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We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional program, including Ednrb expression. Heme is a known inhibitor of Bach1, and, correspondingly, heme exposure induced Ednrb and iTAM signature genes in macrophages. Thus, iTAMs are a distinct macrophage subset regulated by the transcription factor Bach1 and characterized by Ednrb-mediated immunosuppressive and angiogenic functions., (© 2024 Folkert et al.)

Background: Normohormonal primary hyperparathyroidism is characterized by hypercalcemia and inappropriately normal parathyroid hormone levels. We previously reported that intraoperative parathyroid hormone decline of 50-70% for normohormonal and 75-88% for classic primary hyperparathyroidism during parathyroidectomy was predictive of (1) cure and (2) avoidance of hypocalcemia in a single-institution study (derivation cohort). We sought to externally validate these findings., Methods: We performed a multi-institutional retrospective cohort study of patients undergoing parathyroidectomy for primary hyperparathyroidism from 2002 to 2019 (validation cohort). Primary outcomes were biochemical cure (calcium <10.3 mg/dL) and postoperative hypocalcemia (≤8.8 mg/dL) ≥6 months postoperatively. Test characteristics of the previously derived thresholds were evaluated in this cohort., Results: A total of 163 (16%) of 1,037 patients had normohormonal primary hyperparathyroidism. Cure rates were similar for normohormonal and classic primary hyperparathyroidism (94% vs 92%, P = .41). In patients who were cured, the median intraoperative parathyroid hormone decrease was lower in normohormonal compared with classic primary hyperparathyroidism (56.8 vs 73.3%, P < .0001). Rates of hypocalcemia were similar for normohormonal and classic primary hyperparathyroidism (14.6% vs 11.9%, P = .44), but increasing percent intraoperative parathyroid hormone decrease beyond 65% disproportionately correlated with hypocalcemia in patients with normohormonal primary hyperparathyroidism. When intraoperative parathyroid hormone thresholds from the derivation cohort were applied, positive predictive values for cure were 97% and 94% for normohormonal and classic primary hyperparathyroidism, respectively; negative predictive values for hypocalcemia were 89% for both groups. For both cohorts combined, a minimal intraoperative parathyroid hormone of 50% provided similar cure rates between groups (95.4% vs 93.8%, P = .42), whereas intraoperative parathyroid hormone exceeding 65% correlated with a greater risk of hypocalcemia in normohormonal compared with classic primary hyperparathyroidism (13.4% vs 6.9%, P = .02)., Conclusion: This multi-institutional study externally validated that intraoperative parathyroid hormone decrease of 50-65% predicts cure and hypocalcemia in patients with normohormonal primary hyperparathyroidism., Competing Interests: Conflicts of Interest/Disclosure The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: T.L.A.K. is a paid employee of Hologic Inc., Marlborough, MA. M.H. is a shareholder and CEO/CSO of TAmiRNA GmbH, Vienna, Austria. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study assessed for disparities in the presentation and management of medullary thyroid cancer (MTC)., Methods: Patients with MTC (2010-2020) were identified from the National Cancer Database. Differences in disease presentation and likelihood of guideline-concordant surgical management (total thyroidectomy and resection of ≥1 lymph node) were assessed by sex and race/ethnicity., Results: Of 6154 patients, 68.2% underwent guideline-concordant surgery. Tumors >4 ​cm were more likely in men (vs. women: OR 2.47, p ​< ​0.001) and Hispanic patients (vs. White patients: OR 1.52, p ​= ​0.001). Non-White patients were more likely to have distant metastases (Black: OR 1.63, p ​= ​0.002; Hispanic: OR 1.44, p ​= ​0.038) and experienced longer time to surgery (Black: HR 0.66, p ​< ​0.001; Hispanic: HR 0.71, p ​< ​0.001). Black patients were