Circulating MicroRNA as a Potential Biomarker for Skeletal Disease in Primary Hyperparathyroidism: A Case-control Study.

OBJECTIVE: The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with Primary hyperparathyroidism (PHPT) and identify miRNA biomarkers of bone homeostasis. BACKGROUND: PHPT is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. METHODS: We performed a prospective case-control study of postmenopausal females with PHPT and control subjects matched for race, age, and bone mineral density (BMD). We collected clinical and biochemical data, assessed BMD by dual-energy x-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers, and BMD. RESULTS: A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, 9 (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a-3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a, and miR-19b-3p) were differentially expressed in PHPT compared with matched control subjects. All 9 differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and 8 of the 9 correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these 9 miRNAs on principle component analysis. CONCLUSIONS: These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA.

Defining Optimal Management of Non-metastatic Adrenocortical Carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive, deadly malignancy. Resection remains the primary treatment; however, there is conflicting evidence regarding the optimal approach to and extent of surgery and the role of adjuvant therapy. We evaluated the impact of surgical technique and adjuvant therapies on survival in non-metastatic ACC. METHODS: We performed a retrospective cohort study of subjects who underwent surgery for non-metastatic ACC between 2010 and 2019 utilizing the National Cancer Database. The primary outcome was overall survival. Cox proportional hazards models were developed to identify associations between clinical and treatment characteristics and survival. RESULTS: Overall, 1175 subjects were included. Their mean age was 54 ± 15 years, and 62% of patients were female. 67% of procedures were performed via the open approach, 22% involved multi-organ resection, and 26% included lymphadenectomy. Median survival was 77.1 months. Age (hazard ratio [HR] 1.019; p < 0.001), advanced stage (stage III HR 2.421; p < 0.001), laparoscopic approach (HR 1.329; p = 0.010), and positive margins (HR 1.587; p < 0.001) were negatively associated with survival, while extent of resection (HR 1.189; p = 0.140) and lymphadenectomy (HR 1.039; p = 0.759) had no association. Stratified by stage, laparoscopic resection was only associated with worse survival in stage III disease (HR 1.548; p = 0.007). Chemoradiation was only associated with improved survival in patients with positive resection margins (HR 0.475; p = 0.004). CONCLUSION: Tumor biology and surgical margins are the primary determinants of survival in non-metastatic ACC. Surgical extent and lymphadenectomy are not associated with overall survival. In advanced disease, the open approach is associated with improved survival.

Modern Trends for Primary Hyperparathyroidism: Intervening on Less Biochemically Severe Disease.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is defined by autonomous parathyroid hormone secretion, which has broad physiologic effects. Parathyroidectomy is the only cure and is recommended for patients demonstrating symptomatic disease and/or end organ damage. However, there may be a benefit to intervening before the development of complications. We sought to characterize institutional trends in the biochemical and symptomatic presentation of PHPT and the associated cure and complication rates. METHODS: We performed a retrospective cohort study of 1087 patients undergoing parathyroidectomy for PHPT, evaluating patients at 2-year intervals between 2002 and 2019. We identified signs and symptoms of PHPT based on the 2016 American Association of Endocrine Surgery Guidelines. Trends were evaluated with Kruskal Wallis, Chi-square tests, and Fisher's exact tests. RESULTS: Patients with PHPT are presenting with lower parathyroid hormone (P = 0.0001) and calcium (P = 0.001) in the current era. Parathyroidectomy is more commonly performed for borderline guideline concordant patients with osteopenia (40.2%) and modest calciuria (median 246 mg/dL/24 h). 93.7% are cured, with no difference over time or between groups by guideline concordance. CONCLUSIONS: Parathyroidectomy is increasingly performed for patients who demonstrate modest bone and renal dysfunction. Patients experience excellent cure rates and rarely experience postoperative hypocalcemia, suggesting a role for broader surgical indications.

Adrenal Vein Sampling Results and Surgical Outcomes in Patients with Nonsuppressed Plasma Renin Activity.

