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.

Sex differences and racial/ethnic disparities in the presentation and treatment of medullary thyroid cancer.

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 â€‹cm were more likely in men (vs. women: OR 2.47, p â€‹< â€‹0.001) and Hispanic patients (vs. White patients: OR 1.52, p â€‹= â€‹0.001). Non-White patients were more likely to have distant metastases (Black: OR 1.63, p â€‹= â€‹0.002; Hispanic: OR 1.44, p â€‹= â€‹0.038) and experienced longer time to surgery (Black: HR 0.66, p â€‹< â€‹0.001; Hispanic: HR 0.71, p â€‹< â€‹0.001). Black patients were less likely to undergo guideline-concordant surgery (OR 0.70, p â€‹= â€‹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.

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.

Adrenalectomy approach and outcomes according to surgeon volume.

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 â€‹= â€‹3) performed 394, while low-volume surgeons (n â€‹= â€‹12) performed 82. High-volume surgeons more frequently operated for pheochromocytoma (19% vs. 16%, p â€‹< â€‹0.001) and less frequently for metastasis (6.4% vs. 23%, p â€‹< â€‹0.001), more frequently used laparoscopy (95% vs. 80%, p â€‹< â€‹0.001), and had lower operative supply costs ($1387 vs. $1,636, p â€‹= â€‹0.037). Additionally, laparoscopic adrenalectomy was associated with shorter length of stay (-3.43 days, p â€‹< â€‹0.001), lower hospitalization costs (-$72,417, p â€‹< â€‹0.001), and increased likelihood of discharge to home (OR 17.03, p â€‹= â€‹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.

Technique and Outcomes of Concomitant Aortic and Caval Resection and Reconstruction for Retroperitoneal Tumors.

BACKGROUND: Major vascular involvement is often considered a contraindication to resection of malignant tumors, but in highly selected patients, it can be performed safely, with results that are highly dependent upon the tumor biology. Resection of both the aorta and inferior vena cava (IVC) is a rare undertaking, requiring both favorable tumor biology and a patient fit for a substantial surgical insult; nevertheless, it provides the possibility of a cure. METHODS: Patients requiring resection and reconstruction of both the aorta and IVC from 2009 through 2019 at 2 university medical centers were included. Patient characteristics, operative technique, and outcomes were retrospectively collected. RESULTS: We identified 9 patients, all with infrarenal reconstruction or repair of the aorta and IVC. All cases were performed with systemic heparinization and required simultaneous aortic and caval cross-clamping for tumor resection. No temporary venous or arterial bypass was used. Since arterial reperfusion with the IVC clamped was poorly tolerated in 1 patient, venous reconstruction was typically completed first. Primary repair was performed in 1 patient, while 8 required replacements. In 2 patients, aortic homograft was used for replacement of both the aortoiliac and iliocaval segments in contaminated surgical fields. In the remaining 6, Dacron was used for arterial replacement; either Dacron (n = 2) or polytetrafluoroethylene (n = 4) were used for venous replacement. Patients were discharged after a median stay of 8 days (range: 5-16). At median follow-up of 17 months (range 3-79 months), 2 patients with paraganglioma and 1 patient with Leydig cell carcinoma had cancer recurrences. Venous reconstructions occluded in 3 patients (38%), although symptoms were minimal. One patient presented acutely with a thrombosed iliac artery limb and bilateral common iliac artery anastomotic stenoses, treated successfully with thrombolysis and stenting. CONCLUSIONS: Patients with tumor involving both the aorta and IVC can be successfully treated with resection and reconstruction. En bloc tumor resection, restoration of venous return before arterial reconstruction, and most importantly, careful patient selection, all contribute to positive outcomes in this otherwise incurable population.

The use and costs of same-day surgery versus overnight admission for total thyroidectomy: A multi-state, all-payer analysis.

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.

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.

Tricks of the trade: Techniques for preoperative localization in reoperative parathyroidectomy.