less likely to undergo guideline-concordant surgery (OR 0.70, p ​= ​0.022)., Conclusions: Male and non-White patients with MTC more frequently present with advanced disease, and Black patients are less likely to undergo guideline-concordant surgery., Competing Interests: Declaration of competing interest Saiesh Kalva, Sara P. Ginzberg, Jesse E. Passman, Jacqueline M. Soegaard Ballester, Caitlin B. Finn, Douglas L. Fraker, Rachel R. Kelz, and Heather Wachtel have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study assessed the relationship between surgeon volume, operative management, and resource utilization in adrenalectomy., Methods: Isolated adrenalectomies performed within our health system were identified (2016-2021). High-volume surgeons were defined as those performing ≥6 cases/year. Outcomes included indication for surgery, perioperative outcomes, and costs., Results: Of 476 adrenalectomies, high-volume surgeons (n ​= ​3) performed 394, while low-volume surgeons (n ​= ​12) performed 82. High-volume surgeons more frequently operated for pheochromocytoma (19% vs. 16%, p ​< ​0.001) and less frequently for metastasis (6.4% vs. 23%, p ​< ​0.001), more frequently used laparoscopy (95% vs. 80%, p ​< ​0.001), and had lower operative supply costs ($1387 vs. $1,636, p ​= ​0.037). Additionally, laparoscopic adrenalectomy was associated with shorter length of stay (-3.43 days, p ​< ​0.001), lower hospitalization costs (-$72,417, p ​< ​0.001), and increased likelihood of discharge to home (OR 17.03, p ​= ​0.008)., Conclusions: High-volume surgeons more often resect primary adrenal pathology and utilize laparoscopy. Laparoscopic adrenalectomy is, in turn, associated with decreased healthcare resource utilization., Competing Interests: Declaration of competing interest Sara P. Ginzberg, Julia A. Gasior, Lauren R. Kelz, Jesse E. Passman, Jacqueline M. Soegaard Ballester, Robert E. Roses, Douglas L. Fraker, and Heather Wachtel have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Outpatient thyroidectomy is increasingly favored, given evidence of safety and convenience for selected patients. However, the prevalence of same-day discharge is unclear. We aimed to evaluate temporal trends, hospital characteristics, and costs associated with same-day discharge after total thyroidectomy in an all-payer, multi-state cohort., Methods: We included patients aged ≥18 years who underwent a total thyroidectomy (2013-2019) using Healthcare Cost and Utilization Project data. Admission type was defined as same-day, overnight, or inpatient based on length of stay. Same-day patients were propensity-score matched 1:1 with overnight patients. Hospital characteristics and costs were compared in the matched cohort., Results: Among 86,187 patients who underwent total thyroidectomy, 16,743 (19.4%) cases were same-day, 59,778 (69.4%) were overnight, and 9,666 (11.2%) were inpatient. The proportion of patients who underwent same-day thyroidectomy increased from 14.8% to 20.8% over the study period (P < .001), whereas overnight admissions decreased from 72.9% to 68.8% (P < .001). In total, 9,571 same-day patients were matched to 9,571 overnight patients. Same-day patients had higher odds of treatment at a certified cancer center (odds ratio 1.77; 95% confidence interval 1.65-1.90), Accreditation Council for Graduate Medical Education-accredited teaching hospital (odds ratio 1.72; 95% confidence interval 1.61-1.85), and high-volume hospital (odds ratio 1.53; 95% confidence interval 1.42-1.65). Pairwise cost differences showed median savings of $974 (interquartile range -1,610 to 3,491) for same-day relative to overnight admission (P < .001)., Conclusion: Although over two-thirds of patients are admitted overnight, same-day total thyroidectomy is increasingly performed. Same-day thyroidectomy may be a lower-cost option for selected patients, particularly in specialty centers with experience in thyroidectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023. Society of Surgical Oncology.)

