDM was an independent predictor of unplanned readmission in the absence of cardiac disease (odds ratio [OR] = 1.23; 95% confidence interval [CI], 1.03-1.47; P = 0.01). However, this association did not remain significant in the presence of cardiac disease (OR = 0.70; 95% CI, 0.48-1.01; P = 0.56). On subgroup analysis of those without cardiac disease, cardiac complications were a significant risk factor for readmission in IDDM (OR = 2.00; 95% CI, 1.12-3.57; P = 0.02) but not NDM (P = 0.31) or NIDDM (P = 0.10). CONCLUSIONS: Although post-LEB unplanned readmission was more common among diabetics, IDDM was independently associated with unplanned readmission only in those without cardiac disease. This was driven, in part, by increased cardiac complications. Therefore, a more stringent preoperative cardiac workup in this group should be considered before LEB.

Gender Predicts Rupture of Pancreaticoduodenal Artery Aneurysms.

BACKGROUND: There remains no consensus on indication or technique for repair of pancreaticoduodenal artery aneurysms (PDAA) due to the fact that they are exceedingly rare. We sought to evaluate risk factors for rupture, as well as compare the outcomes of open and endovascular surgery. METHODS: We performed a retrospective review of all PDAAs over a 15-year period. The primary outcome was technical success, defined as complete cessation of flow within the aneurysm sac on follow-up imaging. Secondary outcomes included complications greater than Clavien-Dindo Grade I. RESULTS: A total of 21 PDAAs was identified (mean size 20 mm, interquartile range 8-32). Eight patients (38%) were male with an average age at diagnosis of 54.3 ± 2.4 years. Aneurysm etiology included degenerative (90%), pancreatitis (14%), and connective tissue disorder (5%). Seven patients (33%) had additional aneurysms on imaging. Ten patients (48%) were asymptomatic, while 5 patients (24%) presented with rupture. Six patients (29%) had an open repair, including 4 aneurysm ligations and 2 emergent Whipple procedures. Eleven patients underwent an endovascular intervention including 10 (48%) embolizations and 1 stent-assisted coiling (9%). Technical success was 100% for the open group and 91% in the endovascular group. Clavien-Dindo grade >1 complications occurred in 67% of open patients and 0% of endovascular patients (P = 0.01). Death occurred in 2 ruptured patients who underwent open repair. On univariate analysis, male gender was statistically associated with rupture (P = 0.02); however, size of the aneurysm was not (P = 0.77). There was a trend toward an increased rupture rate in those with celiac stenosis (P = 0.10). CONCLUSIONS: In one of the largest series of PDAA to date, only male gender was associated with rupture. Furthermore, size of the aneurysm was not associated with rupture and should not be considered a criterion for repair. While technical success was greater in the open group, it was also associated with an increased incidence of clinically significant complications and death. Endovascular aneurysm embolization should be considered the treatment of choice.

Clinical presentation of patients with a thyroid follicular neoplasm: are there preoperative predictors of malignancy?

BACKGROUND: Studies examining differences in presentation of patients with benign [follicular adenoma (FA)] and malignant follicular thyroid neoplasms [follicular thyroid carcinoma (FTC) or follicular variant papillary thyroid carcinoma (FVPTC)] include only one or two of these subtypes, and none has considered clinical, cytological, and sonographic features together. We therefore examined presenting clinical features of all benign and malignant follicular neoplasm subtypes in an attempt to identify predictors of malignancy. METHODS: Consecutive patients with a surgically resected follicular thyroid neoplasm at a tertiary hospital from 2005 to 2013 were reviewed. Age, gender, symptoms, history, physical findings, nodule size, sonographic, cytologic, and final pathologic results were recorded. Multivariate logistic regression was used to determine variables that contributed to a diagnosis of malignant follicular neoplasm. RESULTS: A total of 616 patients (163 males, 453 females) presented with 441 FAs, 17 FTCs, and 158 FVPTCs. On multivariate analysis, male sex [odds ratio (OR) 1.87, p = 0.008], family history of thyroid cancer (OR 5.16, p < 0.001), and history of head and neck radiation (OR 2.01, p = 0.04) were associated with an increased odds of malignancy; age >45 (OR 2.03, p = 0.001), dysphagia (OR 3.48, p = 0.001) or pressure sensation (OR 3.00, p = 003), concomitant hyperthyroidism (OR 4.76, p = 0.01), nodules ≥4 cm (OR 3.68, p < 0.001), and multinodularity on physical examination (OR 1.93, p = 0.004) were associated with an increased odds of a benign lesion. CONCLUSIONS: Independent clinical predictors exist that might be helpful in preoperative differentiation of benign and malignant follicular neoplasms. A combination of these predictors with both FNA and molecular results may help us to improve the clinical management of patients with follicular thyroid lesions.

