Racial and Ethnic Disparities in Operative Experience Among General Surgery Residents: A Multi-Institutional Study from the US ROPE Consortium.

OBJECTIVE: To determine the relationship between race/ethnicity and case volume among graduating surgical residents. BACKGROUND: Racial/ethnic minority individuals face barriers to entry and advancement in surgery; however, no large-scale investigations of the operative experience of racial/ethnic minority residents have been performed. METHODS: A multi-institutional retrospective analysis of the Accreditation Council for Graduate Medical Education case logs of categorical general surgery residents at 20 programs in the US Resident OPerative Experience Consortium database was performed. All residents graduating between 2010 and 2020 were included. The total, surgeon chief, surgeon junior, and teaching assistant case volumes were compared between racial/ethnic groups. RESULTS: The cohort included 1343 residents. There were 211 (15.7%) Asian, 65 (4.8%) Black, 73 (5.4%) Hispanic, 71 (5.3%) "Other" (Native American or Multiple Race), and 923 (68.7%) White residents. On adjusted analysis, Black residents performed 76 fewer total cases (95% CI, -109 to -43, P <0.001) and 69 fewer surgeon junior cases (-98 to -40, P <0.001) than White residents. Comparing adjusted total case volume by graduation year, both Black residents and White residents performed more cases over time; however, there was no difference in the rates of annual increase (10 versus 12 cases per year increase, respectively, P =0.769). Thus, differences in total case volume persisted over the study period. CONCLUSIONS: In this multi-institutional study, Black residents graduated with lower case volume than non-minority residents throughout the previous decade. Reduced operative learning opportunities may negatively impact professional advancement. Systemic interventions are needed to promote equitable operative experience and positive culture change.

Disparities in the Operative Experience Between Female and Male General Surgery Residents: A Multi-institutional Study From the US ROPE Consortium.

OBJECTIVE: To examine differences in resident operative experience between male and female general surgery residents. BACKGROUND: Despite increasing female representation in surgery, sex and gender disparities in residency experience continue to exist. The operative volume of male and female general surgery residents has not been compared on a multi-institutional level. METHODS: Demographic characteristics and case logs were obtained for categorical general surgery graduates between 2010 and 2020 from the US Resident OPerative Experience Consortium database. Univariable, multivariable, and linear regression analyses were performed to compare differences in operative experience between male and female residents. RESULTS: There were 1343 graduates from 20 Accreditation Council for Graduate Medical Education-accredited programs, and 476 (35%) were females. There were no differences in age, race/ethnicity, or proportion pursuing fellowship between groups. Female graduates were less likely to be high-volume residents (27% vs 36%, P < 0.01). On univariable analysis, female graduates performed fewer total cases than male graduates (1140 vs 1177, P < 0.01), largely due to a diminished surgeon junior experience (829 vs 863, P < 0.01). On adjusted multivariable analysis, female sex was negatively associated with being a high-volume resident (OR = 0.74, 95% CI: 0.56 to 0.98, P = 0.03). Over the 11-year study period, the annual total number of cases increased significantly for both groups, but female graduates (+16 cases/year) outpaced male graduates (+13 cases/year, P = 0.02). CONCLUSIONS: Female general surgery graduates performed significantly fewer cases than male graduates. Reassuringly, this gap in operative experience may be narrowing. Further interventions are warranted to promote equitable training opportunities that support and engage female residents.

Impact of Obesity on Risk of Hypocalcemia After Total Thyroidectomy: Targeted National Surgical Quality Improvement Program Analysis of 16,277 Patients.

