Validated predictive model for treatment and prognosis of adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma has a poor prognosis and multiple clinical, pathological, and treatment variables. Currently, we lack a prognostic and treatment calculator to determine the survival and efficacy of adjuvant chemoradiation. We aimed to validate a calculator to assess prognosis and treatment. METHODS: We searched the National Cancer Database to identify patients with adrenocortical carcinoma surgically treated from 2004 to 2020 and randomly allocated them into a training (80%) or validation set (20%). We analyzed the variables of age; sex; Charlson Comorbidity Index; insurance status; tumor size; pathologic tumor, node, and metastasis categories; surgical margins; and use of chemotherapy and radiation therapy. We used Cox regression prediction models and bootstrap coefficients to generate a mathematical model to predict 5- and 10-year overall survival. After using the area under the curve analysis to assess the model's performance, we compared overall survival in the training and validation sets. RESULTS: Multivariable analysis of the 3,480 patients included in the study revealed that all variables were significant except sex (P < .05) and incorporated into a mathematical model. The area under the curve for 5- and 10-year overall survival was 0.68 and 0.70, respectively, for the training set and 0.70 and 0.72, respectively, for the validation set. For the bootstrap coefficients, the 5- and 10-year overall survival was 6.4% and 4.1%, respectively, above the observed mean. CONCLUSION: Our model predicts the overall survival of patients with adrenocortical carcinoma based on clinical, pathologic, and treatment variables and can assist in individualizing treatment.

Treatment Differences for Adrenocortical Carcinoma by Race and Insurance Status.

INTRODUCTION: To determine if treatment and clinical outcomes of adrenocortical carcinoma (ACC) vary by race and insurance status. METHODS: ACC patients from the National Cancer Database (2004-2017) were reviewed. Race was defined as White versus minority (Black and Hispanic). Insurance types were private (PI) versus other (Medicaid/uninsured/unknown). Metastatic ACC (M-ACC) was defined as distant metastases at the time of diagnosis; nonmetastatic ACC (NM-ACC) patient had no distant disease. RESULTS: Of 2351 NM-ACC patients, 83.6% were White and 16.4% minority. There were 1216 M-ACC patients, with 80.3% White and 19.8% minority. Both White NM-ACC and M-ACC patients had more PI (each P < 0.001). PI NM-ACC was associated with a shorter duration from diagnosis to first treatment (14 versus 18 d, P = 0.005). Both NM-ACC and M-ACC with PI were more likely to receive surgery (92.6% versus 86.9%, P = 0.001 and 35.4% versus 27%, P = 0.02) and to receive surgery sooner (13 versus 16 d, P = 0.03). M-ACC with PI were more likely to receive chemotherapy (63.6% versus 54.3%, P = 0.01) and to have lymph nodes examined (14.8% versus 8.6%, P = 0.02). Length of stay postoperatively was shorter for White NM-ACC (6 versus 7 d, P = 0.04) and M-ACC (8 versus 17 d, P = 0.02). For NM-ACC and M-ACC, the 30-d readmission, 90-d mortality, and overall survival were similar by race. A multivariable analysis showed minorities (OR 0.69, 95% confidence interval 0.54-0.88, P = 0.003) and patients without PI (OR 0.75, 95% confidence interval 0.58-0.97, P = 0.03) were less likely to have surgery. However, a multivariable analysis showed survival was similar for White versus minority patients and PI versus other. CONCLUSIONS: White NM-ACC or M-ACC and PI were more likely to receive surgery and timely multimodality care. These disparities were not associated with differences in 90-d mortality or overall survival.