Background: Reoperative parathyroidectomy for recurrent/persistent primary hyperparathyroidism (PHPT) has high rates of failure. The goal of this study was to analyze our experience with imaging and parathyroid vein sampling (PAVS) for recurrent/persistent PHPT., Methods: We performed a retrospective cohort study (2002-2018) of patients with recurrent/persistent PHPT undergoing reoperative parathyroidectomy., Results: Among 181 patients, the most common imaging study was sestamibi (89.5%), followed by ultrasound (75.7%). CT had the highest rate of localization (70.8%) compared to sestamibi (58.0%) and ultrasound (47.4%). PAVS was performed in 25 patients, and localized in 96%. Ultrasound and sestamibi both demonstrated 62% PPV for operative pathology, compared to 41% in CT. PAVS was 95% sensitive with 95% PPV for predicting the correct side of abnormal parathyroid tissue., Conclusions: We recommend a sequential imaging evaluation for reoperative parathyroidectomy, with sestamibi and/or ultrasound followed by CT. PAVS should be considered if non-invasive imaging fails to localize., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023. Society of Surgical Oncology.)

Background: In normohormonal primary hyperparathyroidism, parathyroid hormone levels are normal but inappropriately elevated for the degree of hypercalcemia. The study goals were to determine intraoperative parathyroid hormone parameters predictive of (1) cure and (2) hypocalcemia in this subgroup., Methods: We performed a retrospective cohort study comparing patients who underwent parathyroidectomy (2002-2019) for normohormonal and classic primary hyperparathyroidism. The primary outcomes were cure (calcium <10.3 mg/dL) and hypocalcemia (≤8.4 mg/dL) ≥6 months postoperatively., Results: In the study, 127 of 1,087 patients (11.7%) had normohormonal primary hyperparathyroidism. The groups experienced similar rates of cure (91.3% vs 94.1%, P = .23) and hypocalcemia (3.9% vs 2.9%, P = .53). However, intraoperative parathyroid hormone decline in cured patients was lower in those with normohormonal primary hyperparathyroidism (66.4% vs 84.5%, P < .0001). Receiver operating characteristic curves provided Youden's indices of 52% and 75% (cure) and 75% and 88% (hypocalcemia) for patients with normohormonal and classic primary hyperparathyroidism, respectively. Cure rates with ≥50% intraoperative parathyroid hormone decline were similar (94.1% vs 95.0%, P = .72), but hypocalcemia was more prevalent in patients with normohormonal primary hyperparathyroidism and ≥70% intraoperative parathyroid hormone decline (10.4% vs 3.3%, P = .01)., Conclusion: In patients with normohormonal primary hyperparathyroidism, intraoperative parathyroid hormone declines of ≥50% and ≥70% were predictive of postoperative cure and hypocalcemia, respectively. These parameters may inform intraoperative decision making and postoperative management., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Adjuvant systemic therapy is selectively considered for high-risk stage II colon cancer, but which patients benefit most from adjuvant systemic therapy is unclear., Methods: Patients who underwent resection of stage II colon cancer were identified from the National Cancer Database (2010-2016). Risk-factors for decreased overall survival on multivariable analysis were used to establish a predictive risk-score model for all-cause mortality. After propensity matching within each risk group, 5-year overall survival was estimated based on receipt of adjuvant systemic therapy., Results: Of the 15,241 patients evaluated, 2,857 (18.8%) received adjuvant systemic therapy. Risk factors for decreased overall survival included age >75 (hazard ratio 3.3, P < .001), male sex (hazard ratio 1.2, P < .001), White/Black race (hazard ratio 1.4, P = .020), preoperative carcinoembryonic antigen >3.5 ng/mL (hazard ratio 1.6, P < .001), T4a T-stage (hazard ratio 2.0, P < .001), T4b T-stage (hazard ratio 2.4, P < .001), lymphovascular invasion (hazard ratio 1.2, P = .003), perineural invasion (hazard ratio 1.3, P = .003), and non-R0 proximal/distal resection margins (hazard ratio 1.7, P < .001). An internally validated risk-score model using these factors was developed composed of low-risk (n = 8,489), moderate-risk (n = 4,623), and high-risk (n = 2,129) groups; within each group, 19.9%, 15.7%, and 20.8% of patients, respectively, received adjuvant systemic therapy. After propensity matching, adjuvant systemic therapy was not associated with improved 5-year overall survival for low-risk patients (89.8% vs 88.3%, P = .280), but was for moderate-risk (80.5% vs 70.8%, P < .001), and high-risk (65.2% vs 45.7%, P < .001) patients., Conclusion: A predictive risk-score model incorporating patient and tumor factors identifies a high-risk cohort of stage II colon cancer patients who may benefit from adjuvant systemic therapy, although the minority of these patients appear to be receiving treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The incidence of, and factors associated with, lymph node metastasis (LN+) in non-functional gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are not well characterized., Methods: Patients were identified from the 2010-2015 National Cancer Database who underwent surgical resection with lymphadenectomy for clinical stage I-III non-functional GEP NETs. Among a randomly selected training subset of 75% of the study population, variables associated with LN+ were identified using multivariable logistic regression analysis, and these variables were used to create a risk-score model for LN+, which was internally validated among the remaining 25% of the cohort., Results: Of 12,228 patients evaluated, 6,902 (56.4%) had LN+. Among the training set, variables associated with LN+ included age (70 years of age or older: odds ratio [OR] 1.12, 95% CI 1.00-1.24; ref: less than 70 years), tumor location (stomach: OR 3.72, 95% CI 2.94-4.71; small intestine: OR 19.60, 95% CI 17.31-22.19; ref: pancreas), tumor grade (moderately differentiated: OR 1.47, 95% CI 1.30-1.67; poorly differentiated/anaplastic: OR 1.53, 95% CI 1.21-1.95; ref: well-differentiated), tumor size (2-4 cm: OR 2.40, 95% CI 2.13-2.70; >4 cm: OR 5.25, 95% CI 4.47-6.17; ref: <2 cm), and lymphovascular invasion (OR 5.62, 95% CI 5.08-6.21; ref: no lymphovascular invasion). After internal validation, a risk-score model for LN+ using these variables was developed composed of low- (N = 2,779), intermediate- (N = 2,598), high- (N = 3,433), and very-high-risk (N = 3,418) groups; within each group the rate of LN+ was 8.7%, 48.6%, 64.9%, and 92.8%, respectively., Conclusions: This developed risk-score model, including both patient and tumor variables, can be used to calculate the risk for LN metastases in patients with GEP NETs., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022. Society of Surgical Oncology.)