INTRODUCTION: Hypocalcemia following total thyroidectomy (TT) is common due to postoperative parathyroid dysfunction and vitamin D deficiency. Given the association between obesity and vitamin D deficiency, we sought to correlate body mass index (BMI) with hypocalcemia after TT. METHODS: Patients undergoing TT between 2016 and 2020 were identified from the American College of Surgeons National Surgical Quality Improvement Program thyroidectomy-targeted database. Univariable and multivariable regressions, stratified by BMI category (normal, overweight, obese), identified factors associated with hypocalcemia prior to discharge, within 30 d, and severe hypocalcemic events (emergent evaluation, intravenous calcium supplementation, or readmission). RESULTS: Sixteen thousand two hundred seventy seven TT were performed with available BMI data. Three thousand five hundred thirty one (21.7%) patients had normal BMI, 4823 (29.6%) were overweight, and 7772 (47.7%) were obese. Patients with BMI ≥ 25 had decreased risk of hypocalcemia before discharge (9.8% versus 13%, odds ratio [OR] 0.73, P < 0.001), 30 d (8.1% versus 10.4%, OR 0.76, P < 0.001), and severe hypocalcemic events (5.5% versus 6.4%, OR 0.84, P = 0.029) compared to normal BMI patients. On multivariable analysis for normal BMI patients, age < 45 y was a risk factor for hypocalcemia before discharge, 30 d, and severe hypocalcemic events (P < 0.05 for all). Additional risk factors in this group for 30-d hypocalcemia included parathyroid autotransplant and central neck dissection (P < 0.05) and recurrent laryngeal nerve injury for severe hypocalcemic events (P = 0.01). CONCLUSIONS: Younger patients with BMI < 25 are at an increased risk for hypocalcemia and severe hypocalcemic events after TT. These patients may benefit from preoperative counseling and increased calcium/vitamin D supplementation to reduce prolonged hospitalization and mitigate morbidity.

Gender Disparities in Presentations at the Society of Surgical Oncology (SSO) Meetings From 2014 to 2019.

BACKGROUND: Participation in surgical society meetings serves as a proxy for academic success and is important for career development. This study aimed to investigate and report the gender breakdown of presenters at recent Society of Surgical Oncology (SSO) meetings. METHODS: Genders of presenters for poster, parallel, plenary, and video sessions at SSO meetings from 2014 through 2019 were collected. These data were broken down to first-last authorship relationships including female-female, female-male, male-female, and male-male. The proportions of female-to-male presenters were compared for each session type. Statistical significance was set at p value lower than 0.05. RESULTS: From 2014 through 2019, the SSO had 2920 presenters, and 47% were female. Women were listed as first authors more often for the poster session (48%) than for other sessions (parallel, plenary, and video) (p = 0.003). Women also were listed more often as senior authors for the poster session (31%) than for other sessions (p = 0.004). Female senior authors were fewer than male senior authors across all session types. Female first authors had the highest representation in breast (75%), endocrine (48%), and cutaneous (46%) specialties (p < 0.001). The most common combination of first and senior authors was male-male (43%), followed by female-male (28%), female-female (19%), and male-female (10%). CONCLUSION: Overall, female presentation at SSO is comparable with society demographics, and female first authorship is relatively equal to male first authorship in poster sessions. Whereas female first authorship improved over time, female senior authorship remained relatively flat. Opportunities to improve gender equality in senior authorship positions should be explored.

Gender and Racial/Ethnic Disparities in Operative Volumes of Graduating General Surgery Residents.

INTRODUCTION: Gender disparities in resident operative experience have been described; however, their etiology is poorly understood, and racial/ethnic disparities have not been explored. This study investigated the relationship between gender, race/ethnicity, and surgery resident case volumes. MATERIALS AND METHODS: A retrospective analysis of graduating general surgery resident case logs (2010-2020) at an academic medical center was performed. Self-reported gender and race/ethnicity data were collected from program records. Residents were categorized as underrepresented in medicine (URM) (Black, Hispanic, Native American) or non-URM (White, Asian). Associations between gender and URM status and major, chief, and teaching assistant (TA) mean case volumes were analyzed using t-tests. RESULTS: The cohort included 80 residents: 39 female (48.8%) and 17 URM (21.3%). Compared to male residents, female residents performed fewer TA cases (33 versus 47, P < 0.001). Compared to non-URM residents, URM residents graduated with fewer major (948 versus 1043, P = 0.008) and TA cases (32 versus 42, P = 0.038). Male URM residents performed fewer TA cases than male non-URM residents (32 versus 50, P = 0.031). Subanalysis stratified by graduation year demonstrated that from 2010 to 2015, female residents performed fewer chief (218 versus 248, P = 0.039) and TA cases (29 versus 50, P = 0.001) than male residents. However, from 2016 to 2020, when gender parity was achieved, no significant associations were observed between gender and case volumes. CONCLUSIONS: Female and URM residents perform fewer TA and major cases than male non-URM residents, which may contribute to reduced operative autonomy, confidence, and entrustment. Prioritizing gender and URM parity may help decrease case volume gaps among underrepresented residents.