Treatment differences at high volume centers and low volume centers in non-metastatic and metastatic adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is rare with poor survival. Do treatment and outcomes vary by volume? METHODS: NCDB (2004-2017) was searched for patients with ACC. High-volume centers (HVCs) were defined by ≥ 15 ACC and low-volume centers by ≤ 7 total cases. Multivariable Cox and logistic regression analysis were performed. RESULTS: ACC patients at HVCs were significantly more likely to have surgery, chemotherapy, and had lower 90-day readmission. HVCs were significantly more likely than LVCs to administer chemotherapy to surgical NonMetastatic (NM)-ACC patients. There was no significant difference in overall survival (OS), 90-day mortality, length of stay, or radiation treatments between the two. Operative Metastatic (M)-ACC at HVC had significantly improved OS, more chemotherapy administered, and lower 90-day mortality. CONCLUSION: NM-ACC and M-ACC treated at HVCs were more likely to have surgery and multimodality therapy. NM-ACC having surgery at HVCs and LVCs had similar OS. M-ACC at HVCs had improved OS and 90-day mortality.

Radioactive iodine does not improve overall survival for patients with aggressive variants of papillary thyroid carcinoma less than 2 cm.

BACKGROUND: Tall cell and diffuse sclerosing variants of papillary thyroid cancer are associated with aggressive features. Radioactive iodine after total thyroidectomy is poorly studied. METHODS: Patients ≥18 years in the National Cancer Data Base from 2004 to 2016 with classic papillary thyroid cancer, tall cell, or diffuse sclerosing 1 mm to 40 mm were identified. Logistic regression identified factors associated with aggressive features. Overall survival was assessed using Kaplan-Meier method and log-rank tests, after propensity score matching for clinicopathological and treatment variables. RESULTS: A total of 155,940 classic papillary thyroid cancer patients, 4,011 tall cell, and 507 diffuse sclerosing were identified. Tall cell patients represented an increasing proportion of the study population during the analysis period, whereas diffuse sclerosing and classic papillary thyroid cancer patients showed a statistically significant decline. Extrathyroidal extension and nodal involvement were more prevalent among tall cell and diffuse sclerosing patients when compared to those diagnosed with classic papillary thyroid cancer (P < .01). Adjuvant radioactive iodine was less frequently used in patients with classic papillary thyroid cancer when compared to tall cell and diffuse sclerosing patients (42.6% vs 62.4%, 59.0%; P < .001, respectively). Aggressive variants receiving total thyroidectomy versus total thyroidectomy + radioactive iodine propensity score matched across clinicopathologic variables were analyzed. There was no difference in overall survival between the 2 treatment groups for tumors <2 cm (01-1.0 cm, 92.2% vs 84.8%; P = .98); (1.0-2.0 cm, 72.7% vs 88.1%; P = .82). However, overall survival was improved for total thyroidectomy + radioactive iodine propensity score matched patients with tumor sizes 21 to 40 mm versus total thyroidectomy (83.4% vs 70.0%, P = .004). CONCLUSION: For aggressive tumor variants ≤2 cm treated with total thyroidectomy, there is no overall survival advantage provided by the addition of adjuvant radioactive iodine.

Overall survival is improved with total thyroidectomy and radiation for male patients and patients older than 55 with T2N0M0 Stage 1 classic papillary thyroid cancer.

BACKGROUND: We examine whether surgery extent and radiation administration affect overall survival for cT2N0M0 classic papillary thyroid cancer according to age and sex. METHODS: Patients with cT2N0M0 classic papillary thyroid cancer tumors in the National Cancer Data Base (2004-2016) were selected. Multivariable Cox regression analysis compared patients (combined male + female cohorts) having lobectomy to those having total thyroidectomy with or without radiation (primarily radioactive iodine) for ages: 18 to 45, 46 to 55, and >55 years. In addition, 1:1 propensity score matching and Kaplan-Meier curves with 10-year overall survival estimates, and log-rank test were stratified by age and sex. RESULTS: Lobectomy had equivalent overall survival to total thyroidectomy without and with radiation for patients (combined male + female cohorts) aged 18 to 45 and 46 to 55 years on multivariable analysis. On propensity score matching there was overall survival advantage for total thyroidectomy with radiation over both lobectomy and total thyroidectomy for men (ages 18-90+ combined) and overall survival advantage in patients (combined male + female cohort) aged >55 years having total thyroidectomy with radiation versus lobectomy. On propensity score matching there were no overall survival differences in women (ages 18-90+ combined) or patients (combined male + female cohort) aged 18 to 45 and 46 to 55 years having either lobectomy, total thyroidectomy, or total thyroidectomy with radiation. CONCLUSION: For cT2N0M0 classic papillary thyroid cancer, total thyroidectomy with radiation improves 10-year overall survival for patients (combined male + female cohort) aged >55 years and men (ages 18-90+ combined).

