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.

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.

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.

Neoadjuvant Chemotherapy in Retroperitoneal Sarcoma: A National Cohort Study.

INTRODUCTION: Management of retroperitoneal sarcoma (RPS) remains controversial, with the mainstay of treatment being surgery. While neoadjuvant radiation demonstrated no improvement in recurrence-free survival in a prospective randomized trial (STRASS), the role of neoadjuvant chemotherapy (NCT) remains unknown and is the subject of ongoing study (STRASS2). METHODS: Patients who underwent surgical resection of high-grade RP leiomyosarcoma (LMS) or dedifferentiated liposarcoma (DDLS) were identified from the National Cancer Database (2006-2019). Predictors of NCT were analyzed using univariate and multivariate logistic regression analyses. Differences in 5-year survival were examined using the Kaplan-Meier (KM) method and by Cox proportional hazard modeling. RESULTS: A total of 2656 patients met inclusion criteria. Fifty-seven percent of patients had DDLS and 43.5% had LMS. Six percent of patients underwent NCT. Patients who received NCT were younger (median age 60 vs 64 years, p < 0.001) and more likely to have LMS (OR 1.4, p = 0.04). In comparing NCT with no-NCT patients, there was no difference in 5-year overall survival (OS) on KM analysis (57.3% vs 52.8%, p = 0.38), nor was any difference seen after propensity matching (54.9% vs 49.1%, p = 0.48, N = 144 per group). When stratified by histology, there was no difference in OS based on receipt of NCT (LMS: 59.8% for NCT group, 56.6% for no-NCT, p = 0.34; DDLS: 54.2% for NCT group, 50.1% for no-NCT, p = 0.99). CONCLUSION: In patients undergoing surgical resection of RP LMS or DDLS, NCT does not appear to confer an OS advantage. Prospective randomized data from STRASS2 will confirm or refute these retrospective data.

Surgical Outcomes in Patients With Malignant Small Bowel Obstruction: A National Cohort Study.

OBJECTIVE: The study objectives were to characterize surgical outcomes for malignant small bowel obstruction (MaSBO) as compared to other small bowel obstructions (SBO) and to develop a prediction model for postoperative mortality for MaSBO. SUMMARY BACKGROUND DATA: MaSBO is a morbid complication of advanced cancers for which the optimal management remains undefined. METHODS: Patients who underwent surgery for MaSBO or SBO were identified from the National Surgical Quality Improvement Program (2005-2017). Outcomes [30-day morbidity, unplanned readmissions, mortality, postoperative length of stay (LOS)] were compared between propensity score-matched MaSBO and SBO patients. An internally validated prediction model for mortality in MaSBO patients was developed. RESULTS: Of 46,706 patients, 1612 (3.5%) had MaSBO. Although MaSBO patients were younger than those with SBO (median 63 vs 65 years, P < 0.001), they were otherwise more clinically complex, including a higher proportion with recent weight loss (22.0% vs 4.0%, P < 0.001), severe hypoalbuminemia (18.6% vs 5.2%, P < 0.001), and cytopenias. After matching (N = 1609/group), MaSBO was associated with increased morbidity [odds ratio (OR) 1.2, P = 0.004], but not readmission (OR 1.1, P = 0.48) or LOS (incidence rate ratio 1.0, P = 0.14). The odds of mortality were significantly higher for MaSBO than SBO (OR 3.3, P < 0.001). A risk-score model predicted postoperative mortality for MaSBO with an optimism-adjusted Brier score of 0.114 and area under the curve of 0.735. Patients in the highest-risk category (11.5% of MaSBO population) had a predicted mortality rate of 39.4%. CONCLUSION: Surgery for MaSBO is associated with substantial morbidity and mortality, necessitating careful patient evaluation before operative intervention.

Are Volume Pledge Standards Worth the Travel Burden for Major Abdominal Cancer Operations?