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., (© 2022. Society of Surgical Oncology.)

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., (© 2021 Wiley Periodicals LLC.)

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., (© 2021 Wiley Periodicals LLC.)

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., (© 2021. Society of Surgical Oncology.)

Background: Localized gastrointestinal stromal tumors (GISTs) are rare tumors typically managed with surgery, but outcomes among octogenarians remain less studied., Methods: Octogenarian patients with stage I-III gastric GISTs were identified from the National Cancer Database and classified by resection status. Cox regression and Kaplan-Meier survival analyses analyzed 5-year overall survival (OS). Ninety-day mortality was analyzed following 1:1 propensity score matching., Results: Identified octogenarians (N = 949) who underwent resection (N = 632) had improved adjusted OS (71% vs 59.6%, HR 0.75, p 0.049) as compared to non-resected patients. Following matching, 90-day mortality was 5.7% and 11% in resected and non-resected patients (p 0.052), respectively. After exclusion of patients with 90-day mortality, resected patients maintained an OS advantage (77.3% vs 71.1%, HR 0.64, p 0.028)., Conclusions: The majority of octogenarians with localized gastric GIST are treated with surgery portending improved survival but an appreciable mortality, suggesting a necessity for careful selection of older patients for surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The risk of postoperative hungry bone syndrome after parathyroidectomy for secondary hyperparathyroidism of renal origin may alter the course of treatment, including the hospital length of stay and readmission rates. We sought to identify additional patient or hospital factors that might contribute to hungry bone syndrome after parathyroidectomy in patients with secondary hyperparathyroidism of renal origin., Methods: Patients who underwent a parathyroidectomy for secondary hyperparathyroidism of renal origin were identified in a geographically diverse, 10-state, discharge data set. Covariates included demographic data, payer status, 31 comorbidities, and hospital characteristics. The primary outcome variable of interest was hospital length of stay. Secondary outcomes were complications and 30-day readmission., Results: Of 796 patients studied, 164 patients (20.6%) were diagnosed with hungry bone syndrome. There were no differences in the rates of hungry bone syndrome by race or number of comorbidities. The average age of hungry bone syndrome patients (45.7 years ± 13.9) was younger than that of non-hungry bone syndrome patients (50.7 ± 14.8; P < .001). Hungry bone syndrome was more common among obese patients than nonobese patients (25.0% vs 15.8%; P < .001). Parathyroid autotransplant was performed at similar rates in hungry bone syndrome and non-hungry bone syndrome patients (23.8% vs 23.1%; P = .821). Median length of stay was significantly longer for hungry bone syndrome patients (6 days, interquartile range: [4, 8] versus 3 days, interquartile range: [2-6]; P < .001). Similar 30-day readmission rates were observed (hungry bone syndrome: 41 (25%) versus non-hungry bone syndrome: 147 (23%); P = .640)., Conclusion: Hungry bone syndrome occurs in 1 of 5 patients after parathyroidectomy for secondary hyperparathyroidism of renal origin. Patients should be informed of the possibility of a relatively long (6 days) length of stay after surgery as well as the moderate possibility (>20%) of another hospitalization within the 30-day postdischarge period., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors report no relevant conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2021. Society of Surgical Oncology.)

