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 PHPT and identify miRNA biomarkers of bone homeostasis. SUMMARY BACKGROUND DATA: Primary hyperparathyroidism (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 post-menopausal females with PHPT and control subjects matched for race, age, and 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, nine (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 to matched control subjects. All nine differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and eight of the nine 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 nine 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.

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.

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.

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 adenoma as a cause of primary hyperparathyroidism: Asymmetric hyperplasia or a distinct pathologic entity?

BACKGROUND: Primary hyperparathyroidism (PHPT) caused by double adenoma may carry a higher risk of failure to cure. We compared outcomes in single adenoma (SA), double adenoma (DA) and four-gland hyperplasia (HP). METHODS: Patients undergoing initial parathyroidectomy for PHPT were categorized by diagnosis. The primary outcome was persistent/recurrent disease postoperatively. RESULTS: Of 3408 patients, 81.3% had SA, 9.5% had DA, and 9.3% had HP. Rates of persistence/recurrence were 2.9%, 5.3%, and 4.5% in SA, DA, and HP, respectively (p = 0.281). Patients with persistence/recurrence had higher preoperative calcium (11.0 vs 10.7 mg/dl, p = 0.028) and PTH (96 vs 77 pg/ml, p = 0.015), and lower rates of IOPTH normalization (77% vs 96%, p < 0.001). On multivariable analysis, DA was associated with increased risk of persistent/recurrent disease (OR 3.0, p = 0.017). CONCLUSIONS: Most patients with DA are cured with removal of two glands, but approximately 5% experience disease persistence/recurrence. Low-normal final IOPTH was associated with lower risk of persistent/recurrent disease.

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.

Clinical presentation and surgical outcomes in primary aldosteronism differ by race.

BACKGROUND: Primary aldosteronism (PA) is the most common cause of secondary hypertension; early diagnosis and intervention correlate with outcomes. We hypothesized that race may influence clinical presentation and outcomes. METHODS: We conducted a retrospective analysis of patients with PA (1997-2017) who underwent adrenal vein sampling (AVS). Patients were classified by self-reported race as black or non-black. Improvement was defined as postoperative decrease in mean arterial pressure (MAP), antihypertensive medications (AHM), or both. RESULTS: Among patients undergoing AVS (n = 443), 287 underwent adrenalectomy. Black patients (28.2%) had higher body mass index (33.9 vs 31.8 kg/m2 ; P = .01), longer median duration of hypertension (12 vs 10 years; P = .003), higher modified Elixhauser comorbidity index (2 vs 1; P = .004), and lower median income ($47 134 vs $78 280; P < .001). Black patients had similar aldosterone:renin ratios (150 vs 135.6 [ng/dL]/[ng·mL·-1 hr-1 ]; P = .23) compared to non-blacks. At long-term follow-up, black patients had a similar requirement for AHM (1 vs 0; P = .13) but higher MAP (100.6 vs 95.3 mm Hg; P = .004). CONCLUSION: Black patients present with longer duration of hypertension and more comorbidities. They are equally likely to lateralize on AVS, suggesting similar disease phenotype. However, black patients demonstrate less improvement with adrenalectomy; this may reflect a delay in diagnosis or concomitant essential hypertension.

Intraoperative Parathyroid Hormone Monitoring in Parathyroidectomy for Tertiary Hyperparathyroidism.

BACKGROUND: Tertiary hyperparathyroidism (THPT) is characterized by hypercalcemia and hyperparathyroidism after renal allograft. Limited data exist regarding the use of intraoperative parathyroid hormone (IOPTH) for THPT. We examined our series of parathyroidectomies performed for THPT to determine clinical outcomes with respect to IOPTH. MATERIALS AND METHODS: Patients who underwent parathyroidectomy for THPT (1999-2017) were identified for inclusion. Retrospective chart review was performed. Cure was defined as eucalcemia ≥6 mo after surgery. Statistical analysis was performed. RESULTS: Of 41 patients included in the study, 41% (n = 17) were female. The median duration of dialysis before renal allograft was 34 mo (interquartile interval [IQI]:6-60). Preoperatively, the median calcium level was 10.4 mg/dL (IQI:10.0-11.2), median parathyroid hormone was 172 pg/mL (IQI:104-293), and renal function was minimally abnormal with median glomerular filtration rate 58 mL/min/1.73 m2 (IQI:49-71). At surgery, the median final IOPTH was 40 pg/mL (IQI:29-73), and median decrease in IOPTH was 78% (IQI:72-87), with 88% (n = 36) of patients demonstrating >50% decrease. Median calcium level ≥6 mo after surgery was 9.4 mg/dL (IQI:8.8-9.7), and only one patient had recurrent hypercalcemia. Failure to achieve >50% decrease in IOPTH was not significantly associated with recurrent hypercalcemia (P = 1.000). With a median follow-up time of 41 mo (IQI:25-70), only three patients had graft failure. The positive predictive value of IOPTH for cure was 89% (95% confidence interval: 0.752-0.971), with 0% negative predictive value and 87% accuracy (95% confidence interval: 0.726-0.957). CONCLUSIONS: Subtotal parathyroidectomy is a successful operation with durable cure of THPT. IOPTH fails to predict long-term cure in THPT despite minimally abnormal renal function.