Comparison of placental pathology between severe preeclampsia and HELLP syndrome.

OBJECTIVE: This study was performed to evaluate and compare the placental pathology in patients with severe pre-eclampsia (PE) and HELLP syndrome. Moreover, neonatal birth weight was compared between the two groups. MATERIALS AND METHODS: This cross-sectional prospective study was conducted in Alzahra and Beheshti Hospitals (Isfahan, Iran) between 2007 and 2009. Placentas from 32 patients having severe pre-eclampsia without HELLP (referred to as preeclampsia group) and 25 patients having severe preeclampsia with HELLP syndrome (referred to as HELLP group) were evaluated. The studied parameters included placental weight, chorioamnionitis (either acute or chronic), retroplacental hematoma, placental infarction, intervillous thrombosis, and decidual arteriopathy. Birth weight adjusted for gestational age was also compared between the two groups. RESULTS: We found statistically more significant frequency of retroplacental hematoma in the PE group compared to the HELLP group (P value 0.00). Despite the relatively high frequency of accelerated villous maturation and decidual arteriopathy in both groups, the difference between the two groups regarding these two parameters was not statistically significant. Other placental features did not show any significant difference between the two groups either. The frequency of small for gestational age births showed no statistically significant difference between the two groups. CONCLUSION: Retroplacental hematoma was the only placental pathology that showed statistically significant different frequencies between the two groups. Although this may suggest different underlying pathogenetic mechanisms in these two conditions, further studies are needed to confirm this hypothesis.

An Option for Shaft-Only Gender-Affirming Phalloplasty: Vaginal Preservation and Vulvoscrotoplasty. A Technical Description.

SUMMARY: Genital masculinizing gender-affirming surgery is a growing field. Because of a spectrum of gender identity, gender expression, sexual expression, patient desires, and patient tolerance for complications, options for surgery vary accordingly. Shaft-only phalloplasty avoids urethral lengthening, but may still be accompanied by hysterectomy, vaginectomy, scrotoplasty, clitoroplasty (burying of the clitoris), glansplasty, and placement of erectile devices and testicular implants. Patients who desire retention of vaginal canal patency are candidates for vaginal preservation vulvoscrotoplasty; however, there is a paucity of literature describing the procedure and its outcomes. In this article, the authors review the technique used by the senior author at Oregon Health and Science University and report surgical outcomes for four patients. Future studies regarding patient-recorded outcome measures, aesthetics, sexual function, urologic function, patient satisfaction, and conversion to other options will help surgeons better understand patients pursuing gender-affirming surgery through shaft-only phalloplasty.

Unusual findings in thyroid cytology and histology.

INTRODUCTION: Although cytology and histopathology of thyroid lesions generally fall into common, well-defined categories, there are uncommon cases with unusual fine needle aspiration (FNA) findings or histology. Herein, we review the prevalence and characteristics of rare thyroid cytology and histopathology findings at a tertiary hospital. METHODS: Institutional data from >31,000 patients with a thyroid pathology from 1995 to 2013 were queried. Both cytology and histology were available in 6,693 patients. After exclusion of the common cytological categories detailed by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and common histopathology categories, 90 patients with either an unusual FNA, histopathology, or both were identified. RESULTS: A total of 90 cases were included (19: only unusual FNA; 25: only unusual histology; 46: both unusual cytology and histopathology). The positive predictive value of an unusual FNA for discovering an unusual lesion was 71% (95% CI: 58%-81%). The majority (66%) were females and median age was 59 years. On histopathology, 80 (88%) cases were malignant, 72 (90%) of which were initially diagnosed as malignant on FNA. Of the 10 benign lesions, 8 (80%) also had a benign FNA. Patients with unusual malignant lesions were significantly older than those with unusual benign lesions (62 vs. 44 years; P: 0.004). CONCLUSION: Unusual cytopathological and histopathological findings in thyroid comprise a varied group of tumors that are individually rare but collectively common. A preoperative FNA with an unusual cytopathology is likely to lead to an unusual histopathological diagnosis; however, its diagnostic accuracy in differentiating benign from malignant is lower than the accuracy of cytopathology of conventional TBSRTC. Diagn. Cytopathol. 2017;45:185-190. © 2016 Wiley Periodicals, Inc.