Increased Body Mass Index is Associated With Lower Risk of Hypocalcemia in Total Thyroidectomy Patients.

INTRODUCTION: Hypocalcemia following total thyroidectomy is common due to postoperative parathyroid dysfunction. We sought to identify the impact of obesity on postthyroidectomy hypocalcemia. METHODS: We performed a single-center retrospective study of all total thyroidectomies performed from 2016 to 2019 after implementation of an updated calcium supplementation protocol. Patient characteristics and outcomes were measured including body mass index (BMI), postoperative hypocalcemia (Ca <8.3), and hypocalcemic symptoms. RESULTS: Overall, 559 total thyroidectomies were performed. A total of 146 patients (26.2%) developed hypocalcemia requiring supplementation adjustment and 116 patients (20.8%) developed mild hypocalcemia symptoms. On multivariable analysis, younger patients, patients with lower preoperative calcium, and lower BMI were more likely to develop postoperative hypocalcemia (all P < 0.05). Similarly, younger patients and patients with BMI <25 were more likely to develop hypocalcemic symptoms (all P < 0.05). CONCLUSIONS: Younger age and lower BMI were associated with increased risk of hypocalcemia after total thyroidectomy. These patients may benefit from preoperative and/or increased postoperative supplementation.

Completion Thyroidectomy is Less Common Following Updated 2015 American Thyroid Association Guidelines.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines recommended that low-risk, differentiated thyroid cancers (DTC) between 1 and 4 cm may be treated with thyroid lobectomy alone. We sought to determine the effect of these guideline changes on the rate of completion thyroidectomy (CT) for low-risk DTC and factors influencing surgical decision-making. METHODS: All patients from 2014 to 2018 who received an initial thyroid lobectomy at our institution with final pathology demonstrating DTC were included. Patients were divided into "pre" and "post" guideline cohorts (2014-2015 and 2016-2018, respectively). The rate of CT was compared between the two cohorts. Patient demographics and tumor characteristics were examined for association with CT. RESULTS: A total of 163 patients met study criteria: 63 patients in the 2014-2015 ("pre") and 100 in the 2016-2018 ("post") group. In the "pre" period, 41 (65.1%) patients received CT compared with 43 (43.0%) in the "post" period (p < 0.01)-a 34% decrease in the rate of completion surgery (p < 0.01). Of low-risk patients with DTC between 1 and 4 cm in size, 17 of 35 (48.6%) received CT in the "pre" period compared with 15 of 60 (25.0%) in the post period-a 48.6% decrease in the rate of completion surgery (p = 0.02). Greater tumor size, capsular invasion, and multifocality were associated with CT in low-risk "post" guideline patients (p < 0.05 for all). CONCLUSIONS: The rate of CT decreased significantly by 48.6% for low-risk patients with DTC between 1 and 4 cm, demonstrating recognition of the 2015 ATA guidelines. However, 25% of these patients underwent CT, suggesting additional factors influencing the decision for further treatment.

A potential diagnostic pitfall for hobnail variant of papillary thyroid carcinoma.

AIMS: Hobnail variant of papillary thyroid carcinoma (PTC) is an aggressive PTC subtype characterised by a hobnail cytomorphology. However, some classic PTC have a 'hobnail-like' cytomorphology associated with thick, hyalinised, variably oedematous fibrovascular cores that appears to be a form of ischaemic/degenerative atypia. METHODS AND RESULTS: We studied three cohorts to compare the histopathological characteristics and clinical outcome of 'hobnail-like' classic PTC and true hobnail variant of PTC: cohort 1, PTC consecutively resected between 2016 and 2017 (to assess frequency of 'hobnail-like' cytomorphology); cohort 2, 20 'hobnail-like' classic PTC resected between 2005 and 2007 (to assess clinical outcome); and cohort 3, seven true hobnail variant of PTC. A 'hobnail-like' cytomorphology was identified in 16% of consecutively resected PTC. Compared with true hobnail variant, 'hobnail-like' classic PTC occurred in younger patients (mean age 40 years versus 68 years, P < 0.001), were smaller tumours (mean tumour size 2.1 cm versus 4.4 cm, P < 0.001), had a lower rate of gross extrathyroidal extension (0% versus 71%, P < 0.001), had a lower proliferative rate (≥3 mitoses per 10 high-power fields seen in 0% versus 71%, P < 0.001; Ki67 index ≥5% in 0% versus 86%, P < 0.001), a lower rate of secondary pathogenic mutations (for cases with molecular data, 0% versus 100%, P = 0.0061) and improved survival (for cases with sufficient clinical outcome data, 10-year disease-free survival of 93% versus 0%, P = 0.0016). CONCLUSION: Classic PTC can show ischaemic/degenerative atypia that mimics the hobnail cytomorphology of true hobnail variant; however, these tumours lack aggressive histopathological features and pursue an indolent clinical course.