Radioactive iodine-125 seed localization as an aid in reoperative neck surgery.

BACKGROUND: Scarring and disrupted tissue planes add to already-complex neck anatomy and make localization of nonpalpable pathology difficult in cervical endocrine reoperations. We describe the use of radioactive iodine-125 seed localization (RSL) in 6 patients with metastatic papillary thyroid carcinoma (PTC) and 2 with recurrent hyperparathyroidism. METHODS: Eight patients had 2-D ultrasound-guided RSL of the target lesion, 0-3 days preoperatively. Intraoperative gamma probe (Neoprobe) was used to plan incision placement and localize the implanted seed. Recorded operative variables included: number of lymph nodes (LNs) harvested, estimated blood loss (EBL), operative time, length of stay (LOS) and RSL and operative complications. RESULTS: All patients had successful resection of the targeted area and removal of the radioactive seed. There was no seed migration. Two complications occurred in the thyroid group. CONCLUSION: Radioactive iodine 125 seeds facilitate successful localization of endocrine pathology during reoperative cervical procedures.

Extrathyroidal extension predicts negative clinical outcomes in papillary thyroid cancer.

BACKGROUND: The eighth edition American Joint Committee on Cancer tumor-node-metastasis staging for well-differentiated thyroid cancers, no longer considers "minimal" extrathyroidal extension for tumor staging. This change prompted us to examine the effect of extrathyroidal extension on patient outcomes. METHODS: Patients (n = 177,497) in the 2016 National Cancer Database with classic papillary thyroid cancer were evaluated to determine the effect of extrathyroidal extension on overall survival and risk for nodal and distant metastases. Kaplan-Meier curves with the log-rank test were used to evaluate survival differences. Multivariable Cox and logistic regression analyses included relevant clinicopathologic variables (e.g. age, sex, race, and Charlson Comorbidity Index). RESULTS: Patients with "minimal" extrathyroidal extension had worse survival versus patients with no extrathyroidal extension (10-year survival 89.3% vs 93.1%, hazard ratio 1.23; 95% confidence interval, 1.13-1.35; P < .001). Any extrathyroidal extension was associated with higher risks for lymph node (odds ratio 2.78; 95% confidence interval, 2.69-2.87) and distant metastasis (odds ratio 3.5; 95% confidence interval, 3.05-4.04). These associations persisted when comparing "micro" (extension into the thyroid capsule) versus none for nodal risk (odds ratio 1.25; 95% confidence interval, 1.18-1.33) and distant metastasis (OR 1.52; 95% confidence interval, 1.11-2.09). CONCLUSION: All levels of extrathyroidal extension, including microscopic, were associated with increased risk for nodal and distant metastasis. Both minimal and macroscopic extrathyroidal extension were also associated with decreased overall survival. Such findings have the potential to affect the clinical decision making for patients diagnosed with papillary thyroid cancer.

Virtual Surgical Fellowship Recruitment During COVID-19 and Its Implications for Resident/Fellow Recruitment in the Future.