PURPOSE: To determine adrenal vein sampling (AVS) and postadrenalectomy outcomes in patients with a nonsuppressed plasma renin activity (PRA) and elevated aldosterone-to-renin ratio (ARR). MATERIALS AND METHODS: The study sample included 23 patients with an ARR of >20 and PRA of >1 ng/mL/h (nonsuppressed group) and 69 patients with an ARR of >20 and PRA of <0.6 ng/mL/h (suppressed group) who underwent AVS from 2006 to 2023. Data regarding baseline clinical characteristics, AVS results, and outcomes after adrenalectomy were analyzed. RESULTS: The proportion of patients in the nonsuppressed group who had a lateralization index of >4 was lower than that in the suppressed group, although this was nonsignificant (43% vs 62%; P = .15). The mean lateralization index in the nonsuppressed group was lower compared with that in the suppressed group (8.7 vs 17.4; P = .05). The proportion of patients in the nonsuppressed group with improved or cured hypertension following adrenalectomy was similar to that of patients in the suppressed group who also underwent surgery (6/8, 75%, vs 25/32, 78%; P = .71). All hypokalemic patients (32/32) who underwent adrenalectomy had normalization of their potassium levels following procedure. CONCLUSIONS: Nearly half of patients with nonsuppressed PRA lateralized with AVS. The patients who did lateralize had similar blood pressure response and correction of hypokalemia following adrenalectomy, regardless of PRA. Therefore, patients with a nonsuppressed PRA (>1 ng/mL/h) should still be considered for AVS provided the ARR is elevated.

Surgical Management of Metastatic Adrenocortical Carcinoma.

Introduction: Adrenocortical carcinoma (ACC) is a notoriously aggressive cancer with a dismal prognosis, especially for patients with metastatic disease. Metastatic ACC is classically a contraindication to operative management. Here, we evaluate the impact of primary tumor resection and metastasectomy on survival in metastatic ACC. Methods: We performed a retrospective cohort study of patients with metastatic ACC (2010-2019) utilizing the National Cancer Database. The primary outcome was overall survival (OS). Cox proportional hazards models were developed to evaluate the associations between surgical management and survival. Propensity score matching (PSM) was utilized to account for selection bias in receipt of surgery. Results: Of 976 subjects with metastatic ACC, 38% underwent surgical management. Median OS across all patients was 7.6 months. On multivariable Cox proportional hazards regression, primary tumor resection alone (HR: 0.523; p<0.001) and primary resection with metastasectomy (HR: 0.372; p<0.001) were significantly associated with improved OS. Metastasectomy alone had no association with OS (HR: 0.909; p=0.740). Primary resection with metastasectomy was associated with improved OS over resection of the primary tumor alone (HR: 0.636; p=0.018). After PSM, resection of the primary tumor alone remained associated with improved OS (HR 0.593; p<0.001), and metastasectomy alone had no survival benefit (HR 0.709; p=0.196) compared with non-operative management; combined resection was associated with improved OS over primary tumor resection alone (HR 0.575, p=0.008). Conclusion: In metastatic ACC, patients may benefit from primary tumor resection alone or in combination with metastasectomy, however further research is required to facilitate appropriate patient selection.

Assessing the Frequency of Deferrable Thyroid Nodule Biopsies to De-escalate Low-Value Care.

OBJECTIVE: Thyroid nodules are common, yet fewer than 1 in 10 harbors malignancy. When present, thyroid cancer is typically indolent with excellent survival. Therefore, patients who are not candidates for thyroid cancer treatment due to comorbid disease may not require further thyroid nodule evaluation. The goal of this study was to determine the rate of deferrable thyroid nodule biopsies in patients with limited life expectancy. METHODS: We identified patients who underwent thyroid fine needle aspiration (FNA) between 2015 and 2018 at our institution. The primary outcome was the number of deferrable FNAs, defined as FNAs performed in patients who died within 2 years after biopsy. Secondary outcomes included cytologic Bethesda score, procedure costs, and final diagnosis on surgical pathology. Multivariable logistic and Cox proportional hazards regressions were used to evaluate factors associated with FNA in patients with limited life expectancy. RESULTS: A total of 2565 FNAs were performed. Most patients were female (79%), and 37 (1.5%) patients died within 2 years. Nonthyroid specialists were significantly more likely to order deferrable FNAs (odds ratio 4.13, P < .001). Of the patients who died within 2 years, most (78%) had a concomitant diagnosis of nonthyroid cancer, and 4 went on to have thyroid surgery (Bethesda scores: 3, 4, 4, and 6). Spending associated with deferrable FNAs and subsequent surgery totaled over $98 000. CONCLUSIONS: Overall, the rate of deferrable thyroid nodule biopsies was low. However, there is an opportunity to reduce low-value biopsies in patients with a concurrent nonthyroid cancer by partnering with oncology providers.