OBJECTIVE: The study objective is to determine the association between travel distance and surgical volume on outcomes after esophageal, pancreatic, and rectal cancer resections. SUMMARY OF BACKGROUND DATA: "Take the Volume Pledge" aims to centralize esophagectomies, pancreatectomies, and proctectomies to hospitals meeting minimum volume standards. The impact of travel, and possible care fragmentation, on potential benefits of centralized surgery is not well understood. METHODS: Using the National Cancer Database (2004-2016), patients who underwent esophageal, pancreatic, or rectal resections at far HVH meeting volume standards versus local intermediate (IVH) and low-volume (LVH) hospitals were identified. Perioperative outcomes and 5-year OS were compared. RESULTS: Of 49,454 patients, 17,544 (34.5%) underwent surgery at far HVH, 11,739 (23.7%) at local IVH, and 20,171 (40.8%) at local LVH. The median (interquartilerange) travel distances were 77.1 (51.1-125.4), 13.2 (5.8-27.3), and 7.8 (3.1-15.5) miles to HVH, IVH, and LVH, respectively. By multivariable analysis, LVH was associated with increased 30-day mortality for all resections compared to HVH, but IVH was associated with mortality only for proctectomies [odds ratio 1.90, 95% confidence interval (CI) 1.31-2.75]. Compared to HVH, both IVH (hazard ratio 1.25, 95% CI 1.19-1.31) and LVH (hazard ratio 1.35, 95% CI 1.29-1.42) were associated with decreased 5-year OS. CONCLUSIONS: Compared to far HVH, 30-day mortality was higher for all resections at LVH, but only for proctectomies at IVH. Five-year OS was consistently worse at local LVH and IVH. Improving long-term outcomes at IVH may provide opportunities for greater access to quality cancer care.

Pathologic Factors Associated with Low Risk of Lymph Node Metastasis in Nonmucinous Adenocarcinoma of the Appendix.

BACKGROUND: Right hemicolectomy (RHC) for nodal staging is recommended for nonmucinous adenocarcinoma of the appendix (NMACA), but it is unclear whether a subgroup of patients at low risk for lymph node (LN) metastasis exists who may be managed with a less extensive resection. PATIENTS AND METHODS: Patients with NMACA without distant metastases who underwent margin negative resection via either RHC or appendectomy/partial colectomy (A/PC) were evaluated from the National Cancer Database (2004-2016). Patients at low risk for LN metastasis were identified. Multivariable survival analysis was performed, and 5-year overall survival (OS) was estimated. RESULTS: Of the 2487 patients included, 652 [26.2%; 95% confidence interval (CI) 24.5-28.0%] had LN metastases. T4 T stage [odds ratio (OR) 4.2, p = 0.032], poorly/undifferentiated histology (OR 2.2, p = 0.004), and lymphovascular invasion (LVI) (OR 4.4, p < 0.001) were associated with LN positivity. One hundred and thirteen patients (4.5%) had tumors at low risk for LN metastasis (T1 T stage, well/moderately differentiated tumors without LVI), and the rate of LN metastasis for this group was 1.8% (95% CI 0.5-6.2%). Conversely, the LN metastasis rate among the 2374 non-low-risk patients was 27.4% (95% CI 25.6-29.2%). Performance of A/PC instead of RHC was associated with a survival disadvantage among all patients (hazards ratio 1.5, p = 0.049), but among the low-risk cohort, 5-year OS did not differ based on resection type (88.3% A/PC versus 92.7% RHC, p = 0.305). CONCLUSIONS: Although relatively uncommon, early, pathologically favorable NMACA is associated with a very low risk of LN metastasis. These select patients may be managed with a less extensive resection without compromising oncologic outcomes.

Lymph Node Evaluation after Neoadjuvant Chemotherapy for Patients with Gastric Cancer.