BACKGROUND: The COVID-19 pandemic has overlapped with the scheduled interview periods of over 20 surgical subspecialty fellowships, including the Complex General Surgical Oncology (CGSO) fellowships in the National Resident Matching Program and the Society of Surgical Oncology's Breast Surgical Oncology fellowships. We outline the successful implementation of and processes behind a virtual interview day for CGSO fellowship recruitment after the start of the pandemic. METHODS: The virtual CGSO fellowship interview process at the University of Chicago Medicine and NorthShore University Health System was outlined and implemented. Separate voluntary, anonymous online secure feedback surveys were email distributed to interview applicants and faculty interviewers after the interview day concluded. RESULTS: Sixteen of 20 interview applicants (80.0%) and 12 of 13 faculty interviewers (92.3%) completed their respective feedback surveys. Seventy-five percent (12/16) of applicants and all faculty respondents (12/12) stated the interview process was 'very seamless' or 'seamless'. Applicants and faculty highlighted decreased cost, time savings, and increased efficiency as some of the benefits to virtual interviewing. CONCLUSIONS: Current circumstances related to the COVID-19 pandemic require fellowship programs to adapt and conduct virtual interviews. Our report describes the successful implementation of a virtual interview process. This report describes the technical steps and pitfalls of organizing such an interview and provides insights into the experience of the interviewer and interviewee.

Trends in nonoperative management of papillary thyroid microcarcinoma.

BACKGROUND: In 2010, a Japanese trial of nonoperative management for papillary thyroid microcarcinomas (PTmC) was published. This study determines if the prevalence of nonoperative management in the United States has changed and if there are predictors of this approach. METHODS: Patients treated for PTmC between 2004 and 2015 in the National Cancer Data Base were identified. Inclusion criteria were: classic or follicular variant papillary cancer histology, tumor size 1 to 10 mm, cN0 disease and no extrathyroidal extension or metastatic disease. Nonoperative management was assessed over time and compared between 2004-2010 and 2010-2015. Logistic regression identified factors associated with nonoperative management. RESULTS: Of 65 381 PTmC patients, 344 (0.5%) were treated nonoperatively. The annual rate of nonoperative management was similar at 0.6% in 2004 to 0.4% in 2010 (P = .755) but increased to 0.9% in 2015 (P < .001). There was no difference in patient age, race, comorbidities, or reason for nonoperative management between the two periods. Academic centers managed more patients nonoperatively. Multivariable logistic regression suggests older age, facility type, location, Hispanic, Asian, and Native American ethnicity were associated with nonoperative management. CONCLUSION: The vast majority of PTmC in the United States is treated with an operation. A small but significant increase in nonoperative management occurred between 2004-2010 and 2010-2015.

Increasing trend of bilateral neck exploration in primary hyperparathyroidism.

BACKGROUND: Bilateral neck exploration was the standard operation for primary hyperparathyroidism. With improvements in preoperative localization and use of intraoperative PTH (ioPTH) monitoring, minimally invasive unilateral neck exploration has been widely adopted. This study evaluates the trend in parathyroidectomies for primary hyperparathyroidism. METHODS: Parathyroidectomy for sporadic primary hyperparathyroidism was analyzed from 2010 to 2017. Exclusion criteria included previous neck surgery and concomitant procedures. The operations were classified as unilateral exploration (UE), UE converted to bilateral exploration (BE), or BE. Variables included preoperative and intraoperative factors. Outcomes included persistence, recurrence, permanent hypocalcemia and recurrent laryngeal nerve (RLN) injury. RESULTS: Four hundred thirty-one patients were reviewed. Since 2010, the rate of BE has increased from 30% to 50%. Disease duration, presence of bone disease, negative localization, baseline ioPTH <100, and ≥2 abnormal glands have increased. Mean operative time has not changed over time. Two percent of patients had persistent disease, <1% had recurrent disease, and 2% have had reoperation. Nine percent had temporary hypoparathyroidism, and 15 patients had temporary RLN injury. CONCLUSIONS: This study shows an increasing trend in BE for primary hyperparathyroidism. This increase was associated with lower baseline intraoperative parathyroid hormone (ioPTH) levels and smaller gland size. The operative approach for parathyroidectomy should be individualized and surgeons should not hesitate to perform BE when needed.

Aggressive variants of papillary thyroid microcarcinoma are associated with high-risk features, but not decreased survival.