Adrenal Metastasectomy in the Era of Immuno- and Targeted Therapy.

Adrenal metastasectomy has an increasing role in multimodality oncologic care for diverse primary cancer types. In this review, we discuss the epidemiology, evaluation, and contemporary best practices in the management of adrenal metastases from various primaries. Initial evaluation of suspected adrenal metastases should include diagnostic imaging to assess the extent of tumor involvement and determine surgical resectability, as well as biochemical evaluation for hormone secretion. Biopsy has a minimal role and should only be performed in tumors that are established to be non-hormone secreting and when the biopsy results would change clinical management. Adrenal metastasectomy is associated with survival benefit in selected patients. We suggest that adrenal metastasectomy has the greatest benefit in four clinical scenarios: (1) disease limited to the adrenal gland in which adrenalectomy renders the patient disease-free; (2) isolated progression in the adrenal gland in the setting of otherwise controlled metastatic extra-adrenal disease; (3) need for palliation of symptoms related to adrenal metastases; or (4) in the context of tissue-based clinical trials. Both minimally invasive and open adrenalectomy techniques are safe and appear to have equivalent oncologic outcomes. Minimally invasive approaches are favored when technically feasible while maintaining oncologic principles. A multidisciplinary evaluation including clinicians with expertise in the primary cancer type is essential to the successful management of adrenal metastases.

Primary Hyperparathyroidism in Young Adult Patients.

BACKGROUND: Primary hyperparathyroidism (PHPT) affects 2% of Americans over 55 years of age, and is less common in younger patients. Pediatric PHPT patients have higher rates of multigland disease (MGD). We studied young adult patients to determine whether they have similarly elevated rates of MGD and would benefit from routine bilateral neck exploration. METHODS: Retrospective chart review was performed on patients who underwent parathyroidectomy for PHPT (2000-2019). Cohorts were defined by age: Group A (18-40 years) and Group B (> 40 years). Univariate and multivariate logistic regression analyses were performed. RESULTS: Of 3889 patients with PHPT, 9.1% (n = 352) were included in Group A. On multivariate analysis, multiple endocrine neoplasia (odds ratio [OR] 6.3, 95% confidence interval [CI] 3.1-12.7), male sex (OR 1.3, 95% CI 1.0-1.5), family history of PHPT (OR 2.7, 95% CI 1.6-4.8), prior parathyroidectomy (OR 2.2, 95% CI 1.6-3.0), and non-localizing imaging (OR 1.8, 95% CI 1.5-2.1) were associated with MGD; younger age was not an independent risk factor. In patients with sporadic PHPT (n = 3833), family history was most strongly associated with MGD (OR 4.0, 95% CI 2.2-7.3). CONCLUSIONS: In our population of patients with sporadic PHPT, a positive family history of PHPT was strongly associated with MGD; additional associations were found with prior parathyroidectomy, non-localizing imaging, and male sex. Younger age was not an independent risk factor. Age alone in the absence of a family history should not raise suspicion for MGD nor determine the need for bilateral neck exploration.

Disparities in Presentation, Treatment, and Survival in Anaplastic Thyroid Cancer.