RAS Mutations, and RET/PTC and PAX8/PPAR-gamma Chromosomal Rearrangements Are Also Prevalent in Benign Thyroid Lesions: Implications Thereof and A Systematic Review.

BACKGROUND: Molecular markers associated with thyroid malignancy are increasingly being used as differential diagnostic tools for thyroid nodules. However, little has been reported recently regarding the prevalence of these markers in benign lesions. The literature was systematically reviewed to examine studies that reported on the prevalence of these markers in benign thyroid lesions. METHODS: Appropriate studies published between January 1, 2000, and April 30, 2015, and cataloged in PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for by combining different keywords for "thyroid tumor" with both general and specific keywords for "molecular marker" by using "AND" as the Boolean operator. All studies meeting criteria that reported the prevalence of RAS mutations, and RET/PTC and PAX8/PPAR-gamma chromosomal rearrangements in benign thyroid lesions were included for study. RESULTS: A total of 64 articles (including 8162 patients, of whom 42.5% had benign lesions) that met all the study criteria were systematically reviewed and abstracted. Among 35 studies examining RAS mutations, the reported prevalence of RAS mutation in benign lesions ranged from 0% to 48%. In 38 studies examining RET/PTC rearrangements, the prevalence in benign lesions ranged from 0% to 68%. PAX8/PPAR-gamma rearrangements were examined in 27 studies, with the prevalence in benign lesions ranging from 0% to 55%. CONCLUSION: The presence of these biomarkers and the tremendous variation in reports of their prevalence in benign lesions suggests the need for caution when including these markers in diagnostic decisions. Further understanding of the importance of these markers, as well as newly discovered markers of thyroid malignancy, may be required in order to avoid overtreatment of patients with benign thyroid tumors.

Parathyroid surgery can be safely performed in a community hospital by experienced parathyroid surgeons: A retrospective cohort study.

BACKGROUND: There is ongoing debate about the effectiveness and safety of performing parathyroid surgery in low-volume community hospitals. STUDY DESIGN/METHODS: Cases performed at community hospital by a group of 4 parathyroid surgeons (group 1) were reviewed. Cure and complication rates were analyzed in light of outcomes of an expert endocrine surgeon from high-volume academic center (group 2) as point of reference. RESULTS: During the respective time periods, 204 patients met inclusion criteria in group1 and 218 patients in group 2. Patient characteristics, biochemical tests, and performed localizing studies (ultrasound and sestamibi scan) were comparable between the two groups. Pathological findings, including adenoma, double adenoma, hyperplasia, and cancer were comparable. Each had comparable cure rates (97% and 99%) (p < 0.18) and complication rates (1% and 1%) (p < 0.93) for group 1 and 2, respectively. CONCLUSION: Our results showed that experienced parathyroid surgeons will achieve comparable excellent outcomes of parathyroid surgery at both community and academic-based centers. As the field of endocrine surgery evolves and matures, producing young fellowship-trained endocrine surgeons, there will be growing need for expanding the niche of endocrine surgery into community-based hospital settings, which eventually will contribute to expanding and equalizing access to high-quality surgical care across urban and rural areas.

Evaluation of the Effect of Diagnostic Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules.

IMPORTANCE: Diagnostic molecular testing is used in the workup of thyroid nodules. While these tests appear to be promising in more definitively assigning a risk of malignancy, their effect on surgical decision making has yet to be demonstrated. OBJECTIVE: To investigate the effect of diagnostic molecular profiling of thyroid nodules on the surgical decision-making process. DESIGN, SETTING, AND PARTICIPANTS: A surgical management algorithm was developed and published after peer review that incorporated individual Bethesda System for Reporting Thyroid Cytopathology classifications with clinical, laboratory, and radiological results. This algorithm was created to formalize the decision-making process selected herein in managing patients with thyroid nodules. Between April 1, 2014, and March 31, 2015, a prospective study of patients who had undergone diagnostic molecular testing of a thyroid nodule before being seen for surgical consultation was performed. The recommended management undertaken by the surgeon was then prospectively compared with the corresponding one in the algorithm. Patients with thyroid nodules who did not undergo molecular testing and were seen for surgical consultation during the same period served as a control group. MAIN OUTCOMES AND MEASURES: All pertinent treatment options were presented to each patient, and any deviation from the algorithm was recorded prospectively. To evaluate the appropriateness of any change (deviation) in management, the surgical histopathology diagnosis was correlated with the surgery performed. RESULTS: The study cohort comprised 140 patients who underwent molecular testing. Their mean (SD) age was 50.3 (14.6) years, and 75.0% (105 of 140) were female. Over a 1-year period, 20.3% (140 of 688) had undergone diagnostic molecular testing before surgical consultation, and 79.7% (548 of 688) had not undergone molecular testing. The surgical management deviated from the treatment algorithm in 12.9% (18 of 140) with molecular testing and in 10.2% (56 of 548) without molecular testing (P = .37). In the group with molecular testing, the surgical management plan of only 7.9% (11 of 140) was altered as a result of the molecular test. All but 1 of those patients were found to be overtreated relative to the surgical histopathology analysis. CONCLUSIONS AND RELEVANCE: Molecular testing did not significantly affect the surgical decision-making process in this study. Among patients whose treatment was altered based on these markers, there was evidence of overtreatment.