BACKGROUND: Adequate lymphadenectomy with at least 16 nodes retrieved at the time of gastrectomy is a quality measure recommended to ensure adequate staging. The minimum nodal retrieval recommended after receipt of neoadjuvant chemotherapy (NACT) is less defined. METHODS: Patients with clinical stages 1 to 3 gastric adenocarcinoma who received NACT and surgical resection were identified from the 2004-2015 National Cancer Database. The optimal nodal harvest number was calculated with Cox spline regression modeling. Cohorts with a nodal harvest higher or lower than this number were 1:1 propensity score-matched. Overall survival (OS) was analyzed using Kaplan-Meier survival estimates. RESULTS: Among 4337 patients receiving NACT, the optimal minimal nodal harvest at gastrectomy was 23 nodes. Compared with the patients who had fewer than 23 nodes retrieved, the patients with at least 23 nodes examined (n = 1073, 24.7%) were more likely to be female (26.1% vs 22%; p = 0.006) and non-white (29.3% vs 18.5%; p < 0.0001), to have a Charlson-Deyo score of 0 (71.5% vs 66.8%; p = 0.005), and to have undergone resection at an academic facility (67.9% vs 51.5%; p < 0.0001). The patients with at least 23 nodes examined had higher proportions of high-grade tumor (62% vs 57.4%; p = 0.030), pT3 or pT4 tumor (56.3% vs 48.7%; p < 0.0001), body tumor (21.3% vs 12.5%; p < 0.0001), or antrum/pylorus tumor (15.3% vs 11.4%; p < 0.0001). The patients with at least 23 nodes were more likely to have lymph node metastases identified (61% vs 51%; p < 0.0001). After matching, the patients with at least 23 nodes (n = 990) demonstrated an improved 5-year OS (57.9% vs 49%; p = 0.001). CONCLUSIONS: The extent of lymphadenectomy during gastrectomy for gastric adenocarcinoma should not be reduced after NACT because adequate lymph node retrieval remains important for prognostication.

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.

The impact of hospital volume on racial disparities in resected rectal cancer.

BACKGROUND: Although high volume centers (HVC) equate to improved outcomes in rectal cancer, the impact of surgical volume related to race is less defined. METHODS: Patients who underwent surgical resection for stage I-III rectal adenocarcinoma were divided into cohorts based on race and hospital surgical volume. Outcomes were analyzed following 1:1 propensity-score matching using logistic, Poisson, and Cox regression analyses with marginal effects. RESULTS: Fifty-four thousand one hundred and eighty-four (91.5%) non-Black and 5043 (8.5%) Black patients underwent resection of rectal cancer. Following 1:1 matching of non-Black (N = 5026) and Black patients, 5-year overall survival (OS) of Black patients was worse (72% vs. 74.4%, average marginal effects [AME] 0.66, p = 0.04) than non-Black patients. When compared to non-Black patients managed at HVCs, Black patients had worse OS (70.1% vs. 74.7%, AME 1.55, p = 0.03), but this difference was not significant when comparing OS between non-Black and Black patients managed at HVCs (72.3% vs. 74.7%, AME 0.62, p = 0.06). Length of stay was longer among Black and HVC patients across all cohorts. There was no difference across cohorts in 90-day mortality. CONCLUSIONS: Although racial disparities exist in rectal cancer, this disparity appears to be ameliorated when patients are managed at HVCs.

Neoadjuvant radiation for cutaneous and soft tissue angiosarcoma.

BACKGROUND AND OBJECTIVES: Neoadjuvant radiation (NRT) is frequently utilized in soft tissue sarcomas to increase local control. Its utility in cutaneous and soft tissue angiosarcoma remains poorly defined. METHODS: This retrospective cohort study was performed using the National Cancer Database (2004-2016) evaluating patients with clinically localized, surgically resected angiosarcomas. Factors associated with receipt of NRT in the overall cohort and margin positivity in treatment naïve patients were identified by univariate and multivariable logistic regression analyses. Survival was assessed using Kaplan-Meier analysis. RESULTS: Of 597 patients, 27 (4.5%) received NRT. Increasing age (odds ratio [OR] 0.95, p = 0.025), tumor size more than or equal to 5 cm (OR 3.16, p = 0.02), and extremity tumor location (OR 3.99, p = 0.04) were associated with receipt of NRT. All patients who received NRT achieved an R0 resection (p = 0.03) compared with 17.9% of patients without NRT. Factors associated with risk of margin positivity included tumor size more than or equal to 5 cm (OR 1.85, p = 0.01), and head/neck location (OR 2.24, p = 0.006). NRT was not significantly associated with improved survival (p = 0.21). CONCLUSIONS: NRT improves rates of R0 resection but is infrequently utilized in cutaneous and soft tissue angiosarcoma. Increased usage of NRT, particularly for patients with lesions more than or equal to 5 cm, or head and neck location, may help achieve complete resections.