BACKGROUND: Disparities have been previously described in the presentation, management, and outcomes of other thyroid cancer subtypes; however, it is unclear whether such disparities exist in anaplastic thyroid cancer (ATC). METHODS: We identified patients with ATC from the National Cancer Database (2004-2020). The primary outcomes were receipt of surgery, chemotherapy, and radiation. The secondary outcome was 1-year survival. Multivariable logistic and Cox proportional hazards regressions were used to assess the associations between sex, race/ethnicity, and the outcomes. RESULTS: Among 5359 patients included, 58% were female, and 80% were non-Hispanic white. Median tumor size was larger in males than females (6.5 vs. 6.0 cm; p < 0.001) and in patients with minority race/ethnicity than in white patients (6.5 vs. 6.0 cm; p < 0.001). After controlling for tumor size and metastatic disease, female patients were more likely to undergo surgical resection (odds ratio [OR]: 1.20; p = 0.016) but less likely to undergo chemotherapy (OR: 0.72; p < 0.001) and radiation (OR: 0.76; p < 0.001) compared with males. Additionally, patients from minority racial/ethnic backgrounds were less likely to undergo chemotherapy (OR: 0.69; p < 0.001) and radiation (OR: 0.71; p < 0.001) than white patients. Overall, unadjusted, 1-year survival was 23%, with differences in treatment receipt accounting for small but significant differences in survival between groups. CONCLUSIONS: There are disparities in the presentation and treatment of ATC by sex and race/ethnicity that likely reflect differences in access to care as well as patient and provider preferences. While survival is similarly poor across groups, the changing landscape of treatments for ATC warrants efforts to address the potential for exacerbation of disparities.

Racial and Ethnic Disparities in Appropriate Thyroid Cancer Treatment, Before and After the Release of the 2015 American Thyroid Association Guidelines.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines reduced the recommended extent of therapy for low-risk thyroid cancers. Little is known about the impact of these changes on overall treatment patterns and on previously described racial/ethnic disparities in guideline-concordant care. This study aimed to assess trends in thyroid cancer care before and after release of the 2015 guidelines, with particular attention to racial/ethnic disparities. METHODS: Patients with well-differentiated thyroid cancer were identified from the National Cancer Database (2010-2018). An interrupted time series design was used to assess trends in treatment before and after the 2015 guidelines. Appropriateness of surgical and radioactive iodine (RAI) treatment was determined based on the ATA guidelines, and the likelihood of receiving guideline-concordant treatment was compared between racial/ethnic groups. RESULTS: The study identified 309,367 patients (White 74%, Black 8%, Hispanic 9%, Asian 6%). Between 2010 and 2015, the adjusted probability of appropriate surgery was lower for Black (- 2.1%; p < 0.001), Hispanic (- 1.0%; p < 0.001), and Asian (- 2.1%; p < 0.001) patients than for White patients. After 2015, only Hispanic patients had a lower probability of undergoing appropriate surgical therapy (- 2.6%; p = 0.040). Similarly, between 2010 and 2015, the adjusted probability of receiving appropriate RAI therapy was lower for the Hispanic (- 3.6%; p < 0.001) and Asian (- 2.4%; p < 0.001) patients than for White patients. After 2015, the probability of appropriate RAI therapy did not differ between groups. CONCLUSIONS: Between 2010 and 2015, patients from racial/ethnic minority backgrounds were less likely than White patients to receive appropriate surgical and RAI therapy for thyroid cancer. After the 2015 guidelines, racial/ethnic disparities in treatment improved.

Current Patterns of Treatment and Outcomes in Advanced Melanoma at a Single Institution.

INTRODUCTION: Treatment of advanced melanoma has been transformed by novel systemic therapies. The purpose of this study is to describe the current utilization patterns of immunotherapies with respect to survival outcomes in advanced melanoma. METHODS: We performed a retrospective cohort study of patients with Stage 3 and 4 melanoma at our institution (2009-2019). Primary outcomes included overall survival (OS) and progression free survival (PFS). Kaplan-Meier survival analysis and Cox proportional hazards regression analysis evaluated associations between covariates and survival outcomes. RESULTS: Of 244 patients, 5-y OS was 62.4%. Lymphovascular invasion (hazard ratio [HR] = 2.462, P = 0.030) was associated with shorter PFS whereas female gender (HR = 0.324, P = 0.010) was associated with longer PFS. Residual tumor (HR = 146, P = 0.006) and Stage 4 disease (HR = 3.349, P = 0.011) were associated with shorter OS. Use of immunotherapy increased from 2% to 23% over the study period, and use of neoadjuvant immunotherapy also increased up to 2016. Timing of immunotherapy administration was not significantly associated with survival. Of the 193 patients who received 2 or more treatment types, the most common treatment sequence was surgery followed by immunotherapy (n = 117, 60.6%). CONCLUSIONS: Immunotherapy is increasingly used for treatment of advanced melanoma. In this heterogeneous cohort, there was no significant association between timing of immunotherapy and survival outcomes.