BACKGROUND: This study compares pathologic features and overall survival of classic versus aggressive variants of papillary thyroid microcarcinoma (PMTC). METHODS: Patients ≥18 years in the National Cancer Data Base (2004-2015) with the subtypes of classic (cPTMC), tall cell (mTCV), or diffuse sclerosing (mDSV) PTC (≤1 cm) were identified. Overall survival was analyzed by Kaplan-Meier and propensity matched for clinicopathologic and treatment variables. RESULTS: There were 82,056 cPTMC patients, 923 mTCV, and 219 mDSV. Extrathyroidal extension and nodal involvement were more frequent in mTCV and mDSV versus cPTMC (P < .01). mTCV had more distant metastases than cPTMC (P = .02). On multivariable analysis, mTCV (odds ratio 4.19 [3.58-4.92], P < .001) and mDSV (odds ratio 2.76 [1.92-3.97]; P < .01) histologies were predictors of extrathyroidal extension. mTCV was an independent predictor of nodal metastases (odds ratio 1.51 [1.25-1.83], P < .01). Total thyroidectomy and radioactive iodine treatment were more commonly used in mTCV and mDSV patients when compared with cPTMC patients. Despite more aggressive features and more aggressive treatment in mTCV and mDSV patients, there was no difference in overall survival when compared with propensity-matched cPTMC patients. CONCLUSION: Although mTCV and mDSV have more aggressive pathologic features and were treated more aggressively, there were no differences in overall survival compared with propensity-matched cPTMC patients.

Parathyroidectomy is Safe in Elderly Patients: A National Surgical Quality Improvement Program Study.

BACKGROUND: With increasing age, the incidence of hyperparathyroidism is increased. This study evaluates parathyroidectomy outcomes in elderly patients. METHODS: Primary hyperparathyroidism patients having parathyroidectomy as listed in the 2005-2017 ACS-NSQIP database were separated by age: ≤60, 61-79 and ≥80. Outcomes included complications, 30-day mortality, return to the OR, operating times, and hospital length of stay (LOS). Multivariable logistic regression was used to compare patients 61-79 and ≥80 to those ≤60. Patients ≤60 and ≥80 were propensity score matched using gender, race, BMI, smoking status, steroid use, modified frailty index (mFI), ASA class, procedure, setting, anesthesia, and wound class. Morbidity and mortality were compared to ACS-NSQIP database patients having elective inguinal hernia repair. RESULTS: Of 47,701 patients: 22,220 were ≤60, 22,683 were 61-79, and 2798 were ≥80. Patients ≥80 had more complications (2.3% vs. 1.5% for 61-79 and 1.0% for ≤60, p < 0.01), LOS > 1 day (10.3% vs. 5.8% and 6.7%, p < 0.01), and mortality (0.21% vs. 0.11% and 0.03%, p < 0.01). On multivariable analysis of the overall population, older age, male gender, steroid use, high mFI, outpatient procedure, and general anesthesia increased the risk of complications. On propensity score matched analysis, there was no difference in complications (1.5% vs. 2.2%, p = 0.06) or mortality (0.04% vs. 0.23%, p = 0.12) between patients ≤60 and ≥80. Parathyroidectomy morbidity and mortality was lower than that for elective inguinal hernia repair in patients ≥80 (2.3% vs. 10% and 0.21% vs. 1.1%, p < 0.01). CONCLUSIONS: Parathyroidectomy is a safe operation, offering lower morbidity and mortality than elective hernia repair in all age groups including octogenarians.

Survival with Follicular and Hurthle Cell Microcarcinoma Compared to Papillary Thyroid Microcarcinoma: A Population Study of 84,532 Patients.