Opioid Use Disorder is Associated With Complications and Increased Length of Stay After Major Abdominal Surgery.

OBJECTIVE: The objective of this study was to determine the impact of opioid use disorder (OUD) on perioperative outcomes after major upper abdominal surgeries. SUMMARY OF BACKGROUND DATA: OUD, defined as dependence/abuse, is a national health epidemic. Its impact on outcomes after major abdominal surgery has not been well characterized. METHODS: Patients who underwent elective esophagectomy, total/partial gastrectomy, major hepatectomy, and pancreatectomy were identified using the National Inpatient Sample (2003-2015). Propensity score matching by baseline characteristics was performed for patients with and without OUD. Outcomes measured were in-hospital complications, mortality, length of stay (LOS), and discharge disposition. RESULTS: Of 376,467 patients, 1096 (0.3%) had OUD. Patients with OUD were younger (mean 53 vs 61 years, P < 0.001) and more often male (55.1% vs 53.2%, P < 0.001), black (15.0% vs 7.6%, P < 0.001), Medicaid beneficiaries (22.0% vs 6.4%, P < 0.001), and in the lowest income quartile (32.6% vs 21.3%, P < 0.001). They also had a higher rate of alcohol (17.2% vs 2.8%, P < 0.001) and nonopioid drug (2.2% vs 0.2%, P = 0.023) dependence/abuse. After matching (N = 1077 OUD, N = 2164 no OUD), OUD was associated with a higher complication rate (52.9% vs 37.3%, P < 0.001), including increased pain [odds ratio (OR) 3.5, P < 0.001], delirium (OR 3.0, P = 0.004), and pulmonary complications (OR 2.0, P = 0.006). Additionally, OUD was associated with increased LOS (mean 12.4 vs 10.6 days, P = 0.015) and nonroutine discharge (OR 1.6, P < 0.001). In-hospital mortality did not differ (OR 2.4, P = 0.10). CONCLUSION: Patients with OUD more frequently experienced complications and increased LOS. Close postoperative monitoring may mitigate adverse outcomes.

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.

Patterns of Metastasis in Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied. METHODS: Patients with American Joint Committee on Cancer (8th edition) stage I-IV MCC treated at our institution were identified (1/1/2008-2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated. RESULTS: Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20-66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002). CONCLUSIONS: Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.

Gastric Neuroendocrine Tumors: Reappraisal of Type in Predicting Outcome.

BACKGROUND: Type I gastric neuroendocrine tumors (GNETs) are typically managed either expectantly or endoscopically. In contrast, locoregional surgery has been recommended for patients with type III GNETs because of the risk of metastasis. This study aimed to identify predictors of outcome independent of type in a contemporary cohort of GNET patients. METHODS: A single-institution retrospective cohort study of 121 patients with a pathologic diagnosis of primary GNET between January 2009 and June 2019 was performed. GNETs were designated as type 1 (n = 74) if atrophic gastritis was present, or as type III (n = 47) in the absence of atrophic gastritis. Demographic, clinical, and histopathologic factors were examined using Kaplan-Meier and multivariable Cox regression to assess the impact of various factors on recurrence and overall survival. RESULTS: Median follow-up for the entire cohort was 62.7 months. While there was no difference in OS in patients with different GNET types (p = 0.10), higher tumor grade (p = 0.02) and presence of nodal or distant metastases (p = 0.02) predicted worse survival on multivariable analysis. Among type III GNET patients, those with small (< 0.5 cm), grade 1 lesions ("low-risk") were less likely to develop metastases (0% versus 33%, p < 0.01) and more likely to survive (100% versus 67%, p < 0.01) at 5 years. CONCLUSIONS: Size and tumor grade predict recurrence and survival in patients with GNETs irrespective of type. Small, low-grade type III GNETs are associated with minimal risk of progression and may be managed accordingly.