Insurance-Based Disparities in Guideline-Concordant Thyroid Cancer Care in the Era of De-escalation.

INTRODUCTION: Prior studies have demonstrated insurance-based disparities in the treatment of well-differentiated thyroid cancer. However, it remains unclear whether these disparities have persisted in the era of the 2015 American Thyroid Association (ATA) management guidelines. The goal of this study was to assess whether insurance type is associated with the receipt of guideline-concordant and timely thyroid cancer treatment in a modern cohort. METHODS: Patients diagnosed with well-differentiated thyroid cancer between 2016 and 2019 were identified from the National Cancer Database. Appropriateness of surgical and radioactive iodine treatment (RAI) was determined based on the 2015 ATA guidelines. Multivariable logistic regression and Cox proportional hazard regression analyses, stratified at age 65, were used to evaluate the associations between insurance type and appropriateness and timeliness of the treatment. RESULTS: 125,827 patients were included (private = 71%, Medicare = 19%, Medicaid = 10%). Compared to privately insured patients, patients with Medicaid more frequently presented with tumors >4 cm in size (11% versus 8%, P < 0.001) and regional metastases (29% versus 27%, P < 0.001). However, patients with Medicaid were also less likely to undergo appropriate surgical treatment (odds ratio 0.69, P < 0.001), less likely to undergo surgery within 90 d of diagnosis (hazard ratio 0.80, P < 0.001), and more likely to be undertreated with RAI (odds ratio 1.29, P < 0.001). There were no differences in the likelihood of guideline-concordant surgical or medical treatment by insurance type in patients ≥65 y old. CONCLUSIONS: In the era of the 2015 ATA guidelines, patients with Medicaid remain less likely to receive guideline-concordant, timely surgery and more likely to be undertreated with RAI compared to privately insured patients.

Adrenal Vein Sampling Results and Surgical Outcomes in Patients with a Normal Plasma Aldosterone Concentration.

PURPOSE: To determine the utility of adrenal vein sampling (AVS) and outcomes after adrenalectomy in patients with normal plasma aldosterone concentration (PAC) and elevated aldosterone-to-renin ratio (ARR). MATERIALS AND METHODS: The study sample included 106 patients with ARR greater than 20 and PAC between 5 and 15 ng/dL (normal PAC group) who underwent AVS from 2005 to 2021. These patients were compared with a cohort of 106 patients with ARR >20 and PAC >15 ng/dL (high PAC group) who underwent AVS during the same period. Data regarding baseline clinical characteristics, lateralization indices from AVS, and outcomes after adrenalectomy were analyzed. RESULTS: AVS was technically successful in 210 patients (210/212, 99%). A smaller proportion of patients in the normal PAC group showed a lateralization index of >4 compared with those in the high PAC group (44% vs 64%, P <.01). A similar proportion of patients in the normal PAC group experienced improved or cured hypertension after adrenalectomy compared with that in the high PAC group (94% vs 88%, P =.31). Hypokalemia was cured in all patients in the normal PAC group after adrenalectomy compared with 98% of patients in the high PAC group (100% vs 98%, P = 1). CONCLUSIONS: Although lateralization is less frequent for patients with normal PAC, patients who do lateralize show similar blood pressure response and correction of hypokalemia after adrenalectomy, regardless of initial plasma aldosterone levels. Therefore, patients with PAC <15 ng/dL should still be considered for AVS provided the ARR is elevated.

Survival After Adrenalectomy for Metastatic Lung Cancer.