Association of BRAF V600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers.

BACKGROUND: Studies have demonstrated an association of the BRAF(V600E) mutation and microRNA (miR) expression with aggressive clinicopathologic features in papillary thyroid cancer (PTC). Analysis of BRAF(V600E) mutations with miR expression data may improve perioperative decision making for patients with PTC, specifically in identifying patients harboring central lymph node metastases (CLNM). METHODS: Between January 2012 and June 2013, 237 consecutive patients underwent total thyroidectomy and prophylactic central lymph node dissection (CLND) at four endocrine surgery centers. All tumors were tested for the presence of the BRAF(V600E) mutation and miR-21, miR-146b-3p, miR-146b-5p, miR-204, miR-221, miR-222, and miR-375 expression. Bivariate and multivariable analyses were performed to examine associations between molecular markers and aggressive clinicopathologic features of PTC. RESULTS: Multivariable logistic regression analysis of all clinicopathologic features found miR-146b-3p and miR-146b-5p to be independent predictors of CLNM, while the presence of BRAF(V600E) almost reached significance. Multivariable logistic regression analysis limited to only predictors available preoperatively (molecular markers, age, sex, and tumor size) found miR-146b-3p, miR-146b-5p, miR-222, and BRAF(V600E) mutation to predict CLNM independently. While BRAF(V600E) was found to be associated with CLNM (48% mutated in node-positive cases vs. 28% mutated in node-negative cases), its positive and negative predictive values (48% and 72%, respectively) limit its clinical utility as a stand-alone marker. In the subgroup analysis focusing on only classical variant of PTC cases (CVPTC), undergoing prophylactic lymph node dissection, multivariable logistic regression analysis found only miR-146b-5p and miR-222 to be independent predictors of CLNM, while BRAF(V600E) was not significantly associated with CLNM. CONCLUSION: In the patients undergoing prophylactic CLNDs, miR-146b-3p, miR-146b-5p, and miR-222 were found to be predictive of CLNM preoperatively. However, there was significant overlap in expression of these miRs in the two outcome groups. The BRAF(V600E) mutation, while being a marker of CLNM when considering only preoperative variables among all histological subtypes, is likely not a useful stand-alone marker clinically because the difference between node-positive and node-negative cases was small. Furthermore, it lost significance when examining only CVPTC. Overall, our results speak to the concept and interpretation of statistical significance versus actual applicability of molecular markers, raising questions about their clinical usefulness as individual prognostic markers.

Conventional smears versus liquid-based preparations for thyroid fine-needle aspirates: a systematic review and meta-analysis.

INTRODUCTION: Thyroid fine-needle aspiration has traditionally been prepared using conventional smears (CS). Liquid-based preparations (LBP) have grown in popularity and yet, there is a lack of consensus about which method is superior. This review compared CS and LBP as an intervention in the management of thyroid nodules. MATERIALS AND METHODS: Medline, EMBASE, Scopus and ClinicalTrials.gov were searched to locate relevant studies. Observational studies comparing CS and LBP of consecutive thyroid fine-needle aspirations were included. Two reviewers independently screened, extracted, and entered data. Double data extraction included the following outcomes: (1) the proportion of inadequate smears and (2) the proportion of indeterminate smears. Studies were also assessed for risk of bias and heterogeneity. RESULTS: From 599 unique studies, title/abstract screening identified 136 studies, and full text screening identified 13 studies. The 13 studies included 24,307 fine-needle aspirations from 19,433 patients and had high clinical, methodological, and statistical heterogeneity with low risk of bias. For CS and LBP, a meta-analysis of 12 studies showed no difference in the proportion of inadequate smears (risk difference: -0.00; 95% confidence interval [CI]: -0.04-0.04); 13 studies showed no difference in the proportion of indeterminate smears (risk difference: -0.02; 95% CI: -0.05-0.01). Sensitivity analysis of studies with low risk of bias had similar results. CONCLUSIONS: There is no difference between CS and LBP in the proportion of inadequate and indeterminate smears. Recommendations of one method over the other should be based on cost, feasibility, and accuracy, all of which require further study.