Preoperative Biopsy in Patients with Retroperitoneal Sarcoma: Usage and Outcomes in a National Cohort.

INTRODUCTION: Preoperative biopsy (PBx) is often recommended for retroperitoneal sarcoma (RPS), but its utilization rate and impact on perioperative management and outcomes remains undefined. METHODS: Using the National Cancer Database, patients who underwent resection of non-metastatic RPS were identified (2006-2014). Patients who did and did not undergo PBx of the primary tumor were compared using propensity matching, and factors associated with survival were assessed by multivariable analysis. RESULTS: Of 2620 patients, 1110 (42.4%) underwent PBx. Factors significantly associated with performance of PBx included male sex [odds ratio (OR) 1.2, P = 0.035], tumor size ≤ 5 cm (OR 1.5, P = 0.012), tumor size > 5 to ≤ 10 cm (OR 1.3, P = 0.009), non-well-differentiated liposarcoma histology (OR 2.0, P ≤ 0.001), and treatment at a high-volume center (OR 1.3, P = 0.021). Receipt of PBx was significantly associated with administration of neoadjuvant radiation (OR 8.8, P < 0.001) or systemic therapy (OR 3.3, P < 0.001), radical surgical resection (OR 1.6, P < 0.001), and complete tumor resection (OR 1.5, P < 0.003). Neoadjuvant radiation [hazard ratio (HR) 0.7, P = 0.003] and complete tumor resection (HR 0.6, P < 0.001) were significantly associated with improved overall survival (OS). Performance of PBx was not associated with OS (HR 1.1, P = 0.070), and following propensity matching, 5-year OS did not differ between the two groups (56.5% PBx vs 58.4% no PBx, P = 0.247). CONCLUSIONS: A minority of patients with non-metastatic RPS undergo PBx. PBx does not negatively impact survival, but may indirectly improve outcomes in select patients by virtue of receipt of neoadjuvant therapy and attainment of complete tumor resection.

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.

National trends in the presentation of surgically resected appendiceal adenocarcinoma over a decade.

BACKGROUND: Rates of nonoperative management of acute appendicitis and appendiceal adenocarcinoma have increased over a decade, but the presentation and outcomes of appendiceal adenocarcinoma over this period is not well-characterized. METHODS: Patients with surgically resected Stage I-III appendiceal adenocarcinoma were identified from the 2006 to 2015 National Cancer Data Base and classified into two cohorts, 2006-2010 and 2011-2015, based on year of diagnosis. Three-year overall survival (OS) was analyzed using Cox proportional hazards regression and Kaplan-Meier survival estimates. RESULTS: Of 4233 patients, 1369 (32.3%) and 2864 (67.7%) were diagnosed in 2006-2010 and 2011-2015, respectively. Following multivariable analysis, patients in 2011-2015 were more likely to be <40 years of age (6.4% vs. 4.7%, odds ratio [OR] 1.53, p .015), present with pT4 tumors (40.2% vs. 34.4%, OR 1.46, p .004), and undergo hyperthermic intraperitoneal chemotherapy (4.4% vs. 2.4%, OR 1.97, p .001). Comparing patients diagnosed in 2011-2015 to 2006-2010, adjusted 3-year OS was no different among all patients (81.1% vs. 79%, p .778). CONCLUSIONS: There has been an increase in the proportion of patients with pT4 appendix tumors over time, primarily among older (≥60 years) patients. Even so, these shifts in presentation have not resulted in differences in survival outcomes.

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.