BACKGROUND: Adrenal metastasectomy is associated with increased survival in non-small cell lung cancer (NSCLC) with isolated adrenal metastases. Although clinical use of adrenal metastasectomy has expanded, indications remain poorly defined. The aim of this study was to evaluate the clinical benefit of adrenal metastasectomy for all lung cancer subtypes. PATIENTS AND METHODS: We performed a retrospective cohort study of patients who underwent adrenal metastasectomy for metastatic lung cancer at six institutions between 2001 and 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Cox proportional hazards regressions and Kaplan-Meier survival analysis were performed. RESULTS: For 122 patients, the mean age was 60.5 years and 49.2% were female. Median time to detection of the metastasis was 11 months, and 41.8% were ipsilateral to the primary lung cancer. Median DFS was 40 months (1 year: 64.8%; 5 year: 42.9%). Factors associated with longer DFS included primary tumor resection [hazard ratio (HR): 0.001; p = 0.005], longer time to adrenal metastasis (HR: 0.94; p = 0.005), and ipsilateral metastases (HR: 0.13; p = 0.004). Shorter DFS corresponded with older age (HR: 1.11; p = 0.01), R1 resection (HR: 8.94; p = 0.01), adjuvant radiation (HR: 9.45; p = 0.02), and open adrenal metastasectomy (HR: 10.0; p = 0.03). Median OS was 47 months (1 year: 80.2%; 5 year: 35.2%). Longer OS was associated with ipsilateral metastasis (HR: 0.55; p = 0.02) and adjuvant chemotherapy (HR: 0.35; p = 0.02). Shorter OS was associated with extra-adrenal metastases at adrenalectomy (HR: 3.52; p = 0.007), small cell histology (HR: 15.0; p = 0.04), and lung radiation (HR: 3.37; p = 0.002). DISCUSSION: Durable survival was observed in patients undergoing adrenal metastasectomy and should be considered for isolated adrenal metastases of NSCLC. Small cell histology and extra-adrenal metastases are relative contraindications to adrenal metastasectomy.

New Operative Reporting Standards: Where We Stand Now and Opportunities for Innovation.

BACKGROUND: The American College of Surgeons Commission on Cancer's (CoC) new operative standards for breast cancer, melanoma, and colon cancer surgeries will require that surgeons provide synoptic documentation of essential oncologic elements within operative reports. Prior to designing and implementing an electronic tool to support synoptic reporting, we evaluated current documentation practices at our institution to understand baseline concordance with these standards. METHODS: Applicable procedures performed between 1 January 2018 and 31 December 2018 were included. Two independent reviewers evaluated sequential operative notes, up to a total of 100 notes, for documentation of required elements. Complete concordance (CC) was defined as explicit documentation of all required CoC elements. Mean percentage CC and surgeon-specific CC were calculated for each procedure. Interrater reliability was assessed via Cohen's kappa statistic. RESULTS: For sentinel lymph node biopsy, mean CC was 66% (n = 100), with surgeon-specific CC ranging from 6 to 100%, and for axillary dissection, mean CC was 12% (n = 89) and surgeon-specific CC ranged from 0 to 47%. The single surgeon performing melanoma wide local excision had a mean CC of 98% (n = 100). For colon resections, mean CC was 69% (n = 96) and surgeon-specific CC ranged from 39 to 94%. Kappa scores were 0.77, 0.78, -0.15, and 0.78, respectively. CONCLUSIONS: We identified heterogeneity in current documentation practices. In our cohort, rates of baseline concordance varied across surgeons and procedures. Currently, documentation elements are interspersed within the operative report, posing challenges to chart abstraction with resulting imperfect interrater reliability. This presents an exciting opportunity to innovate and improve compliance by introducing an electronic synoptic documentation tool.

How Referring Providers Choose Specialists for Their Patients: a Systematic Review.