Malignancy risk and reproducibility associated with atypia of undetermined significance on thyroid cytology.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) describes several subcategories within atypia of undetermined significance (AUS), including (1) presence of focal nuclear atypia (AUS-N), (2) focal microfollicular proliferation (AUS-F), (3) focal Hürthle cell proliferation (AUS-HC), and (4) other (AUS-O). Several publications suggest that 5-15% is an underestimate of the malignancy risk for AUS, and that the underestimation is owing to the similarity between AUS-N and suspicious for malignancy (SFM). Thus, we investigated the AUS subcategories during morphologic re-review at a tertiary care center and their associated malignancy risk. METHODS: Of 4,827 fine-needle aspiration specimens were sent between January 2009 and August 2013 for morphologic re-review, 806 were categorized as AUS. Comparison of AUS subcategory diagnoses were made between outside and re-review results. The malignancy risk was also determined for 255 nodules with available surgical pathology. RESULT: The outside diagnoses of the 806 cases read as AUS on second review were as follows: 5 insufficient (0.1%), 149 benign (19%), 463 AUS (57%), 124 SFN or suspicious for follicular or Hürthle cell neoplasm (15%), 56 SFM (7%), and 9 malignant (1%). Of the 463 cases in which both the outside and re-review diagnosis was AUS, the distribution of the subcategories in order of increasing frequency was 53 AUS-HC (11%), 74 AUS-O (16%), 79 AUS-F (17%), and 257 AUS-N (56%). Of the 255 resected nodules, 99 (39%) were malignant. Subcategory malignancy rates were: AUS-HC, 19% (9/47); AUS-O, 26% (14/54); AUS-F, 39% (19/49); and AUS-N, 54% (57/105). Cases in which both the referring institution and re-review agreed about the AUS-N subcategory had an even greater risk of malignancy (68%; 17/25). CONCLUSION: Disagreement about the diagnosis of AUS between institutions is frequent. The malignancy risk for AUS is higher than originally proposed by TBSRTC and attributable to the high risk of AUS-N. Furthermore, agreement on AUS-N after re-review portends a malignancy risk that borders on that of SFM. This suggests that AUS-N may have discrete features that can provide specific morphologic predictors and enable the consolidation of AUS-N into SFM.

Comparison study on effectiveness of pentoxifyllin with LD to prevent recurrent endometriosis.

BACKGROUND: About 75% of the symptomatic patients who involved with endometriosis have pelvic pain and dysmenorrhea. Pentoxifyllin is one of the drugs that according to its mechanism could be effective for pain relief of endometriosis which has been used for endometriosis treatment recently. OBJECTIVE: We conducted a comparative study for detecting the effect of pentoxifylin (as an immonomodelator) in preventing recurrence endometriotic pain with pentoxifylin plus a combined contraceptive pill with low dose estrogen (LD) and also the LD pill alone. MATERIALS AND METHODS: This was a comparative clinical trial on 83 patients with the chief complaint (CC) of pain (dysmenorrheal /or pelvic pain) and with the end diagnosis of endometriosis, in an operative laparoscopy. Patients, dividing to 3 groups, were treated with pentoxifylin, pentoxifylin+LD and LD alone for 10 months. The severity of pain (dismenorhea and/or pelvic pain) was detected by visual analogue scale (VAS) before and after the treatment. The severity of endometriosis in the patients was: I in class I and II in class II and III in class III. The groups were matched for the pain. The number of the patients in group 1, 2 and 3 were 28, 28 and 27 respectively. RESULTS: The pain was reduced in the groups of pentoxifylin+LD (p<0.001) and LD alone (p=0.00). The pain relief was not significant in the group of pentoxifylin alone (p=0.136). After treatment, the severity of pain was not significantly different between the LD group and the LD+penthoxyfillin group, but there was difference between these two groups and the group of penthoxyfillin alone. CONCLUSION: This study showed that penthoxyfillin actually could not have any effect on the pain relief of endometriosis. It also made it clear that penthoxyfillin could not increase the efficacy of LD when used with this medication.