Factors Impacting Academic Productivity and Satisfaction of Surgeon-scientists: A Nationwide Survey.

OBJECTIVE: To identify factors related to research success for academic surgeons. SUMMARY BACKGROUND DATA: Many recognize mounting barriers to scientific success for academic surgeons, but little is known about factors that predict success for individual surgeons. METHODS: A phase 1 survey was emailed to department chairpersons at highly funded US departments of surgery. Participating chairpersons distributed a phase 2 survey to their faculty surgeons. Training- and faculty-stage exposures and demographic data were collected and compared with participant-reported measures of research productivity. Five primary measures of productivity were assessed including number of grants applied for, grants funded, papers published, first/senior author papers published, and satisfaction in research. RESULTS: Twenty chairpersons and 464 faculty surgeons completed the survey, and 444 faculty responses were included in the final analysis. Having a research-focused degree was significantly associated with more grants applied for (PhD, incidence rate ratio (IRR)=6.93; masters, IRR=4.34) and funded (PhD, IRR=4.74; masters, IRR=4.01) compared to surgeons with only clinical degrees (all P<0.01). Having a formal research mentor was significantly associated with more grants applied for (IRR=1.57, P=0.03) and higher satisfaction in research (IRR=2.22, P<0.01). Contractually protected research time was significantly associated with more grants applied for (IRR=3.73), grants funded (IRR=2.14), papers published (IRR=2.12), first/senior authors published (IRR=1.72), and research satisfaction (Odds ratio=2.15) (all P<0.01). The primary surgeon-identified barrier to research productivity was lack of protection from clinical burden. CONCLUSIONS: Surgeons pursuing research-focused careers should consider the benefits of attaining a research-focused degree, negotiating for contractually protected research time, and obtaining formal research mentorship.

Survival disparities in rural versus urban patients with pancreatic neuroendocrine tumor: A multi-institutional study from the US neuroendocrine tumor study group.

BACKGROUND: Pancreatic Neuroendocrine Tumors (PNETs) are indolent malignancies that often have a prolonged clinical course. This study assesses disparities in outcomes between PNET patients who live in urban (UA) and rural areas (RA). METHODS: A retrospective cohort study was performed using the US Neuroendocrine Tumor Study Group database. PNET patients with a home zip code recorded were included and categorized as RA or UA according to the Federal Office of Rural Health Policy. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and logistical regression. RESULTS: Of the 1176 PNET patients in the database, 1126 (96%) had zip code recorded. While 837 (74%) lived in UA, 289 (26%) lived in RA. RA patients had significantly shorter median OS following primary PNET resection (122 vs 149 months, p â€‹= â€‹0.01). After controlling for income, local healthcare access, distance from treatment center, ASA class, BMI, and T/N/M stage, living in a RA remained significantly associated with worse OS (HR 1.60, 95%CI 1.08-2.39, p â€‹= â€‹0.02). CONCLUSION: Rural patients have significantly shorter OS following PNET resection compared to their urban counterparts.

Parental Support Policies and Benefits: A Surgical Training Program Report Card of Transparency.

OBJECTIVE: This study aimed to investigate the transparency of parental benefits available to US surgical residency applicants. BACKGROUND: Medical students prioritize work-family balance in specialty selection. Those applying to surgical residency programs also place a significant value on parental leave policies when deciding where to train. However, little is known about the amount of information that surgical training programs publicly offer to potential applicants regarding family support policies. METHODS: Publicly available websites for 264 general surgery training programs were accessed to determine the availability of information on parental benefits. Twenty-six "items of transparency" included types of leave, contract flexibility, salary, lactation, and childcare support. Programs with fewer than the median items of transparency were contacted to inquire about additional public resources. Academic programs were stratified by their associated medical school rankings in the US News & World Report. RESULTS: A total of 144 (54%) programs were academic and 214 (81.4%) had male program directors. The median number of items of transparency was 8 (29.6%). Of the 131 programs contacted, 33 (25.9%) replied, and 2 (6.1%) improved their transparency score. Academic programs associated with medical schools in the upper third of the rankings were more likely to have ≥8 items of transparency (70.8% vs. 45.6%; P =0.002). In the adjusted analysis, academic programs [odds ratio (OR): 3.44, 95% confidence interval (95% CI): 1.87-6.34], those with female program directors (OR: 2.09, 95% CI: 1.01-4.33), and those located in the Western (OR: 3.13, 95% CI: 1.31-7.45) and Southern (OR: 2.45, 95% CI: 1.21-4.98) regions of the country were more likely to have ≥8 items of transparency. CONCLUSIONS: There are significant deficits in publicly available information related to parental benefits for many surgical training programs, which may impact applicants' decision making. Attracting the most talented candidates requires programs to create and share policies that support the integration of professional and personal success.

Colon epithelial cell TGFß signaling modulates the expression of tight junction proteins and barrier function in mice.