BACKGROUND: Physician referrals are a critical step in directing patients to high-quality specialists. Despite efforts to encourage referrals to high-volume hospitals, many patients receive treatment at low-volume centers with worse outcomes. We aimed to determine the most important factors considered by referring providers when selecting specialists for their patients through a systematic review of medical and surgical literature. METHODS: PubMed and Embase were searched from January 2000 to July 2021 using terms related to referrals, specialty, surgery, primary care, and decision-making. We included survey and interview studies reporting the factors considered by healthcare providers as they refer patients to specialists in the USA. Studies were screened by two independent reviewers. Quality was assessed using the CASP Checklist. A qualitative thematic analysis was performed to synthesize common decision factors across studies. RESULTS: We screened 1,972 abstracts and identified 7 studies for inclusion, reporting on 1,575 providers. Thematic analysis showed that referring providers consider factors related to the specialist's clinical expertise (skill, training, outcomes, and assessments), interactions between the patient and specialist (prior experience, rapport, location, scheduling, preference, and insurance), and interactions between the referring physician and specialist (personal relationships, communication, reputation, reciprocity, and practice or system affiliation). Notably, studies did not describe how providers assess clinical or technical skills. CONCLUSIONS: Referring providers rely on subjective factors and assessments to evaluate quality when selecting a specialist. There may be a role for guidelines and objective measures of quality to inform the choice of specialist by referring providers.

Adrenalectomy for Secondary Malignancy: Patients, Outcomes, and Indications.

OBJECTIVE: The goal of this study was to examine a multi-institutional experience with adrenal metastases to describe survival outcomes and identify subpopulations who benefit from adrenal metastasectomy. BACKGROUND: Adrenalectomy for metastatic disease is well-described, although indications and outcomes are incompletely defined. METHODS: A retrospective cohort study was performed of patients undergoing adrenalectomy for secondary malignancy (2002-2015) at 6 institutions. The primary outcomes were disease free survival (DFS) and overall survival (OS). Analysis methods included Kaplan-Meier and Cox proportional hazards. RESULTS: Of 269 patients, mean age was 60.1 years; 50% were male. The most common primary malignancies were lung (n = 125, 47%), renal cell (n = 38, 14%), melanoma (n = 33, 12%), sarcoma (n = 18, 7%), and colorectal (n = 12, 5%). The median time to detection of adrenal metastasis after initial diagnosis of the primary tumor was 17 months (interquartile range: 6-41). Post-adrenalectomy, the median DFS was 18 months (1-year DFS: 54%, 5-year DFS: 31%). On multivariable analysis, lung primary was associated with longer DFS [hazard ratio (HR): 0.49, P = 0.008). Extra-adrenal oligometastatic disease at initial presentation (HR: 1.84, P = 0.016), larger tumor size (HR: 1.07, P = 0.013), chemotherapy as treatment of the primary tumor (HR: 2.07 P = 0.027) and adjuvant chemotherapy (HR: 1.95, P = 0.009) were associated with shorter DFS. Median OS was 53 months (1-year OS: 83%, 5-year OS: 43%). On multivariable analysis, extra-adrenal oligometastatic disease at adrenalectomy (HR: 1.74, P = 0.031), and incomplete resection of adrenal metastasis (R1 margins; HR: 1.62, P = 0.034; R2 margins; HR: 5.45, P = 0.002) were associated with shorter OS. CONCLUSIONS: Durable survival is observed in patients undergoing adrenal metastasectomy and should be considered for subjects with isolated adrenal metastases.

Endocrine Surgical Procedures During COVID-19: Patient Prioritization and Time to Surgery.

BACKGROUND: We tracked endocrine surgery patients with treatment delays due to COVID-19 to investigate the relationship between physician assigned priority scoring (PAPS), the Medically Necessary, Time Sensitive (MeNTS) scoring system and delay to surgery. MATERIAL & METHODS: Patients scheduled for endocrine surgery or clinically evaluated during COVID-19-related elective surgery hold at our institution (2/26/20-5/1/20) were prospectively enrolled. PAPS was assigned based on categories of high, moderate, or low risk, consistent with the American College of Surgeons' priority system. MeNTS scores were calculated. The primary outcome was delay to surgery. Descriptive statistics were performed, and receiver operator characteristic (ROC) curves and area under the curve (AUC) values were calculated for PAPS and MeNTS. RESULTS: Of 146 patients included, 68% (n = 100) were female; the median age was 60 years (IQR:43,67). Mean delay to surgery was significantly shorter (P = 0.01) in patients with high PAPS (35 d), compared with moderate (61 d) and low (79 d) PAPS groups. MeNTS scores were provided for 105 patients and were analyzed by diagnosis. Patients with benign thyroid disease (n = 17) had a significantly higher MeNTS score than patients with thyroid disease which was malignant/suspicious for malignancy (n = 44) patients (51.5 versus 47.6, P = 0.034). Higher PAPS correlated well with a delay to surgery of <30 d (AUC: 0.72). MeNTS score did not correlate well with delay to surgery <30 d (AUC: 0.52). CONCLUSION: PAPS better predicted delay to surgery than MeNTS scores. PAPS may incorporate more complex components of clinical decision-making which are not captured in the MeNTS score.