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., (© 2021. Society of Surgical Oncology.)

Context: Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes., Objective: The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1c (HbA1c). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control., Design: A retrospective cohort study was performed (1999-2020). Wilcoxon rank-sum tests compared nonparametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HbA1c. The median study duration was 54.2 months [interquartile range (IQR) 19.0-95.1]., Setting: Tertiary academic hospital., Patients: 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR 45-67) and 56.4% (n = 203) were female., Main Outcome Measures: The primary and secondary outcomes were weight and HbA1c, respectively., Results: On multivariable MEM, norepinephrine (P < 0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (P < 0.0005) correlated when only metanephrines were included. In the surgical cohort (n = 272), normetanephrine decreased postoperatively and was inversely associated with weight (P < 0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (P < 0.0005) directly correlated with HbA1c., Conclusion: Plasma norepinephrine and its metabolite directly correlate with HbA1c and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HbA1c despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Total gastrectomy for gastric cancer is associated with significant 30-day mortality, but this endpoint may underestimate the short-term mortality of the procedure., Methods: Retrospective analysis was performed using the National Cancer Database (2004-2015). Patients who underwent total gastrectomy for stage I to III gastric adenocarcinoma were identified and divided into cohorts based on 90-day mortality. Predictors of mortality were analyzed using multivariable logistic regression, and annual trends in mortality rates were calculated by Joinpoint Regression., Results: Of the 5,484 patients who underwent total gastrectomy, 90-day and 30-day mortality rates were 9.1% and 4.7%, respectively. Factors associated with 90-day mortality included increasing age (odds ratio 1.0, P < .001), income below the median (odds ratio 1.2, P = .039), Charlson-Deyo score ≥2 (odds ratio 1.4, P = .039), treatment at low-volume facilities (odds ratio 1.5, P < .001), N1 (odds ratio 2.0, P < .001), N2 (odds ratio 2.0, P < .001), or N3 (odds ratio 2.7, P < .001) stage disease, having <16 lymph nodes harvested (odds ratio 1.5, P < .001), and lack of treatment with chemotherapy (3.7, P < .001). Lack of health insurance (odds ratio 4.1, P = .080), and positive microscopic margins (odds ratio 1.3, P = .080) were correlated, but not significantly associated, with 90-day mortality. The 90-day mortality rate significantly declined from 14.3% in 2004 to 7.9% in 2015 (P = .006), and the 30-day mortality rate significantly declined from 7.7% in 2004 to 4.8% in 2015 (P = .009)., Conclusion: Nearly half of the deaths within 90 days after total gastrectomy for cancer occur beyond 30 days postoperative. Ninety-day mortality has improved over time, but rates remain high, suggesting the need for improved out-of-hospital postoperative care beyond 30 days., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose of Review: Primary aldosteronism (PA) is the most common cause of secondary hypertension and is significantly under-diagnosed. Delays in diagnosis and treatment can lead to cardiovascular morbidity and mortality. The goal of this study is to review the management of PA, with a focus on medical and surgical treatment outcomes., Recent Findings: PA causes cardiovascular dysfunction in excess of degree of hypertension. Adrenalectomy demonstrates a therapeutic advantage over mineralocorticoid antagonist (MRA) therapy, after controlling for degree of hypertension and subtype of PA. Higher rates of atrial fibrillation, heart failure, stroke, and incidence of chronic kidney disease are observed in subjects treated with MRAs than in subjects treated with adrenalectomy. The therapeutic benefit of surgery may reflect definitive resolution of excess aldosterone. Complete mineralocorticoid blockade may achieve similar benefit to adrenalectomy. Adrenalectomy is the most effective treatment for unilateral PA. Biomarkers for MRA therapy might inform optimal medical therapy of bilateral adrenal hyperplasia.