Gender Differences in Surgeon Burnout and Barriers to Career Satisfaction: A Qualitative Exploration.

BACKGROUND: Physician burnout is a highly prevalent issue in the surgical community. Burnout is associated with poor career satisfaction; female gender, and younger age place surgeons at higher risk for burnout. Here, we examined drivers behind burnout and career dissatisfaction in female and junior surgical faculty, with specific attention paid to gender-based differences. MATERIALS AND METHODS: Participants included full-time surgery faculty members at a single academic surgery center. Both male and female faculty members were included, at ranks ranging from instructor to associate professor. Semistructured interviews were conducted by a faculty member at the institution until thematic saturation was reached. Field notes were compiled from each interview, and these data were coded thematically. RESULTS: Fourteen female faculty and nine male faculty members were interviewed. For both female and male faculty, lack of control with work life was a significant theme contributing to burnout. Positive factors contributing to career satisfaction for both genders included enjoyment of patient care and teaching, teamwork and collegiality, and leadership support. For female faculty, the major theme of gender bias in the workplace as a risk factor for burnout was prominent. Male faculty struggled more than their female counterparts with guilt over complications and second victim syndrome. CONCLUSIONS: Gender differences driving career dissatisfaction and burnout exist between female and male surgical faculty. Acknowledging these differences when designing efforts to address physician wellness and decrease burnout is critical.

Identification of Specific Educational Targets to Improve the Student Surgical Clerkship Experience.

BACKGROUND: This study describes the relationship between medical student perception of surgery, frequency of positive surgery clerkship activities, and overall surgical clerkship experience. METHODS: Medical students at four academic hospitals completed pre- and post-clerkship surveys assessing 1) surgery clerkship activities/experiences and 2) perceptions of surgery during the 2017-2018 academic year. RESULTS: Ninety-one percent of students completed both a pre- and post-clerkship survey (n = 162 of 179). Student perception of surgery significantly improved across the clerkship overall (P < 0.0001) and for 7 of 21 specific items. Eighty-six percent of students agreed that the clerkship was a meaningful experience. Sixty-six percent agreed that the operating room was a positive learning environment. Multivariable logistic regression identified one-on-one mentoring from a resident (OR [95% CI] = 2.12 [1.11-4.04], P = 0.02) and establishing a meaningful relationship with a surgical patient (OR = 2.21 [1.12-4.37], P = 0.02) as activities predictive of student agreement that the surgical clerkship was meaningful. Making an incision (OR = 2.92 [1.54-5.56], P = 0.001) and assisting in dissection (OR = 1.67 [1.03-2.69], P = 0.035) were predictive of student agreement that the operating room was a positive learning environment. Positive student perception of surgery before the clerkship was associated with increased frequency of positive clerkship activities including operative involvement (r = 0.26, P = 0.001) and relationships with surgical attendings (r = 0.20, P = 0.01), residents (r = 0.41, P < 0.0001), and patients (r = 0.24, P = 0.003). CONCLUSIONS: Interventions to improve surgery clerkship quality should target enhancing student relationships with residents and surgical patients as well as providing opportunity for student operative involvement beyond just suturing. In addition, fostering positive perceptions of surgery in the preclinical period may increase meaningfulness and experience with the later surgery clerkship.

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.