"Double-Down" Adrenal Vein Sampling Results in Patients with Apparent Bilateral Aldosterone Suppression: Utility of Repeat Sampling including Super-Selective Sampling.

PURPOSE: To report outcomes of patients undergoing adrenal vein sampling (AVS) for primary aldosteronism with results indicating apparent bilateral adrenal suppression (ABAS), in which the adrenal aldosterone-to-cortisol ratios are decreased bilaterally ("double-down") compared to the non-adrenal sample, and evaluate repeat AVS results. MATERIALS AND METHODS: Between 2003 and 2020, 762 patients underwent AVS. Twenty patients (2.6%; male, 12; female, 8; age 50.3 ± 9.7 years) with ABAS on initial AVS were identified. Ten underwent repeat AVS. Super-selective AVS (SS-AVS) was employed in 6 of 10 repeat AVS (60%). Outcomes after AVS were analyzed. A lateralization index (LI) >4 was considered an indication for adrenalectomy. RESULTS: Repeat AVS was diagnostic in 70% of patients (n = 7), with 6 of 7 lateralizing with LI >4 (median LI = 32.3; range 4.6-54.8) and 1 of 7 nearly lateralizing (LI = 3.5). All 7 patients underwent adrenalectomy. ABAS was redemonstrated in 3 patients (30%): 2 with unilateral adenomas on cross-sectional imaging underwent adrenalectomy despite ABAS results and 1 was lost to follow-up. Four of 6 patients (66%) who underwent SS-AVS were diagnosed with unilateral disease (median LI = 43.3; range 23.9-54.8), with one patient's diagnosis reliant upon a single super-selective sample. In total, 9 patients underwent adrenalectomy after repeat AVS, all of whom had improved blood pressure control postoperatively. Ten patients did not undergo repeat AVS: 6 were lost to follow-up, 3 underwent medical management, and 1 underwent adrenalectomy. CONCLUSIONS: AVS should be repeated when "double-down" ABAS results are encountered. Super-selective sampling may provide worthwhile diagnostic data when employed during repeat AVS.

Racial Disparities in Primary Hyperparathyroidism.

BACKGROUND: Racial disparities in surgery are increasingly recognized. We evaluated the impact of race on presentation, preoperative evaluation, and surgical outcomes for patients undergoing parathyroidectomy for primary hyperparathyroidism (PHPT). METHODS: We performed a retrospective cohort study of patients undergoing parathyroidectomy for PHPT at a single center (1997-2015). Patients were classified by self-identified race, as African-American or White. The primary outcome was disease severity at referral. The secondary outcome was completeness of preoperative evaluation. Operative success and surgical cure were evaluated. RESULTS: A total of 2392 patients were included. The majority of patients (87.6%) were White. African-American patients had higher rates of comorbid disease as well as higher preoperative calcium (10.9 vs.10.8 mg/dl, p < 0.001) and PTH levels (122 vs. 97 pg/ml, p < 0.001). White patients were more likely to have history of bone loss documented by DXA and nephrolithiasis. African-American patients had lower rates of complete preoperative evaluation including DXA scan. Operatively, African-American patients had larger glands by size (1.7 vs. 1.5 cm, p < 0.001) and mass (573 vs. 364 mg, p < 0.001). We observed similar operative success (98.9 vs. 98.0%, p = 0.355) and cure rates (98.3 vs. 97.0%, p = 0.756). CONCLUSIONS: At the time of surgical referral, African-American patients with PHPT have more biochemically severe disease and higher rates of incomplete evaluation. Operative success and cure rates are comparable.