Background: Transfusion guidelines have been established for severe anemia, but limited data is available regarding the utility of preoperative transfusion. This study evaluates the predictive factors and relative value of preoperative transfusion in oncologic patients with moderate anemia undergoing abdominal surgery., Methods: Using the American College of Surgeons National Surgical Quality Improvement Program database, adult patients with moderate anemia (hematocrit 21-27%) who underwent non-emergent abdominal oncologic resection from 2005 to 2017 were identified. Preoperative transfusion and non-transfused patients were propensity score matched based on baseline covariates. Outcomes were compared using univariate and Poisson regression analysis., Results: Of 6222 patients, preoperative transfused (N = 1000, 16.1%) patients were more likely to have bleeding disorders (12.1% vs 6.7%, p < 0.0001) and baseline thrombocytopenia (12% vs 7.3%, p < 0.0001) and had shorter operative length (< 180 min: 69.4% vs 59.8%, p < 0.0001). After matching (N = 987/group), preoperative transfusion was associated with higher rates of intraoperative/postoperative transfusion (odds ratio 1.24, p 0.017) and surgical site infections (odds ratio 1.67, p 0.004) and longer length of stay (incidence rate ratio 1.06, p < 0.0001)., Conclusions: Preoperative transfusion is associated with increased surgical site infections and longer hospital stay and should be carefully considered in oncologic patients given the absence of improvement in outcomes.

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., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

Abstract: This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management and surveillance of metastatic and unresectable pheochromocytoma and paraganglioma held on October 2 and 3, 2019. The panelists consisted of endocrinologists, medical oncologists, surgeons, radiologists/nuclear medicine physicians, nephrologists, pathologists, and radiation oncologists. The panelists performed a literature review on a series of questions regarding the medical management of metastatic and unresectable pheochromocytoma and paraganglioma as well as questions regarding surveillance after resection. The panelists voted on controversial topics, and final recommendations were sent to all panel members for final approval., Competing Interests: T.E. discloses consulting on an advisory board for HRA Pharma and Corcept Therapeutics, and participates in institutional contracted clinical study for Merck and Co, Inc, Corcept Therapeutics, and Strongbridge Biopharma. J.R.H. discloses National Institutes of Health grant funding unrelated to this project and royalties for a book on endocrine surgery unrelated to this project. S.L.A. discloses board membership for Leica Biosystems, consults for PathAI, and has received speaker payment from Med Learning Group. P.L.M.D. discloses support to travel to North American Neuroendocrine Tumor Society, is a full-time faculty member at the University of Texas Health San Antonio, and received grant funding for other projects from the National Institutes of Health and Alex's Lemonade Stand Foundation. T.A.H. discloses consulting for Ipsen and pending grant from Advanced Accelerator Applications. P.L.K. discloses consulting for Advanced Accelerator Applications and Ipsen and has grants from Advanced Accelerator Applications, Ipsen, Brahms (Thermo Fisher Scientific), Lexicon Pharmaceuticals, and Xencor. K.P. discloses serving one time on an advisory board panel for Celgene and Eisai, both unrelated to this manuscript. D.A.P. discloses consulting honoraria from Siemens, Progenics, Bayer, Ipsen, Fusion, 511 Pharma, and Actinium, and receiving research funding from Siemens, Fusion, Nordic Nanovector, 511 Pharma, and Progenics. A.R.S. discloses being part owner of a start-up called Sanguine Diagnostics and Therapeutics and also lecturing for Novartis pending. M.C.S. discloses consulting fees from Guerbet LLC, Genentech, and Instylla, and grant funding from Guerbet LLC and Boston Scientific. The other authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2020 Wiley Periodicals LLC.)