BACKGROUND: This study compares survival in patients with the rare subtypes of follicular (FTmC) and Hurthle cell (HCmC) microcarcinoma compared to that of papillary thyroid (PTmC) microcarcinoma. METHODS: Patients with FTmC and HCmC were selected from the National Cancer Database 2004-2015 and compared with PTmC. Patient clinicopathological characteristics and overall survival (OS) were analyzed. Multivariable logistic and Cox regression analysis evaluated binary outcomes and predictors of survival. A propensity score matched analysis using age, gender, race, extrathyroidal extension (ETE), nodal status, distant metastasis, radiation, and operation was performed to evaluate the difference in OS with FTmC, HCmC, and PTmC. RESULTS: We identified 858 FTmC, 476 HCmC, and 82,056 PTmC. FTmC was less likely to have macroscopic ETE compared to PTmC (2.6% vs. 3.1% p = 0.03), but more likely to have distant metastasis (2.3% vs. 0.2%, p < 0.01). FTmC and HCmC were less likely to have nodal metastasis (2.7%, 2.5% vs. 10.9%, p < 0.01). Ten-year OS was decreased in patients with FTmC (91.4%, p = 0.04) and HCmC (89.8%, p < 0.01) compared to PTmC (93.5%). On multivariable analysis, histology was not associated with OS. With HCmC, older age (OR 1.13, p < 0.01) and male gender (OR 2.72, p = 0.03) were associated with decreased OS. In propensity matched analysis, there was no difference in 10-year OS with FTmC and PTmC (91.4% vs. 93.7%, p = 0.54), but HCmC had decreased OS compared to PTmC (89.8% vs. 94.3%, p = 0.04). CONCLUSIONS: Patients with FTmC have comparable OS to those with PTmC, but HCmC has decreased OS especially in older and male patients.

Thyroid Lobectomy for T1b-T2 Papillary Thyroid Cancer with High-Risk Features.

BACKGROUND: Thyroid lobectomy (TL) has been proposed as definitive surgical treatment for papillary thyroid cancers (PTC) up to 4 cm. This study evaluates the use and appropriateness of TL for T1b and T2 PTC. STUDY DESIGN: The National Cancer Database was interrogated for adult patients having TL for T1b-T2 PTC between 2004 and 2014. Patients who should have undergone total thyroidectomy (TT) instead of lobectomy based on high-risk tumor features were identified. The 2 groups were compared for clinical and demographic characteristics, and overall survival. RESULTS: Of 8,083 patients undergoing lobectomy, 1,552 patients had high-risk features and should have undergone TT. These included 194 with cN1, 571 with pN1, 307 with lymphovascular invasion (LVI), 645 with extra thyroidal extension (ETE), 567 with positive margins, 42 with poorly differentiated PTC, and 25 with M1 disease. At 10 years of follow-up, 92.4% of appropriate lobectomy (aTL) patients were alive compared with 88.5% of inappropriate lobectomy (iTL) patients (p < 0.001). On univariate and multivariable Cox survival analysis, age greater than 45 years, male sex, comorbidities, government or no insurance, low income, and tumor size >2 cm were associated with poorer survival (all p < 0.05). Thyroid lobectomy patients with high-risk features had significantly higher mortality on unadjusted (hazard ratio [HR] 1.98, 95% CI 1.52 to 2.59, p < 0.001) and adjusted survival analysis (HR 1.97, 95% CI 1.51 to 2.58, p < 0.001). Total thyroidectomy with radioiodine treatment had improved overall survival in comparison to iTL (HR 0.65, 95% CI 0.51 to 0.83, p < 0.001). CONCLUSIONS: A substantial number of patients (19.2%) with tumor size >1 cm and high-risk features undergo thyroid lobectomy for PTC. Exclusion of high-risk features is important when adopting lobectomy as the definitive surgical therapy for T1b and T2 PTC because they have a potential adverse effect on long-term survival.

Are we Overtreating Hormone Receptor Positive Breast Cancer with Neoadjuvant Chemotherapy? Role of OncotypeDx® for Hormone Receptor Positive Patients Undergoing Neoadjuvant Chemotherapy.