Utility of Level III Axillary Node Dissection in Melanoma Patients with Palpable Axillary Lymph Node Disease.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial II results suggest that future radical axillary lymphadenectomy (ALND) will be performed for bulkier metastatic disease. The utility of level III lymph node (LN) dissection in melanoma patients with palpable metastatic axillary disease was assessed. METHODS: We performed a retrospective chart review of patients who underwent ALND (levels I-III) for metastatic melanoma from 2005 to 2017. We assessed the frequency of level III positive nodes in patients undergoing radical axillary lymphadenectomy (ALND) for metastatic melanoma as well as the prognostic role and factors predictive of level III LN positivity. RESULTS: A total of 190 patients underwent ALND during the study period. Of these, 85 patients had palpable axillary disease, of which 71 had separate level III pathologic assessment. Level III LNs were positive in 16.9% of patients with palpable disease versus 0% with positive sentinel LN. The 1-, 3-, and 5-year overall survival (OS) for patients with palpable disease was 82.9%, 58.9%, and 39.0%, respectively. Median disease-free survival was 26.8 months, and the axillary recurrence rate was 8.2%. High level I/II LN ratio, BRAF mutation, and total LN examined were significant predictors of level III positivity (all p ≤ 0.05). Patients with positive level III LN had significantly worse OS (median 18.6 months vs. not reached, p = 0.001). No preoperative factors were predictive of level III LN positivity. CONCLUSIONS: Level III axillary disease is not uncommon in melanoma patients with clinically palpable nodal disease and provides useful prognostic information for OS. We recommend that full level I-III ALND be considered in this patient cohort.

Effect of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) on Malignancy Rates in Thyroid Nodules: How to Counsel Patients on Extent of Surgery.

PURPOSE: To investigate the impact of the nomenclature change to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) on reported malignancy rates following thyroidectomy. METHODS: Retrospective cohort study of patients with thyroid nodules sampled preoperatively with fine-needle aspiration (FNA) and subsequently removed at one tertiary-care hospital from 4/2016 to 2/2017. Surgical procedure, anatomic pathology, thyroid cytopathology classification, and demographic characteristics were recorded. RESULTS: Thyroidectomy was performed in 353 patients. Twenty-six patients (7.3%) had NIFTP on anatomic pathology. Preoperative FNA demonstrated atypia of undetermined significance (AUS/Bethesda III) in 13 (50%), suspicious for malignancy (SUS/Bethesda V) in 6 (23%), suspicious for follicular neoplasm (SFN/Bethesda IV) in 4 (15%), benign/Bethesda I in 2 (8%), and malignant/Bethesda VI in 1 (4%). Invasive malignancy rates across cytologic categories changed as follows: benign (n = 74) from 4 to 1%, AUS (n = 85) from 33 to 18% (p < 0.05), SFN (n = 58) from 29 to 22%, SUS (n = 33) from 91 to 73% (p < 0.05), and malignant (n = 99) from 99 to 98%. Overall decrease in invasive malignancy was 7.3% for the entire population and 13.1% for indeterminate preoperative FNA cytology (Bethesda III-V). Among 26 NIFTP patients, 17 had thyroid lobectomy (TL) and 9 underwent total thyroidectomy (TT). Eight of the nine patients with TT could have been definitively treated with TL, an 89% decrease. CONCLUSIONS: The NIFTP nomenclature change led to an overall decrease in the malignancy rate at our institution, especially for Bethesda III-V categories. Patients may be counseled toward more conservative surgical options if NIFTP is in the differential.

The Posterior Adiposity Index: A Quantitative Selection Tool for Adrenalectomy Approach.