Background: Although tumor size and mitotic rate are established prognostic factors for worse survival in patients undergoing surgical resection for gastric gastrointestinal stromal tumors, the impact of microscopic margins, or R1 resection, is not completely established., Methods: Patients who received no neoadjuvant therapy and underwent surgical resection for stage I to III gastric gastrointestinal stromal tumors were identified from the 2010 to 2013 National Cancer Database and divided into 2 cohorts, R0 and R1 resections. Cox proportional hazards ratio and Kaplan Meier survival estimates were utilized to analyze 5-y overall survival., Results: Of 2,084 patients, those with R1 resection (57, 2.7%) were more likely to have tumors >10 cm (28.1% vs 11.9%, odds ratio 3.51, P = .017) and stage III disease (26.3% vs 11.2%, odds ratio 2.26, P = .047). Although margin status was associated with higher risk tumors, it was not associated with receipt of adjuvant therapy. After multivariate Cox regression, R1 and R0 patients did not have a difference in 5-y overall survival (82.5% vs 88.6%, hazards ratio 1.26, P = .49). When stratified by stage of disease, there remained no difference in survival across all stages when comparing R1 and R0 patients., Conclusion: Positive microscopic margins are uncommon but do not appear to impact survival outcomes in patients with resected localized gastric gastrointestinal stromal tumors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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.

Purpose: The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes., Methods: The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS)., Results: From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low-moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P < .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score., Conclusion: Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Weight change offers the simplest indication of a patient's recovery after an operation. There have been no studies that have thoroughly investigated postoperative weight dynamics after pancreatectomy. The aim of this study was to define postoperative weight change after a pancreatectomy and determine factors associated with optimal and poor weight trajectories., Methods: From 2004 to 2019, 1,090 proximal (65%) and distal (35%) pancreatectomies were performed in patients with adequate data in the medical records. Patient weights were acquired preoperatively and at postoperative months 1, 3, and 12. Optimal (top quartile, weight restoration) and poor (bottom quartile, persistent weight loss) postoperative weight cohorts were identified at 1 year postoperatively., Results: The median percentage weight change 1 year postpancreatectomy was -6.6% (interquartile range: -1.4% to -12.5%), -7.8% for proximal pancreatectomy, and -4.2% for distal pancreatectomy. For most patients (interquartile range cohort), the median percentage weight change at 1, 3, and 12 months was -6.2%, -7.2%, and -6.6%. The independent factors associated with weight restoration were age <65, nonobesity (body mass index <30kg/m 2 ), receiving total parenteral nutrition/total enteral nutrition preoperatively, experiencing preoperative weight loss >10%, distal pancreatectomy, not undergoing vascular resection, and no readmission within 30 days. Conversely, persistent weight loss was associated with American Society of Anesthesiologists classes III to IV, obesity, malignancy, proximal pancreatectomy, blood loss ≥350mL, and experiencing readmission within 30 days. Focusing on pancreatic ductal adenocarcinoma (n = 372) patients, the factors associated with persistent weight loss were obesity, proximal pancreatectomy, and experiencing recurrence within 1 year; however, weight cohorts were not associated with overall survival for pancreatic ductal adenocarcinoma patients., Conclusion: These data define weight kinetics after pancreatectomy. Ultimately, postoperative weight trajectories appear to be largely predetermined but may be mitigated by limiting readmissions and complications. Clinicians should use these data to identify patients who continue to lose weight between the first and third month postoperatively with a high suspicion for the requirement of nutritional monitoring or other interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)