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.

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.

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

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

How low is too low? Intraoperative parathyroid hormone decline in normohormonal primary hyperparathyroidism.

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.

Simulated data-driven hospital selection for surgical treatment of well-differentiated thyroid cancer in older adults.

BACKGROUND: Thyroid surgery at high-quality hospitals is associated with fewer complications. We evaluated the impact of referring older adults with thyroid cancer to higher-performing local hospitals. METHODS: We performed a simulation study of Surveillance, Epidemiology, and End Results-Medicare patients, aged ≥66 years, who underwent a thyroidectomy for well-differentiated thyroid cancer (2013-2017). An 80% sample was used to calculate each hospital's risk-standardized 30-day serious adverse event rate, dividing hospitals into quartiles by performance. Hospitals located ≤30 miles of the remaining 20% of patients were compared, and 30-day serious adverse event rates and costs were simulated as if patients were treated at higher-quality hospitals using logistic regression with each alternative hospital's fixed-effect. RESULTS: We identified 8,946 patients who underwent thyroid resection at 843 hospitals. Average risk-adjusted serious adverse event rates ranged from 13.9% to 52.9% between quartile 1 and 4 hospitals (P < .001). We identified higher-quality hospitals for 43.7% of patients. Simulating care at the best local hospital reduced predicted serious adverse event rates from 25.6% (95% confidence interval, 24.7-26.4) to 16.2% (95% confidence interval, 15.5-16.8; P < .001), while modestly lowering average costs from $12,883 (95% confidence interval, 12,500-13,267) to $12,679 (95% confidence interval, 12,304-13,056; P = .029). CONCLUSION: Simulated care at higher-performing hospitals decreased serious adverse event rates after thyroid resection. Optimizing hospital selection may reduce postoperative morbidity without compromising preferences for local treatment.

Case presentation of 8-year follow up of recurrent malignant duodenal Insulinoma and lymph node metastases and literature review of malignant Insulinoma management.

BACKGROUND: Insulinoma is an uncommon insulin-secreting neuroendocrine tumor that presents with severe recurrent hypoglycemia. Although cases of extrapancreatic insulinomas have been reported, the majority of insulinomas occur in the pancreas. The number of reported cases of ectopic insulinomas with follow-up assessments is limited and they do not report disease recurrence. The current report presents the first documented case of recurrent extrapancreatic insulinoma with 8 years of follow-up, provides relevant literature review, and proposes surveillance and treatment strategies. CASE PRESENTATION: We describe an insulinoma localized in the duodenal wall of a 36-year-old female who presented in 2013 with weight gain and Whipple's triad and was successfully managed with duodenotomy and enucleation. She presented again in 2017 with recurrent Whipple's triad and was found to have metastatic disease localized exclusively to peripancreatic lymph nodes. Primary pancreatic insulinoma was not evident and her hypoglycemia resolved following lymph node dissection. Eight years after initial presentation continuous glucose monitoring (CGM) showed a trend for euglycemia, and PET-CT Gallium 68 DOTATATE scan evaluation indicated absence of recurrent disease. CONCLUSION: Insulinomas are rare clinical entities and extrapancreatic insulinomas are particularly uncommon. Follow-up evaluation and treatment strategies for ectopic insulinoma recurrence presents a significant clinical challenge as the condition has hitherto remained undescribed in the literature. Available evidence in the literature indicates that lymph node metastases of intrapancreatic insulinomas likely do not change prognosis. Given the absence of long-term data informing the management and monitoring of patients with extrapancreatic insulinoma, we suggest patient education for hypoglycemic symptoms, monitoring for hypoglycemia with CGM, annual imaging, and a discussion with patients regarding treatment with octreotide or alternative somatostatin receptor analog therapies.

Validated Risk-Score Model Predicting Lymph Node Metastases in Patients with Non-Functional Gastroenteropancreatic Neuroendocrine Tumors.

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.

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.

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.