BACKGROUND: Objective criteria are lacking to determine whether a laparoscopic transabdominal (LA) or retroperitoneoscopic (RP) approach to adrenalectomy is optimal. We hypothesized that imaging characteristics could predict patients for whom RP adrenalectomy is the optimal approach. MATERIALS AND METHODS: Retrospective cohort study of all patients undergoing minimally invasive adrenalectomy between 2014 and 2016 (n = 113) at one institution. Imaging measurements included distances between the skin and Gerota's fascia (S-GF), upper borders of adrenal and kidney (A-K), adrenal and 12th rib (A-R), 12th rib and iliac crest (R-IC), and perinephric fat (PNF). These characteristics plus patient body mass index, gender, age, tumor size, and diagnosis were compared with operative time and estimated blood loss using Pearson's correlation or ANOVA. Multivariable linear regression also identified independent predictors of operative time. RESULTS: Half of patients underwent LA (n = 57) and RP adrenalectomy (n = 56). Median age was 57 y; 60% were female. Mean tumor size was 3.2 cm. Higher body mass index patients were more likely to undergo LA (P = 0.03). Increasing lesion size modestly correlated with longer operative time (r = 0.341). On bivariate analysis, S-GF and PNF distances moderately correlated with operative time (r = 0.464 and 0.494) for RP procedures. The sum of S-GF and PNF generated a Posterior Adiposity Index (PAI). The PAI strongly correlated with operative time for RP (r = 0.590). Nothing was significantly associated with estimated blood loss. Multivariate analysis revealed larger lesions (P = 0.025) and increasing PAI (P = 0.019) were predictive of longer operative time, with PAI ≥9 conferring the greatest risk (P = 0.004). CONCLUSIONS: Smaller tumors and PAI <9 are associated with shorter operative times in RP adrenalectomy. Surgeons can utilize preoperative images to calculate the PAI and determine whether an RP approach would be favorable.

Sorafenib inhibits proliferation and invasion in desmoid-derived cells by targeting Ras/MEK/ERK and PI3K/Akt/mTOR pathways.

Desmoid tumors (DTs) are unusual neoplasms of mesenchymal origin that exhibit locally invasive behavior. Surgical resection is the initial treatment of choice for DTs. For patients with recurrent or unresectable disease, however, medical options are limited. Sorafenib is a multikinase inhibitor with known antitumor activity in various cancers via suppression of the PI3K/Akt/mTOR pathway. Here, we examined the effects of sorafenib on patient-derived DT cell lines, with the aim of characterizing the efficacy and molecular mechanism of action. Early passage DT-derived cells were treated with increasing doses of sorafenib (0-10 µM) and demonstrated up to 90% decrease in proliferation and invasion relative to controls. Signaling arrays identified multiple potential targets of sorafenib in the Ras/MEK/ERK and PI3K/Akt/mTOR signaling cascades. Immunoblot analysis revealed that sorafenib inhibited Akt, MEK and ERK phosphorylation, and this effect correlated with inhibition of total Akt and total MEK, while total ERK levels remained unchanged. Sorafenib also inhibited 4E-BP1 phosphorylation, and this effect correlated with decrease of p-eIF4E and total eIF4E. Finally, in combination with the mammalian target of rapamycin (mTOR) inhibitor everolimus, sorafenib decreased phosphorylation of the ribosomal protein and mTOR effector S6K in an additive manner. Taken together, our results suggest that sorafenib suppresses DT proliferation and invasion via inhibition of Ras/MEK/ERK and PI3K/Akt/mTOR signaling pathways with additional effects on translation. Sorafenib may be a promising therapeutic option in the treatment of DTs. Additional studies in DT patients are warranted to examine the efficacy of combination therapy using sorafenib.

4D-CT is Superior to Ultrasound and Sestamibi for Localizing Recurrent Parathyroid Disease.

BACKGROUND: Recurrent primary hyperparathyroidism (PHPT) presents a diagnostic challenge in localizing a hyperfunctioning gland. Although several imaging modalities are available for preoperative localization, 4D-CT is increasingly utilized for its ability to locate both smaller and previously unlocalized lesions. Currently, there is a paucity of data evaluating the utility of 4D-CT in the reoperative setting compared with ultrasound (US) and sestamibi. We aimed to determine the sensitivity of 4D-CT in localizing parathyroid adenomas in recurrent or persistent PHPT. METHODS: We performed a retrospective review of prospectively collected data from a tertiary-care hospital, and identified 58 patients who received preoperative 4D-CT with US and/or sestamibi between May 2008 and March 2016. Data regarding the size, shape, and number of parathyroid lesions were collected for each patient. RESULTS: A total of 62 lesions were identified intraoperatively among the 58 patients (6 with multigland disease) included in this investigation. 4D-CT missed 13 lesions identified intraoperatively, compared with 32 and 22 lesions missed by US and sestamibi, respectively. Sensitivity for correct lateralization of culprit lesions was 77.4% for 4D-CT, 38.5% for US, and 46% for sestamibi. 4D-CT was superior in lateralizing adenomas (49/62) compared with US (20/52; p < 0.001) and sestamibi (18/47; p < 0.001). The overall cure rate (6-month postoperative calcium < 10.7 mg/dL) was 89.7%. All patients with lesions correctly lateralized by 4D-CT were cured at 6 months. CONCLUSION: 4D-CT localized parathyroid adenomas with higher sensitivity among patients with recurrent or persistent PHPT compared with sestamibi or US-based imaging.