BACKGROUND: The utilization of OncotypeDx in the setting of neoadjuvant chemotherapy (NCT) is not well defined. The objective of this study was to determine what proportion of hormone receptor (HR)-positive patients undergoing NCT would not benefit from chemotherapy based on OncotypeDx recurrence scores (RS) and predictors of a high RS as defined by the TAILORx trial. METHODS: The National Cancer Data Base was used to identify patients with unilateral clinical stage I-III HR+/Her2- breast cancer who had an OncotypeDx score and who had undergone NCT. Patients undergoing adjuvant chemotherapy were used as a comparison group. RESULTS: Of 307,666 patients, 41.8% had testing with OncotypeDx. Of these, 76.6% had no chemotherapy, 22.3% adjuvant chemotherapy, and 1.1% NCT. OncotypeDx testing in NCT patients increased from 4.9% in 2010 to 8.2% in 2015. Of NCT patients with OncotypeDx testing, 11.6% had RS < 11, 44.4% RS 11-25, and 43.9% RS > 25. In patients age ≤ 50 years, 14.5% had RS < 11, 12.4% RS 11-15, 31.4% RS 16-25, and 41.7% RS > 25. Predictors of RS > 25 on multivariable analysis included grade 3 tumors (odds ratio [OR] 3.83) and PR-negative tumors (OR 5.26) but not clinical T or N stage (p > 0.05). CONCLUSIONS: More than half of patients with OncotypeDx testing are being overtreated with NCT, and a third of younger patients are being overtreated. Predictors of a high RS are reliably available at core biopsy, suggesting an application of OncotypeDx in determining the need for NCT for some HR-positive breast cancers.

Impact of the Society of Surgical Oncology-American Society for Radiation Oncology Margin Guidelines on Breast-Conserving Surgery and Mastectomy Trends.

BACKGROUND: In 2014, the Society of Surgical Oncology and American Society for Radiation Oncology guidelines defined negative margin for stage I and II breast cancer as "no tumor on ink." We hypothesized that repeat operation rates have decreased since the guideline introduction and would be associated with changes in overall surgical trends. STUDY DESIGN: The National Cancer Database was used to identify women who underwent initial breast-conserving surgery (BCS) for stage I and II breast cancer from 2004 to 2015. RESULTS: Of 521,578 patients that underwent initial BCS, 82.7% had BCS alone and 17.3% had repeat operation: 67% with BCS followed by another BCS, 24% with BCS followed by unilateral mastectomy, and 9% with BCS followed by bilateral mastectomy (BM). The repeat operation rate decreased from 16.2% in 2004 to 14.0% in 2015 (p < 0.01). Breast-conserving surgery with repeat BCS decreased from 12.8% to 9.7%, and BCS followed by BM increased from 0.7% in 2004 to 1.9% 2013, then decreased to 1.4% in 2015. Trends for all surgical patients regardless of initial procedure showed a BCS rate of 64.0% in 2013 that increased to 67.6% in 2015. The BM rate increased from 4.6% in 2004 to 13.6% in 2013, then decreased to 12.8% in 2015 (p < 0.05). Adjusted multivariable regression found independent predictors of repeat operation to be diagnosis before 2014 (odds ratio [OR] 1.25), age younger than 50 years (OR 1.70), Her2neu receptor-positive tumors (OR 1.61), and lobular histology (OR 1.61). CONCLUSIONS: Repeat operation rates are decreasing after 2014, which is also associated with a rise in BCS and decrease in BM rates. Dissemination of margin guidelines for early-stage breast cancer might be impacting overall surgical trends.

Degree of hypercalcemia correlates with parathyroidectomy but not with symptoms.