Defective barrier function is a predisposing factor in inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Although TGFß signaling defects have been associated with IBD and CAC, few studies have examined the relationship between TGFß and intestinal barrier function. Here, we examine the role of TGFß signaling via SMAD4 in modulation of colon barrier function. The Smad4 gene was conditionally deleted in the intestines of adult mice and intestinal permeability assessed using an in vivo 4 kDa FITC-Dextran (FD4) permeability assay. Mouse colon was isolated for gene expression (RNA-sequencing), Western blot, and immunofluorescence analysis. In vitro colon organoid culture was utilized to assess junction-related gene expression by qPCR and transepithelial resistance (TER). In silico analyses of human IBD and colon cancer databases were performed. Mice lacking intestinal expression of Smad4 demonstrate increased colonic permeability to FD4 without gross mucosal damage. mRNA/protein expression analyses demonstrate significant increases in Cldn2/Claudin 2 and Cldn8/Claudin 8, and decreases in Cldn3, Cldn4, and Cldn7/Claudin 7 with intestinal SMAD4 loss in vivo without changes in Claudin protein localization. TGFß1/BMP2 treatment of polarized SMAD4+ colonoids increases TER. Cldn2, Cldn4, Cldn7, and Cldn8 are regulated by canonical TGFß signaling, and TGFß-dependent regulation of these genes is dependent on nascent RNA transcription (Cldn2, Cldn4, Cldn8) but not nascent protein translation (Cldn4, Cldn8). Human IBD/colon cancer specimens demonstrate decreased SMAD4, CLDN4, CLDN7, and CLDN8 and increased CLDN2 compared with healthy controls. Canonical TGFß signaling modulates the expression of tight junction proteins and barrier function in mouse colon.NEW & NOTEWORTHY We demonstrate that canonical TGFß family signaling modulates the expression of critical tight junction proteins in colon epithelial cells, and that expression of these tight junction proteins is associated with maintenance of colon epithelial barrier function in mice.

Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. METHODS: A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test. RESULTS: Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. CONCLUSION: In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs. METHODS: A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS). RESULTS: High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04). CONCLUSION: High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. PATIENTS AND METHODS: A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). RESULTS: The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006]. CONCLUSIONS: Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group.

BACKGROUND: Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection. METHODS: A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression. RESULTS: Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia. CONCLUSION: PRBC transfusion is associated with worse survival for patients undergoing PNET resection.

Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group.

BACKGROUND: Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined. METHODS: Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined. RESULTS: Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n = 158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p < 0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size ≥ 2 cm (odds ratio [OR] 6.6; p < 0.001), proximal location (OR 2.5; p < 0.001), moderate versus well-differentiation (OR 2.1; p = 0.006), and Ki-67 ≥ 3% (OR 3.1; p < 0.001). LN metastases were also present in tumors without these risk factors: < 2 cm (9%), distal location (19%), well-differentiated (23%), and Ki-67 < 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p = 0.198; seven or more LNs: 67% vs. 86%; p = 0.002). CONCLUSIONS: Tumor size ≥ 2 cm, proximal location, moderate differentiation, and Ki-67 ≥ 3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.

Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection.

BACKGROUND: The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized. METHODS: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome. RESULTS: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative-intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease-free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64-1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis. CONCLUSION: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.

Prognostic Role of Lymph Node Positivity and Number of Lymph Nodes Needed for Accurately Staging Small-Bowel Neuroendocrine Tumors.

Importance: Little information is available regarding the minimum number of lymph nodes needed to accurately stage patients when performing a mesenteric lymphadenectomy for small-bowel neuroendocrine tumors. Objectives: To determine the prognostic role of lymph node positivity and the ideal number of lymph nodes for accurately staging patients with small-bowel neuroendocrine tumors. Design, Setting, and Participants: This case series from the US Neuroendocrine Tumor Study Group, a collaboration among 8 US-based, academic tertiary care referral centers, obtained demographic, perioperative, and pathologic data from the group's database, Social Security Death Index, and publicly available obituaries. All patients in these institutions with small-bowel neuroendocrine tumors who underwent curative-intent surgical resection of a primary tumor between January 1, 2000, and December 31, 2015, were included (n = 199). Patients with duodenal or ampullary tumors, other nonneuroendocrine concurrent malignant neoplasms, mortality of fewer than 30 days after the surgical procedure, and distant metastatic disease were excluded. Data analysis was conducted from September 1, 2017, to December 1, 2017. Main Outcomes and Measures: Primary study outcome was recurrence-free survival. Hypothesis was generated after data collection and data entry into the US Neuroendocrine Tumor Study Group database. Results: Of the 199 patients included, 112 (56.3%) were male and 87 (43.7%) female with a mean (SD) age of 60.3 (12.5) years and a mean (SD) body mass index of 29.5 (6.0). One hundred fifty-four patients (77.4%) had lymph node-positive disease. No difference in 3-year recurrence-free survival was found between patients with lymph node-positive and lymph node-negative disease. Patients with 4 positive lymph nodes had a worse 3-year recurrence-free survival compared with those with 1 to 3 or 0 positive lymph nodes (81.6% vs 91.4% vs 92.1%; P = .01). When examining patients with fewer than 8 resected lymph nodes, no difference in 3-year recurrence-free survival was observed among patients with 4 or more, 1 to 3, or 0 positive lymph nodes (100% vs 93.8% vs 91.7%; P = .87). Retrieval of 8 or more lymph nodes, however, accurately discriminated patients with 4 or more, 1 to 3, or 0 positive lymph nodes (3-year recurrence-free survival: 79.9% vs 89.6% vs 92.9%; P = .05). Conclusions and Relevance: The findings from this study suggest that, for patients undergoing curative-intent resection of small-bowel neuroendocrine tumors, accurate lymph node staging requires a minimum of 8 lymph nodes for examination, and 4 or more positive lymph nodes are associated with decreased 3-year recurrence-free survival compared with 1 to 3 or 0 positive lymph nodes; a thorough regional lymphadenectomy may be critical for accurate staging and management of this disease.

Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms.

INTRODUCTION: Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known. METHODS: We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group. RESULTS: Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n = 223, 67.4%), GI bleeding (n = 54, 16.3%), GI obstruction (n = 49, 14.8%), and biliary obstruction (n = 22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4 weeks of diagnosis. The median overall survival was 110.4 months, and operative intent predicted survival (p < 0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5 months) compared to debulking (89.2 months), or palliative resection (50.0 months; p < 0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p = 0.006), foregut NET (5.62, p = 0.042), major complication (4.91, p = 0.001), and high tumor grade (11.2, p < 0.001). The conditional survival for patients who lived past 1 year was 119 months. CONCLUSIONS: Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.

Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer.

Background & Aims: Chronic inflammation is a predisposing condition for colorectal cancer. Many studies to date have focused on proinflammatory signaling pathways in the colon. Understanding the mechanisms that suppress inflammation, particularly in epithelial cells, is critical for developing therapeutic interventions. Here, we explored the roles of transforming growth factor ß (TGFß) family signaling through SMAD4 in colonic epithelial cells. Methods: The Smad4 gene was deleted specifically in adult murine intestinal epithelium. Colitis was induced by 3 rounds of dextran sodium sulfate in drinking water, after which mice were observed for up to 3 months. Nontransformed mouse colonocyte cell lines and colonoid cultures and human colorectal cancer cell lines were analyzed for responses to TGFß1 and bone morphogenetic protein 2. Results: Dextran sodium sulfate treatment was sufficient to drive carcinogenesis in mice lacking colonic Smad4 expression, with resulting tumors bearing striking resemblance to human colitis-associated carcinoma. Loss of SMAD4 protein was observed in 48% of human colitis-associated carcinoma samples as compared with 19% of sporadic colorectal carcinomas. Loss of Smad4 increased the expression of inflammatory mediators within nontransformed mouse colon epithelial cells in vivo. In vitro analysis of mouse and human colonic epithelial cell lines and organoids indicated that much of this regulation was cell autonomous. Furthermore, TGFß signaling inhibited the epithelial inflammatory response to proinflammatory cytokines. Conclusions: TGFß suppresses the expression of proinflammatory genes in the colon epithelium, and loss of its downstream mediator, SMAD4, is sufficient to initiate inflammation-driven colon cancer. Transcript profiling: GSE100082.

Role of Additional Organ Resection in Adrenocortical Carcinoma: Analysis of 167 Patients from the U.S. Adrenocortical Carcinoma Database.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer. This report describes factors and outcomes associated with resection of extra-adrenal organs en bloc during index adrenalectomy. METHODS: Patients who underwent ACC resection for non-metastatic disease from 1993 to 2014 at 13 participating institutions of the US-ACC Group were included in the study. Factors associated with en bloc resection were assessed by uni- and multivariate analysis. The primary end point was overall survival. RESULTS: In this study, 167 patients were included and categorized as adrenalectomy with en bloc resection (AdEBR) if they had extra-adrenal organs removed or adrenalectomy (Ad) if they did not. The demographics were similar between the AdEBR (n = 68, 40.7%) and Ad groups, including age, gender, race, American Society of Anesthesiology (ASA) class, and body mass index (BMI). The AdEBR group had larger tumors (13 vs. 10 cm), more open operations (97.1 vs. 63.6%), and more lymph node dissections (LNDs) (36.8 vs. 12.1%). The most common organs removed were kidney (55.9%), liver (27.9%), and spleen (23.5%). Multiple organs were removed in 38.2% (n = 26) of the patients. Margin-negative resections were similar between the two groups. In the multivariate Cox regression adjusted for T and N stages, LND, margin, size, and hormone hypersecretion, en bloc resection was not associated with improved survival (hazard ratio [HR], 1.42; p = 0.323). CONCLUSION: The study findings validated current practice by showing that en bloc resection should occur at index adrenalectomy for ACC when a T4 lesion is suspected pre- or intraoperatively, or when it is necessary to avoid tumor rupture. However, in this study, when a negative margin resection was otherwise achieved, removal of extra-adrenal organs en bloc was not associated with additional survival benefit.