Reasons Associated with Total Thyroidectomy as Initial Surgical Management of an Indeterminate Thyroid Nodule.

BACKGROUND: Diagnostic hemithyroidectomy (HT) is the most widely recommended surgical procedure for a nodule with indeterminate cytology; however, additional details may make initial total thyroidectomy (TT) preferable. We sought to identify patient-specific factors (PSFs) associated with initial TT in patients with indeterminate thyroid nodules. METHODS: Retrospective analysis of all patients with a thyroid nodule ≥ 1 cm and initial cytology of atypia of undetermined significance or suspicious for follicular neoplasm between 2012 and 2015 who underwent thyroidectomy. Medical records were reviewed for patient demographics, neck symptoms, nodule size, cytology, molecular test results, final histopathology, and additional PSFs influencing surgical management. Variables were analyzed to determine associations with the use of initial TT. Logistic regression analyses were performed to identify independent associations. RESULTS: Of 325 included patients, 182/325 (56.0%) had HT and 143/325 (44.0%) had TT. While patient age and sex, nodule size, and cytology result were not associated with initial treatment, five PSFs were associated with initial TT (p < 0.0001). These included contralateral nodules, hypothyroidism, fluorodeoxyglucose avidity on positron emission tomography scan, family history of thyroid cancer, and increased surgical risk. At least one PSF was present in 126/143 (88.1%) TT patients versus 47/182 (25.8%) HT patients (p < 0.0001). Multivariate logistic regression analysis demonstrated that these variables were the strongest independent predictor of TT (odds ratio 45.93, 95% confidence interval 18.80-112.23, p < 0.001). CONCLUSIONS: When surgical management of an indeterminate cytology thyroid nodule was performed, several PSFs were associated with a preference by surgeons and patients for initial TT, which may be useful to consider in making decisions on initial operative extent.

Antitumor effects of hyaluronan inhibition in desmoid tumors.

Desmoid tumors (DTs) are rare, mesenchymal tumors that exhibit features of an abundant wound healing process. Previously, we showed that mesenchymal stem cells (MSCs) are constituents of DTs and may contribute to desmoid tumorigenesis via activities associated with wound healing. Hyaluronan (HA) is a long-charged chain of repeating glucuronate and N-acetylglucosamine disaccharides that is synthesized by HA synthases (HAS) and degraded by hyaluronidases (HYAL). HA is secreted into the extracellular matrix by injured stroma and is important for normal tissue repair and neoplastic progression. Here, we investigated the presence of HA in DTs and the antitumor effects of the HA inhibitor, 4-methylumbelliferone (4-MU), on DT-derived mesenchymal cells. By immunohistochemistry and enzyme-linked immunosorbent assay, we found abundant expression of HA in 29/30 DTs as well as >5-fold increased HA levels in DT-derived cell lines relative to controls. Immunohistochemistry also demonstrated high expression of HAS2 in DTs, and quantitative PCR analysis showed increased HAS2 upregulation in frozen DTs and DT-derived cells. 4-MU treatment of DT-derived cells significantly decreased proliferation as well as HA and HAS2 levels. Fluorescent immunohistochemistry showed that MSCs in DTs coexpressed HA, HAS2, HYAL2, as well as the major HA receptor CD44 and HA coreceptor TLR4. Taken together, our results suggest that paracrine regulation of HA signaling in DTs may contribute to MSC recruitment and tumor proliferation. Future studies investigating the role of HA in tumor-stroma crosstalk and inhibition of HA-MSC interactions as a novel therapeutic target in DTs and other solid tumors are warranted.