BACKGROUND: Primary hyperparathyroidism (HPT) is an undertreated disease. This study's purpose is to determine if the calcium levels correlate with prevalence of symptoms and surgical treatment in patients with primary HPT. METHOD: Patients treated in 2006-2015 with serum calcium≥10.0 mg/dL and PTH>65 pg/mL were identified and stratified based on calcium level: 10.0-10.3 (normocalcemia), 10.4-11.2 (moderate), and ≥11.3 (severe) mg/dL. Clinical variables and rates of surgery were compared between the three groups. RESULTS: A total of 2266 patients were identified: 303 with normocalcemia, 1513 with moderate hypercalcemia, and 450 with severe hypercalcemia. All three groups had similar rates of nephrolithiasis (p = 0.10), osteoporosis (p = 0.82), and reduced GFR (p = 0.06). Most patients (85%) had at least one surgical indication, but only 29% underwent parathyroidectomy. Higher calcium levels were correlated with higher surgical rates: 12% for Ca 10.0-10.3, 27% for Ca 10.4-11.2, and 46% for Ca≥11.3 (p < 0.01). CONCLUSION: Prevalence of symptoms does not correlate with calcium levels. Patients with normocalcemia and moderate hypercalcemia were equally likely to have a surgical indication, but normocalcemic patients are less likely to receive surgery.

Epigenetic chromatin conformation changes in peripheral blood can detect thyroid cancer.

BACKGROUND: Fine needle aspiration has been the traditional method for diagnosing thyroid cancer. Epigenetic chromatin conformation changes offer an alternative method of diagnosing cancer. The purpose of this study is to evaluate an EpiSwitch assay of epigenetic markers that can be used to diagnose thyroid cancer in blood samples. METHODS: From 2014 to 2016, adult patients with thyroid nodules having thyroidectomy were recruited and grouped based on benign, malignant, and atypia of undetermined significance or follicular lesions of undetermined significance fine needle aspiration cytology. Blood samples were collected before surgery. Final pathologic diagnosis was made from the thyroid specimens. Patients' blood samples were analyzed using the EpiSwitch assay, (Oxford Biodynamics, Oxford, UK), and the results were compared with surgical pathology to determine assay performance. RESULTS: In total, 58 patients were recruited: 20 benign, 20 malignant, and 18 atypia or follicular lesions of undetermined significance. An analysis of the malignant and benign fine needle aspiration groups found 6 epigenetic markers for thyroid. A total of 28 (48%) patients had thyroid cancer. The assay was able to correctly identify 25 of the 28 malignant nodules, showing sensitivity of 89.3% and specificity of 66.7%. The positive predictive value for the assay was 71.4%, whereas the negative predictive value was 87.0%. CONCLUSION: An epigenetic assay of peripheral blood shows high sensitivity in detecting thyroid cancer and provides an additional method for its diagnosis.

Differences in the Impact of Age on Mortality in Well-Differentiated Thyroid Cancer.

INTRODUCTION: Well-differentiated thyroid cancer (WDTC) is unique in that patient age is part of staging. Several studies have shown a need to increase the age threshold in staging for WDTC, but the separate impact of age on prognosis for papillary and follicular carcinomas has not been examined. We hypothesize that age impacts survival differently for papillary and follicular carcinomas. METHODS: Patients with invasive papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) between 2004 and 2013 were identified in the National Cancer Database, and were stratified by histologic type. Overall survival (OS) was analyzed using multivariable Cox regression, and the Youden index was used to find the optimal age threshold for both histologies. RESULTS: A total of 204,139 patients with WDTC were identified. Ninety-two percent had PTC, while 7.7% had FTC. The average age was 48.4 years and OS was 96.3%, with a median follow-up of 52.7 months. When analyzing age in 5-year increments, 10-year mortality increased incrementally by 30-50% per age group for PTC, from age < 35 to ≥ 70 years, without an obvious inflection point. However, FTC patients experienced a more than threefold increase in 10-year mortality from age 40-44 years (2.5%) to age 45-49 years (7.9%). The same pattern was found on multivariable Cox regression. The Youden index found the optimal age thresholds were 58.5 years for PTC and 46.2 years for FTC. CONCLUSION: OS for PTC decreases incrementally with age, but OS for FTC decreases significantly in patients aged 45 years and older. A higher age threshold may inappropriately downstage some high-risk follicular cancer patients.